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11056	What is a trust? What are the different types of trusts?	[ { "docid": "449081", "text": "\"From a more technical point of view, a trust is a legal relationship between 3 parties: Trusts can take many forms. People setup trusts to ensure that property is used in a specific way. Owning a home with a spouse is a form of a trust. A pension plan is a trust. Protecting land from development often involves placing it in trust. Wealthy people use trusts for estate planning for a variety of reasons. There's no \"\"better\"\" or \"\"best\"\" trust on a general level... it all depends on the situation that you are in and the desired outcome that you are looking for.\"", "title": "" }, { "docid": "534290", "text": "Trusts are a way of holding assets with a specific goal in mind. At its simplest, a trust can be used to avoid probate, a sometimes lengthy process in which a will is made public along with the assets bequeathed. A trust allows for fast transfer and no public disclosure. Depending on the current estate tax laws (the death tax) a trust can help preserve an estate exemption. e.g. Say the law reverts back to a $1M exemption. Note, this is $1M per deceased person, not per beneficiary. My wife and I happened to have assets of exactly $2M, and I die tomorrow. Now she has $2M, and when she passes, the estate has that $2M and estate taxes are based on this total, $1M fully taxed. But - If we set up trusts, that first million can be put into trust on my death, the interest and some principal going to the surviving spouse each year, but staying out of the survivor's estate. Second spouse dies, little or no tax due. This is known as a bypass trust. Another example is a spendthrift trust. Say, hypothetically, my sister in law can't save a nickel to save her life. Spends every dime and then some. So the best thing my mother in law can do to provide for her is to leave her estate in trust with specific instructions on how to distribute some percent each year. This is not a tax dodge of any kind, it's strictly to protect the daughter from her own irresponsibility. A medical needs trust is a variant of the above. It can provide income to a disabled person without impacting their government benefits adversely. This scratches the surface, illustrating how trusts can be used, there are more variation on this, but I believe it covers the basics. With the interest in this topic, I'm adding another issue where the trust can be useful. In my article On my Death, Please, Take a Breath I described how an inherited IRA was destroyed by ignorance. The beneficiary, fearing the stock market, withdrew it all and was nailed by taxes. He was on social security and no other income, so by taking small withdrawals each year would have had nearly no tax due. (and could have avoided 'market' risk by selling within the IRA and buying treasuries or CDs.) He didn't need a trust of course, just education. The deceased, his sister, might have used a Trust to manage the IRA and enforce limited withdrawals. Mixing IRAs and trust is complex, but the choice between a $2000 expense to create a trust or the $40K tax bill he got is pretty clear to me. He took pride in having sold out as the market soon tanked, but he could have avoided the tax loss as well. He was confusing the account (In this case an IRA, but it could have been a 401(k) or other retirement account) with the investments it contained. One can, and should, keep the IRA in tact, and simply adjust the allocation according to one's comfort level. Note - Inheritance tax laws change frequently, and my answer above was an attempt to be generic. The current (2014) code allows $5.34M to be left by one decedent with no estate tax.", "title": "" }, { "docid": "31182", "text": "A trust is a financial arrangement to put aside money over a period of time (typically years), for a specific purpose to benefit someone. Two purposes of trusts are 1) providing for retirement and 2) providing for a child or minor. There are three parties to a trust: 1) A grantor, the person who establishes and funds a trust. 2) A beneficiary, a person who receives the benefits. 3) a trustee, someone who acts in a fiduciary capacity between the grantor and beneficiary. No one person can be all three parties. A single person can be two of out those three parties. A RETIREMENT trust is something like an IRA (individual retirement account). Here, a person can be both the grantor (contributor) to the IRA, and the beneficiary (a withdrawer after retirement). But you need a bank or a broker to act as a fiduciary, and to handle the reporting to the IRS (Internal Revenue Service). Pension plans have employers as grantors, employees as beneficiaries, and (usually) a third party as trustee. A MINORS' trust can be established under a Gift to the Minors' Act, or other trust mechanisms, such as a Generation Skipping Trust. Here, a parent may be both grantor and trustee (although usually a third party is a trustee). A sum of money is put aside over a period of years for the benefit of a minor, for a college education, or for the minor's attaining a certain age: a minimum of 18, sometimes 21, possibly 25 or even older, depending on when the grantor feels that the minor is responsible enough to handle the money.", "title": "" } ]	[ { "docid": "291214", "text": "I'm answering your second and third point. For first point it depends on case by case basis from which organization you are opening your trust. Trust Account are of different type: To earn interest you account should be of below type. Interest in possession trusts and Income Tax Trustees are responsible for declaring and paying Income Tax on income received by the trust. They do this on a Trust and Estate Tax Return each year. There are different rates depending on the type of income - as shown below. Type of income Income Tax rate 2014 to 2015 tax year Rent, trading and savings 20% (basic rate) UK dividends (such as income from stocks and shares) 10% (dividend ordinary rate)", "title": "" }, { "docid": "24883", "text": "\"I just wanted to give you a different perspective, as I own a house (purchased with a mortgage), with my girlfriend. I think it can be done safely and fairly, but you do need to involve legal help to do it right. There really is nothing to be terrified about, the extra cost to set this up was almost irrelevant in the bigger picture of legal costs around purchasing and the documents describing the ownership scheme are quite straightforward. Maybe it's a UK thing, but it seems rather commonplace here. We've chosen to hold this as \"\"tenants in common\"\" and use a trust deed for this when we purchased. We had a solicitor write the trust deed and it clearly states what percentage of the house is owned by either party and exactly what the steps would be taken, should we decide to end the trust (e.g. in case of a split-up). This includes things like the right to buy out the other person before selling on the market etc. We also had to make wills separately to indicate what should happen with our percentage of the property in case one of us died as with this type of ownership it doesn't automatically go to the other person. Finally we're both on the mortgage, which I guess is the main difference versus your situation. But again, you could get legal advice as to how this should best be handled.\"", "title": "" }, { "docid": "464777", "text": "\">Nazis weren't socialist The National Socialist Party - that's what Nazis is the shortened form of in German. >Just because they had socialist in their name doesn't mean they were socialist. So then the \"\"Democrats\"\" doesn't mean they're democratic, and we'll vote the same type of people in again then? I mean, if we can't trust what the party name is, we might end up voting them in again under a different name.\"", "title": "" }, { "docid": "81530", "text": "\"Anytime you do work without any payment until the work is complete, you are effectively extending credit to the party receiving your service. How much credit you are willing to extend will vary greatly, depending on the amount and the trustworthiness of the party. For example, if you are charging $50 for something, you probably won't bother to collect money upfront, whereas if you are charging $5,000 you probably would collect some upfront. But if the party you are working for is a large financially sound company, the number may be even much higher than $5K as you can trust you will be paid. Obviously there are many factors that go into how much credit you are willing to extend to your customer. (This is why credit reports exist for banks to determine how much credit to extend to you.) As for the specific case you are asking about, which may be classified as a decent amount of work for a small business, I would default to having a written scope of work, a place in the document for both parties to sign, and specify 50% upfront payment and 50% payment at completion. When you receive the signed document and the upfront payment (and possibly even after the check clears), you begin work. I would call this my \"\"default contract\"\" and adjust according to your needs depending on the size of the job and the trustworthiness of the customer. As for your question about how to deposit the check, that depends on what type of entity you are. If you are a sole proprietor you should ask for the checks to be made out to you. If you are a business then the checks should be made out to your business name. You don't need \"\"in trust\"\" or anything similar because your customer, after paying the upfront fee, must trust that you will do the work you promise to do, just like you have to trust that after completing the work you will receive the final payment. This is the reason the default is 50% before and after. Both parties are risking (roughly) the same amount. Tip: having done the \"\"default\"\" contract many times in my career, both as a sole proprietor and a business owner, I can assure you there is a big difference between a potential customer agreeing to something in advance, and actually writing a check. The upfront payment definitely helps weed out those that were never going to end up paying you, even if their intentions were good. Tip 2: be as specific as possible as to what the scope of work will include. If you don't, particularly with software, they'll be adding feature after feature and expecting it to be \"\"included\"\".\"", "title": "" }, { "docid": "40158", "text": "\"This is another semantics question. Again what matters is how the words are commonly used, as the usage came about long before the technical definitions. In this case, when people say \"\"mutual fund,\"\" they are often including both unit investment trusts and closed end funds. Despite the labels the SEC has given in order to differentiate them, I'd say it's common (typical) practice to think of a closed-end fund as a type of mutual fund, rather than a different category altogether. That's the way I've seen it used, anyway.\"", "title": "" }, { "docid": "472340", "text": "like I said to the others do a remind me. I am not trying to hate on you or your views but facebook is not the future not even close they won;t survive because the vision of facebook is heavily flawed. Also GoPro being worth HALF what is with in 5 years only shows your lack of research into the company and to what I said. I also said that the money I made was essentially a drop in the bucket of what I wanted to invest but I held back heavily because of the type of companies they are and what the stocks show. The fact I made what I did on what little i put in is, well awesome. No I am not a billionaire but I am rather good at picking short and middle to long term well and have done well with it. My only fault is I don't trust my own judgement enough. I am sorry you think Snap Chat is a bad long term investment because in 5 years it will be over 100 a share. I don't expect you to take or trust the advice from a random person online but you talk like you actually know which you don't and that is ok. I just gave my opinion which I have zero doubt will pan out but that is the beauty of it!", "title": "" }, { "docid": "80464", "text": "A 'bailout' is money from the government to keep open a business that is no longer viable and by rights deserves to fail. What happened in this case was different. All banks rely on the overnight bank lending market for liquidity. It is the grease that oils the wheels of international banking. That is not a sign of weakness or recklessness. It is just standard banking practice. In 2008, during the failure of Bear Stearns and the Lehman Shock the overnight lending market simply stopped operating as nobody knew who they could trust and as a result nobody trusted anybody. Something needed to temporarily replace this overnight lending until the crisis was over. This is what that cash infusion was. It was not a bailout.", "title": "" }, { "docid": "146277", "text": "\"Is this legal? Why not? But you might have trouble deducting losses on your taxes, especially if you sell to someone related to you in some way (which is indeed what you're doing). See the added portion below regarding dealing with \"\"related person\"\" (which a sibling is). The state of Maryland has a transfer/recordation tax of 1.5% for each, the buyer and seller. Would this be computed on the appraised or sale value? You should check with the State. In California property taxes are assessed based on sale value, but if the sale value is bogus the assessors have the right to recalculate. Since you're selling to family, the assessors will likely to intervene and set a more close to \"\"fair market\"\" value on the transaction, but again - check the local law. Will this pose any problem if the buyer needs financing? Likely, banks will be suspicious.Since you're giving a discount to your sibling, it will likely not cause a problem for financing. If it was an unrelated person getting such a discount, it would likely to have raised some questions. Would I be able to deduct a capital loss on my tax return? As I said - it may be a problem. If the transaction is between related people - likely not. Otherwise - not sure. Check with a professional tax adviser (EA or CPA licensed in Maryland). You mentioned in the comment that the buyer is a sibling. IRS Publication 544 has a list of what is considered \"\"related person\"\", and that includes siblings. So the short answer is NO, you will not be able to deduct the loss. The tax treatment is not trivial in this case, and I suggest to have a professional tax adviser guide you on how to proceed. Here's the definition of \"\"related person\"\" from the IRS pub. 544: Members of a family, including only brothers, sisters, half-brothers, half-sisters, spouse, ancestors (parents, grandparents, etc.), and lineal descendants (children, grandchildren, etc.). An individual and a corporation if the individual directly or indirectly owns more than 50% in value of the outstanding stock of the corporation. Two corporations that are members of the same controlled group as defined in section 267(f) of the Internal Revenue Code. A trust fiduciary and a corporation if the trust or the grantor of the trust directly or indirectly owns more than 50% in value of the outstanding stock of the corporation. A grantor and fiduciary, and the fiduciary and beneficiary, of any trust. Fiduciaries of two different trusts, and the fiduciary and beneficiary of two different trusts, if the same person is the grantor of both trusts. A tax-exempt educational or charitable organization and a person who directly or indirectly controls the organization, or a member of that person's family. A corporation and a partnership if the same persons own more than 50% in value of the outstanding stock of the corporation and more than 50% of the capital interest or profits interest in the partnership. Two S corporations if the same persons own more than 50% in value of the outstanding stock of each corporation. Two corporations, one of which is an S corporation, if the same persons own more than 50% in value of the outstanding stock of each corporation. An executor and a beneficiary of an estate unless the sale or exchange is in satisfaction of a pecuniary bequest. Two partnerships if the same persons directly or indirectly own more than 50% of the capital interests or profits interests in both partnerships. A person and a partnership if the person directly or indirectly owns more than 50% of the capital interest or profits interest in the partnership.\"", "title": "" }, { "docid": "539752", "text": "\"I am not a lawyer, and I am assuming trusts in the UK work similar to the way they work in the US... A trust is a legally recognized entity that can act in business transactions much the same way as a person would (own real property, a business, insurance, investments, etc.). The short answer is the trust is the owner of the property. The trust is established by a Grantor who \"\"funds\"\" the trust by transferring ownership of items from him or herself (or itself, if another trust or business entity like a corporation) to the trust. A Trustee is appointed (usually by the Grantor) to manage the trust according to the conditions and terms specified in the trust. A Trustee would be failing in their responsibility (their fiduciary duty) if they do not act in accordance with the purposes of the trust. (Some trusts are written better than others, and there may or may not be room for broad interpretation of the purposes of the trust.) The trust is established to provide some benefit to the Beneficiary. The beneficiary can be anyone or anything, including another trust. In the US, a living trust is commonly used as an estate planning tool, where the Grantor, Trustee, and Beneficiary are the same person(s). At some point, due to health or other reasons, a new trustee can be appointed. Since the trust is a separate entity from the grantor and trustee, and it owns the assets, it can survive the death of the grantor, which makes it an attractive way to avoid having to probate the entire estate. A good living trust will have instructions for the Trustee on what to do with the assets upon the death of the Grantor(s).\"", "title": "" }, { "docid": "203298", "text": "My possible new job requires me to do dfast and ccar among others. A few questions 1) My background is public accounting and tax. I noted that these jobs requires experience from public firms. My past experience has nothing to do with banking. Any reasons? I have been reading up dfast in the past week and it seems they trust me to pick up fast. Another job ad from another bank indicates the same thing. 2) What type of job this is under? I tried risk analyst but quite a lot of times the results are quite different from what my job is. 3) What is the job outlook? My eventual plan is to a more data analyst role and/or job opportunities in EU. Currently in EA/SEA market. 4) Any programming language should I learn to speed up data extraction? I will be learning either python/r. And will surface 3 do? My current laptop is not working and the repair shop indicates the costs of repairing doesnt worth it.", "title": "" }, { "docid": "152709", "text": "\"Members of the Federal Reserve System keep track of what money a bank has (if it's not in the vault), who owns what shares of stock, who owns what bond, etc. The part of the Federal Reserve System that tracks stock ownership is the Depository Trust Company (DTC). They have a group of subsidiaries that settle various types of security transactions. DTC is a member of the U.S. Federal Reserve System, a limited-purpose trust company under New York State banking law and a registered clearing agency with the Securities and Exchange Commission. There's lots of information on their website describing this process. DTCC's subsidiary, The Depository Trust Company (DTC), established in 1973, was created to reduce costs and provide clearing and settlement efficiencies by immobilizing securities and making \"\"book-entry\"\" changes to ownership of the securities. DTC provides securities movements for NSCC's net settlements1, and settlement for institutional trades (which typically involve money and securities transfers between custodian banks and broker/dealers), as well as money market instruments. Black pools are trades done where the price is not shared with the market. But the DTC is the one who keeps track of who owns which shares. They have records of all net transactions2. The DTC is the counterparty for transactions. When stock moves from one entity to another the DTC is involved. As the central counterparty for the nation's major exchanges and markets, DTCC clears and settles virtually all broker-to-broker equity 1. This is the link that shows that settlements are reported on a \"\"net basis\"\". 2. If broker A sells 1000 shares of something to broker B at 8 and then five minutes later broker B sells the 1000 shares back to A, you cannot be sure that that total volume will be recorded. No net trading took place and there would be fees to pay for no reason if they reported both trades. Note: In dark pool trading quite often the two parties don't know each other. For shares (book-keeping records) to be exchanged it has to be done through a Clearing House.\"", "title": "" }, { "docid": "116865", "text": "\"They pretty much already have what you are looking for. They are called Unit Investment Trusts. The key behind these is (a) the trust starts out with a fixed pool of securities. It is completely unmanaged and there is no buying or selling of the securities, (b) they terminate after a fixed period of time, at which time all assets are distributed among the owners. According to Investment Company Institute, \"\"securities in a UIT are professionally selected to meet a stated investment objective, such as growth, income, or capital appreciation.\"\" UITs sell a fixed number of units at one-time public offering. Securities in a UIT do not trade actively, rather, UITs use a strategy known as buy-and-hold. The UIT purchases a certain amount of securities and holds them until its termination date. Holdings rarely change throughout the life of the trust so unit holders know exactly what they're investing in, and the trust lists all securities in its prospectus. Unit trusts normally sell redeemable units - this obligates the trust to re-purchase investor's units at their net asset value at the investors request.\"", "title": "" }, { "docid": "194167", "text": "\"If wire transfer through your bank does not work then perhaps one of the more popular money transfer services may be what you are looking for such as MoneyGram or Western Union. Now these rely on a trusted \"\"registered\"\" third party to do the money transfer so you need to make sure that you are working with a legitimate broker. Each money transfer service has a site that allows you to perform the search on registered parties around your area. There are certain fees that are sometimes applied due to the amount being transferred. All of these you will want to do some detailed research on before you make the transfer so that you do not get scammed. I would suggest doing a lot of research and asking people that you trust to recommend a trusted broker. I have not personally used the services, but doing a quick search brought many options with different competitive conversion rates as well as fees. Good luck.\"", "title": "" }, { "docid": "302691", "text": "This are my opinions on the subject: -People are tired of the corrupt system of bankers who poorly manage money, Bitcoin is built on trust, and more people are starting to trust it. Can you trust a banker? NO. Can you trust computer systems built on strict code that will always do what you tell them too? YES. To understand why Bitcoin is safe, one must first understand the block-chain technology. MORE INFO -More companies are starting to accept Bitcoin as payment, which creates more trust in the system, which brings more people interest. LIST OF COMPANIES -Bitcoin is a worldwide coin, you can pay your friend in Japan with Bitcoin and the transaction is done in 10 minutes, as opposed to 5-7 business day if done through a bank. The banker fee is huge, the Bitcoin miner fee is minimal. -Bitcoin is like Gold but better, Bitcoin is not built for everyday transactions just like gold, its not built for buying coffee either, its built to retain value which is why there is a finite amount (21 million). -A huge benefit of bitcoin is anyone with a smartphone or a computer can download an App and start accepting Bitcoins as payments. Gold is not easily trade-able. Bitcoins is as simple as sending a picture message. (NOTE: More than 2 billion smartphone users around the world around 3.7 billion internet users around the world all capable of one day trading using bitcoin) LIVE INTERNET USERS -Keep in mind, there is more than one crypto currency, all built on different ideas and systems, all performing with incredible gains. MORE INFO", "title": "" }, { "docid": "283635", "text": "By not saving some of your income you put yourself at risk of the following: If you are comfortable taking on those risks, then continue what you are doing (I'm not being sarcastic here...some people are perfectly comfortable taking on these risks). I plan on working until I die so I am not as concerned with saving for retirement but I do save some money for temporary job loss situations. Saving money presents its own set of issues (e.g. Where should I put the money?, Should I invest the money?, What type of investments?). If you have no interest in researching answers to these type of questions then I would suggest what others have already suggested: have part of your paycheck automatically siphoned into an account that can only be accessed by a trusted family member.", "title": "" }, { "docid": "324337", "text": "Potentially they could setup a trust for themselves and their heirs, donate the land to the trust. It might be able to go into the trust using the current 'on the books' value of the land (what the county/state are basing taxes on), then the trust can negotiate with the natural gas folks for the mineral rights An idea to bounce off your expert anyway.", "title": "" }, { "docid": "136460", "text": "\"I know some CEOs (for both big and small companies). A few have admitted to me on a few occasions they themselves don't have the slightest idea about being a CEO. The world changes too fast so they have absolutely no idea what's going to work and what isn't when it comes time to make decisions. All they can do is rely on the recommendations of the people that work under them at which point it becomes a matter of trust: Do you trust the recommendations from your CTO? Who did he trust to make that recommendation? The trust chain goes waaay down and it makes you wonder if the people who \"\"know\"\" (at the end of the chain) shouldn't have been able to just make the decision themselves.\"", "title": "" }, { "docid": "84119", "text": "Probably the easiest way to invest in hotel rooms in the U.S. is to invest in a Real Estate Investment Trust, or REIT. REITs are securities that invest in real estate and trade like a stock. There are different REITs that invest in different things: some own office buildings, some residential rentals, some hold mortgages, and some are diversified in lots of different types of real estate. There are also REITs that are exclusively invested in hotels. REITs are required to pay out at least 90% of their profits as dividends, and there are tax advantages to investing in REITs. You can search for a REIT on REIT.com's Searchable Directory. You can select a type (Lodging/Resorts), a stock exchange (NYSE), investment sector (equity), and a listing status (public), and you'll see lots of investments for you to consider.", "title": "" }, { "docid": "392852", "text": "\"A TFSA is a tax free savings account. It is a type of account where you can buy various investments like stocks, bonds, or funds (mutual, exchange traded, and money market). There are some other options but it's best to see what your bank or broker will allow. You probably specified the type of investment when you opened the account. You can look at your statements or maybe online to see what you're invested in. My guess is some kind of HISA (high interest savings account). This is kind of the default option for banks. The government created these accounts for a variety of reasons. The main stated reason was to encourage people to save. Obviously they also do things to get votes. There was an outcry after the change to a type of investment called \"\"investment trusts\"\". This could be seen as a consolation prize. These can be valuable to seniors for many reasons and they tend to vote more often. There was also an election promise to eliminate capital gains taxes in some fashion. It's not profitable for the government, in fact it supposedly cost the federal government $410 million in 2013. Banks make money by investing your deposit or by charging fees. You can see what every tax break 'costs' the government in lost revenue here http://www.fin.gc.ca/taxexp-depfisc/2013/taxexp1301-eng.asp#toc7\"", "title": "" }, { "docid": "442306", "text": "I'm not talking about the CFA, I'm talking about the entire finance industry, ethics make it all possible. Ethics provides room for trust between entities inside and outside the industry. Think about it, if you are a small cap private company wanting to go public, you trust that the underwriter will pay equity holders fairly for their units of equity. If there is no trust in the price, then there will be no underwriting, and no IPO for a new stock to enter the public markets. If there is no trust between fund managers and financial reports, the. There is no trust in estimated prospects and everything will be shriveled into speculative dangerous zones of future uncertainty. There's always a difference between being genuinely wrong and being a liar. TL;DR industry wide standards of ethics builds a foundation for trust which everyone uses directly or indirectly in finance.", "title": "" }, { "docid": "301987", "text": "\"There's enough places that directly accept BitCoin today that, call it whatever you want, it looks, walks, and quacks like a duck. And for transfers between two people that use different native currencies, it works a hell of a lot better and cheaper than most existing solutions. As for \"\"growing faster\"\", in eight years Bitcoin has gone from nonexistent to the 266th biggest \"\"company\"\" (in terms of market cap) in the world. Though still technically smaller than them, it makes the likes of Microsoft, Apple, and Google all look like sloths by comparison. To address \"\"trust\"\" - You're conflating \"\"trust of the issuer\"\" with \"\"trust of the bag-man\"\". With USD, you need to trust the good faith of the US Treasury; while that is certainly a pretty good bet, with Bitcoin, you don't need to trust anyone, because there is no issuing authority (no, not even the core devs could magically create more bitcoins out of thin air). That's different than, for example, trusting an online wallet or exchange with it, because then you have a third party holding your assets that can vanish to the Caymans overnight... But that wouldn't be any less true if you trusted USD to a random guy online. All that said, I'm still not invested in it because, although I love me some high return high volatility, I don't like the high risk of governments making my assets illegal overnight (China and Russia have already done so, though for now it seems more a statement of official policy than a real crime they go after people for). But as a medium of exchange - You bet I keep a small amount in my offline wallet for convenience!\"", "title": "" }, { "docid": "381384", "text": "He literally wrote a 1500 handbook on trusts and was a trust counsel at a huge bank for a long time so I definitely don't doubt his words. In one month I've learned what feels like an absolutely insane and mind blowing amount. I'll ask him after next class though to clarify what he meant. But he was also for sure talking about commercial purposes like mutual funds and stuff too. Edit: Im only posting here because a lot of stuff he says goes over my head as I am still a student and learning about trusts lol", "title": "" }, { "docid": "11601", "text": "To invest relatively small amounts in the real estate market, you could buy shares in a Real Estate Investment Trust (REIT), a type of mutual fund. Admittedly that's a very different proposition from trying to become a landlord; lower risk but lower return.", "title": "" }, { "docid": "453455", "text": "In the US the best way to solve the problem, IMHO, would be via a trust. Talk to a properly licensed trust/estate attorney and a tax adviser (EA/CPA licensed in your State). Using intermediary who's not a 501(c) organization may pose income tax issues to that intermediary as providing support to the needy is not a valid business expense. It may also pose gift tax issues, since the aggregate amounts may exceed the statutory exemption limits. Using a (non-revokable) trust you can avoid these issues, but others may come up (such as what to do with the trust income or undistributed moneys). Talk to the advisers about how to avoid them.", "title": "" }, { "docid": "432828", "text": "\"This would inevitably lead to a few gatekeepers from which everyone trusts the bonds (ibm GE etc), and millions of small businesses which will have absolutely no access to capital. Once this happens, you will quickly end up with a shadow banking system, where companies like GE switch from making stuff to basically being banks, giving loans to other small businesses with no access to capital, etc. This is basically done in China in a slightly different way, but, the core state-owned enterprises have near unlimited access to capital, and they use this advantage to invest in, and buy up, any and all interesting companies, simply because they're the only organizations that can essentially \"\"print\"\" money. (Whether you agree with it being printing money or not, the fact is GE / IBM would be able to issue bonds almost whenever they want, similar to the Treasury's monthly bond auctions, and other firms simply unable to.) So... then you have a few key companies with nearly unlimited right to \"\"print\"\" (used loosely) cash. They use this advantage to push on other businesses, buy them up, or control them in many ways. And then they use this position to eventually take over anything that looks interesting. What you're imagining as being an open market where everyone's bonds have full information will quickly devolve into information overload, and people choosing the well known brands as their trusted source. Once that happens, the whole idea falls apart, and those few firms will find a way to control not only the money supply, but also who gets to use their money. You will also have situations where some mom-and-pop takes John-LLC bonds as payment for dinner, and when they try to give John-LLC bonds to their suppliers, their suppliers say 'no thanks, we only deal in IBM bonds.\"\" Mom-and-pop will find themselves stuck with paper that nobody wants to accept. And mom-and-pop will quickly find themselves in a cash flow crisis, as they have tons of paper, but none of their suppliers will accept that paper. The only way to get out of this situation would be to convince IBM or GE to give Mom-and-pop some GE bonds in exchange for the John-LLC they have that nobody will accept. Of course, GE and IBM being in the enviable position as some of the few trusted money printers can refuse to accept John-LLC bonds except at a severe discount. \"\"We know John gave you John-LLC bonds to pay for his dinner worth $100, but, we'll only give you $40 worth of GE bonds for it.\"\" Mom-and-pop will quickly be fucked and go out of business due to having no \"\"hard currency\"\" (aka trusted currency) that they can use to purchase their raw materials. Demand for GE bonds will skyrocket as everyone seeks a safe-haven (a trusted currency almost everyone will accept), adn GE will find the entire market begging them to print bonds even at no interest just so that the money supply can increase to hold the full amount of trade occurring in the territory. This is then no different from the Fed during the recession a few years ago (and up until now) where they sell tons of bonds at rock-bottom interest rates simly because all the world is looking for a safe place to put their cash. The difference, of course, is that GE / IBM can take all this money and issue themselves HUGE bonuses, either on the cash directly or on the profit they've amassed by being the only trusted money issuer, whereas government officials can not.\"", "title": "" }, { "docid": "534294", "text": "> ...if we can't trust people to know what they want... I'm not saying people don't know what they want. I am saying what people want is easy to influence and every large, successful company does so. > When you say that not being able to resist buying skittles is a serious problem, while there are still people living on the streets, I think you need some perspective. I think both problems have the same issues at their core -- what is best for corporate America is not always what is best for the greater good. > I'd wager that what you're seeing as you get older is the poverty trap... No, what I see is that people solve problems as best they can with the tools they have learned. People make bad choices because they have an incomplete and/or bad assortment of tools to use. For example, someone might be worse off in life because he/she never learned the value of good organization skills. Another example is one person in a couple being unable to trust his/her partner because everyone before was untrustworthy. > ...which is caused by barriers to expanding earnings... Just had to throw your primary assertion back in, didn't ya? /grin > I'd still like to know whether you believe you yourself need to be protected from these marketing practices... I do believe I need protection from company marketing practices. I also believe I need protection from their products, influences on the market, environmental impacts, and employee treatment. FYI, I don't believe impulse buying racks at stores should be illegal but I do think it is a great illustration of how a company caters to needs that are different than our true innate needs.", "title": "" }, { "docid": "522619", "text": "\"The Trustee has allowed me to act as his \"\"agent\"\", continuing to pay bills, and take care of much of the administrative affairs for my mother's estate since I did all of it for years before she passed away. I was not paid for any of this work. ... The expenses were more than $30K last year, and there is still a punch list to go this year. The trust should reimburse your expenses and deduct them on the trust tax return. Since the Trust owned the property in 2015, and I will receive ownership this month, can last year's expenses incurred for the Trust be deducted again future income for my property this year? Not exactly. The trust will file its own tax return and will report the income/loss attributed to the beneficiaries per the trust rules. What is attributed to you will flow to your Schedule E. From there you own it and if it is a passive activity where the loss is limited - you can carry it forward and offset with future gain. The trustee will have to deal with all the paperwork. Do 1099-misc forms need to be filed for the contractors who worked to get it ready for rental? It is my understanding that since 2010 (and before 2010) landlords who are not in real-estate trade or business are not required to send out 1099. But it won't hurt if you do, also. In any case - for all of these issues you should talk to a tax adviser (EA/CPA licensed in your State).\"", "title": "" }, { "docid": "114520", "text": "\"First, you don't state where you are and this is a rather global site. There are people from Canada, US, and many other countries here so \"\"mutual funds\"\" that mean one thing to you may be a bit different for someone in a foreign country for one point. Thanks for stating that point in a tag. Second, mutual funds are merely a type of investment vehicle, there is something to be said for what is in the fund which could be an investment company, trust or a few other possibilities. Within North America there are money market mutual funds, bond mutual funds, stock mutual funds, mutual funds of other mutual funds and funds that are a combination of any and all of the former choices. Thus, something like a money market mutual fund would be low risk but quite likely low return as well. Short-term bond funds would bring up the risk a tick though this depends on how you handle the volatility of the fund's NAV changing. There is also something to be said for open-end, ETF and closed-end funds that are a few types to consider as well. Third, taxes are something not even mentioned here which could impact which kinds of funds make sense as some funds may invest in instruments with favorable tax-treatment. Aside from funds, I'd look at CDs and Treasuries would be my suggestion. With a rather short time frame, stocks could be quite dangerous to my mind. I'd only suggest stocks if you are investing for at least 5 years. In 2 years there is a lot that can happen with stocks where if you look at history there was a record of stocks going down about 1 in every 4 years on average. Something to consider is what kind of downside would you accept here? Are you OK if what you save gets cut in half? This is what can happen with some growth funds in the short-term which is what a 2 year time horizon looks like. If you do with a stock mutual fund, it would be a gamble to my mind. Don't forget that if the fund goes down 10% and then comes up 10%, you're still down 1% since the down will take more.\"", "title": "" }, { "docid": "119945", "text": ">Yes, but at the root of it is the consumer. Complaining that these trusted sources are not adhering to principles of journalistic integrity while they are desperately trying to survive, thrive and adapt to a completely shifting paradigm where competition is lowering the bar and the same consumers are unwilling to step up and reward journalistic integrity - this is what happens. Essentially we get what we pay for. Absolutely, but the difference is that western media now resembles grocery store gossip magazines more than journalism. > >We can lay blame on the media organizations as much as we care to, but the reality is we’ve reached a point where most people like to be given talking points and sound bites that vindicate their point of view rather than actually try to obtain facts and form their own opinions. The truth is rarely accessibly in the bite-size pieces our society today craves. That's well and good but they're trading on the credibility of yesteryear and selling us clickbait. Many people still trust these outlets but more are rejecting them. Social media accelerates agenda and de-emphasizes truth. > >Trust in the media is at an all time low for no other reason than we allowed it to happen and rewarded the media for going down that path. We’ve created a system that does not reward what we say we want from media, rather rewards the actions that show we want the complete opposite. We are customers. We didn't allow it to happen so much as companies evolved in that direction. The government also repealed fairness and anti propaganda legislation so that has contributed as well. > >If I may inquire, how many people reading this pay any premium for good journalism? I will be the first to sadly admit I do not. How many people take media outlets with disabled comments and archival seriously? > >Obviously this means I am also part of the problem despite making an effort to look at news from all sides - I am just a guilty as most to reinforcing the same system that has destroyed journalistic integrity. You're more moderate than most, at least you're questioning and examining your perspective, your reasons for belief and a willingness to change.", "title": "" }, { "docid": "420746", "text": "\"If there's indeed no reason to trust GS, i.e. those are just guides then the question is: Why do investors seem to care? Because there's a reason to trust. You're just reading the bottom line - the target price range. More involved investors read the whole report, including the description of the current situation, the premises for the analysis, the expectations on the firm's performance and what these expectations are based on, the analysis of how the various scenarios might affect the valuation, and the evaluation of chances of these scenarios to occur. You don't have to trust everything and expect it to be 100% correct, analysts are not prophets. But you do have an option of reading their reports and critically analyzing their conclusions. What you suspect GS of doing (\"\"I tend to believe those guys just want themselves a cheap buy price a few days before Q2 earnings release\"\") is a criminal offence.\"", "title": "" } ]
5a8afc3f55429971feec45c6	Who distributed the show from which the song "Friends" was sampled	[ { "docid": "10920908", "text": "Taina is an American sitcom that aired on Nickelodeon and distributed by Nelvana Limited. It was one of the last live-action comedy shows taped at Nickelodeon Studios but later moved to the Nickelodeon on Sunset in Hollywood, for its second season. The show aired from January 14, 2001 to May 11, 2002.", "title": "" }, { "docid": "39011161", "text": "\"Friends\" is a song by the American hip-hop group Whodini. The song reached #4 on the U.S. \"Billboard\" Hot R&B/Hip-Hop Songs chart. The song was less successful on the Hot 100, spending 3 weeks on the chart and peaking at #87. The Song was sampled on the Nickelodeon sitcom \"Taina\" on the song \"Thought that we were friends\", which was sung by Christina Vidal who played the title character.", "title": "" } ]	[ { "docid": "1553018", "text": "\"Lonely Swedish (The Bum Bum Song)\" is a novelty song by Canadian comedian Tom Green, created in 1999 for \"The Tom Green Show\". When the show moved to MTV, Green released it as a single, encouraging visitors to download the song (an mp3) for free from his website, burn it onto CDs and distribute it to friends. The music video was filmed in Seattle, Washington, home of the Swedish Medical Center, from which the name of the song is derived.", "title": "" }, { "docid": "51244715", "text": "\"Do You Mind\" is a single by American musician DJ Khaled. It was released on July 28, 2016 by We the Best Music Group and Epic Records as the fourth single of DJ Khaled's ninth studio album, \"Major Key\". The song features guest appearances from Nicki Minaj, Chris Brown, Jeremih, Future, August Alsina and Rick Ross. The song samples \"Lovers and Friends\" performed by Lil Jon & the East Side Boyz, featuring Usher and Ludacris, which also samples \"Lovers and Friends\" performed by Michael Sterling from his 1990 album \"Trouble\" and also samples \"Money Ain't a Thang\" performed by Jermaine Dupri, featuring Jay Z in Future's verse. The song was certified Platinum by the Recording Industry Association of America (RIAA).", "title": "" }, { "docid": "56107", "text": "In statistics and in statistical physics, the Metropolis–Hastings algorithm is a Markov chain Monte Carlo (MCMC) method for obtaining a sequence of random samples from a probability distribution for which direct sampling is difficult. This sequence can be used to approximate the distribution (e.g., to generate a histogram), or to compute an integral (such as an expected value). Metropolis–Hastings and other MCMC algorithms are generally used for sampling from multi-dimensional distributions, especially when the number of dimensions is high. For single-dimensional distributions, other methods are usually available (e.g. adaptive rejection sampling) that can directly return independent samples from the distribution, and are free from the problem of autocorrelated samples that is inherent in MCMC methods.", "title": "" }, { "docid": "32490739", "text": "\"Otis\" is a song by American hip hop artists Kanye West and Jay-Z, from their first collaborative album \"Watch the Throne\" (2011). The song posthumously features soul singer Otis Redding, whose version of \"Try a Little Tenderness\" is sampled in the song. The production was covered solely by West. The track was premiered by Funkmaster Flex's Hot 97 radio show and was released onto the Internet the day afterward. Lyrically, the song has the two rappers sharing lines discussing wealth, decadence and fame. The track received highly positive reviews from music critics who praised the trading off of verses by the two rappers and the Redding-sampled beat, which was compared to the style heard on West's \"The College Dropout\". Several publications placed the song amongst the best of the year.", "title": "" }, { "docid": "140841", "text": "In statistics, a statistic is \"sufficient\" with respect to a statistical model and its associated unknown parameter if \"no other statistic that can be calculated from the same sample provides any additional information as to the value of the parameter\". In particular, a statistic is sufficient for a family of probability distributions if the sample from which it is calculated gives no additional information than does the statistic, as to which of those probability distributions is that of the population from which the sample was taken.", "title": "" }, { "docid": "4478910", "text": "Amigo and Friends (also known in Spanish as Cantinflas y Sus Amigos) is an educational children's cartoon that was based on the Mexican cartoon series \"Cantinflas Show\" in 1979. The show, which concentrates on a wide range of subjects intended to educate children, follows Amigo, a little comical character from Mexico, who goes on educational adventures through time and space and gets to visit Shakespeare, see the ancient pyramids, and even travels to other planets. The animated Amigo is based on the legendary character, Cantinflas played by the Mexican actor and comedian Mario Moreno Reyes. The show was created and produced by Televisa, then known as Telesistema Mexicano. The company was also responsible for the distribution of the show in Mexico.", "title": "" }, { "docid": "11620697", "text": "The Oddventures of Mr. Cool is the seventh studio album of Filipino rap artist Francis Magalona, released in 1998. The album contains more of a mellow, urban-style kind of music which is reminiscent of his debut album \"Yo!\". Several songs on \"The Oddventures of Mr. Cool\" are sampled from foreign artists, including Whodini's \"Friends\", as heard on \"Friends\".", "title": "" }, { "docid": "867671", "text": "In statistics, importance sampling is a general technique for estimating properties of a particular distribution, while only having samples generated from a different distribution than the distribution of interest. It is related to umbrella sampling in computational physics. Depending on the application, the term may refer to the process of sampling from this alternative distribution, the process of inference, or both.", "title": "" }, { "docid": "49234838", "text": "All Your Friends' Friends is a hip hop compilation album released by K Records on November 11, 2014. It was produced by Thee Xntrx (Eprhyme and Smoke of Oldominion, who also appear on the album) and pairs verses from various Pacific Northwest rappers with samples from older K Records artists, including punk and indie rock bands. Rappers on the compilation include The Chicharones, MG! The Visionary, and members of Oldominion, while samples are taken from Mirah, The Microphones, and Jeremy Jay.", "title": "" }, { "docid": "509709", "text": "In statistics, Gibbs sampling or a Gibbs sampler is a Markov chain Monte Carlo (MCMC) algorithm for obtaining a sequence of observations which are approximated from a specified multivariate probability distribution, when direct sampling is difficult. This sequence can be used to approximate the joint distribution (e.g., to generate a histogram of the distribution); to approximate the marginal distribution of one of the variables, or some subset of the variables (for example, the unknown parameters or latent variables); or to compute an integral (such as the expected value of one of the variables). Typically, some of the variables correspond to observations whose values are known, and hence do not need to be sampled.", "title": "" }, { "docid": "11706433", "text": "\"Faithful\" is the fifth and final single from rapper Common's sixth album \"Be\". It is produced by Kanye West, who samples DJ Rogers' \"Faithful to the End\" for the song's beat. The sample was recreated by percussionist Ken Lewis. The song also features keyboard playing by James Poyser as well as guest vocals by John Legend and neo-soul singer Bilal. The song was not heavily promoted upon release and failed to chart. The song also samples Faith Evans song of the same name on her third album \"Faithfully\" which was released in 2001.", "title": "" }, { "docid": "2337794", "text": "\"My Name Is Mud\" is a song by the American rock band Primus and is the first single from the 1993 album \"Pork Soda\". The lyrics are written from the point of view of a blue-collar man, Aloysius Devandander Abercrombie, who has killed his friend after an argument and is now trying to bury him. The song samples the line \"Where are you goin' city boy?\" from the film \"Deliverance\".", "title": "" }, { "docid": "54294205", "text": "Alpha Team was a musical rave duo from Chicago who had a pop and dance hit with the song \"Speed\". This song sampled the theme from Speed Racer and also included snippets of dialog from that show. The song peaked at #74 on the Billboard Hot 100, staying on that chart for eight weeks beginning in January 1993.", "title": "" }, { "docid": "332213", "text": "A \"Z\"-test is any statistical test for which the distribution of the test statistic under the null hypothesis can be approximated by a normal distribution. Because of the central limit theorem, many test statistics are approximately normally distributed for large samples. For each significance level, the \"Z\"-test has a single critical value (for example, 1.96 for 5% two tailed) which makes it more convenient than the Student's \"t\"-test which has separate critical values for each sample size. Therefore, many statistical tests can be conveniently performed as approximate \"Z\"-tests if the sample size is large or the population variance is known. If the population variance is unknown (and therefore has to be estimated from the sample itself) and the sample size is not large (n < 30), the Student's \"t\"-test may be more appropriate.", "title": "" }, { "docid": "41559308", "text": "In statistics, some Monte Carlo methods require independent observations in a sample to be drawn from a one-dimensional distribution in sorted order. In other words, all \"n\" order statistics are needed from the \"n\" observations in a sample. The naive method performs a sort and takes \"O\"(\"n\" log \"n\") time. There are also \"O\"(\"n\") algorithms which are better suited for large \"n\". The special case of drawing \"n\" sorted observations from the uniform distribution on [0,1] is equivalent to drawing from the uniform distribution on an \"n\"-dimensional simplex; this task is a part of sequential importance resampling.", "title": "" }, { "docid": "962769", "text": "Star Song Communications is a Christian record label that was started in 1976 by Wayne Donowho, who recruited his friend Darrell Harris. It gained notoriety when it issued Resurrection Band's ground-breaking debut album, Awaiting Your Reply in 1978. Originally a distribution deal was made with Benson Records. From 1983 until 1986 distribution was done by Word Records. After that, a deal was made with Sparrow Records. Independent distribution was started in 1989 and picked up distribution for ForeFront records and DC Talk in 1991. This distribution was maintained until the sale of the company to EMI and the launch of Chordant Distribution in 1994.", "title": "" }, { "docid": "12653143", "text": "\"Rap Name\" is the debut single of American rapper Obie Trice, released as a limited edition vinyl recording, taken from the deluxe edition of the soundtrack to the film \"8 Mile\". The song features vocals from fellow-label mate Eminem, who sampled the track in two tracks for his album \"The Eminem Show\", released earlier in 2002. These tracks are \"Drips\" and the intro of the album's lead single, \"Without Me\", as well as a few other lines from the song. The song also features a vocal sample of The Notorious B.I.G. from his song \"Long Kiss Goodnight\" from the album \"Life After Death\". The official video was filmed in Detroit with featured cameo appearances by Eminem's group D12.", "title": "" }, { "docid": "3397642", "text": "\"So Easy\" is a song by Norwegian duo Röyksopp, released as their first single. It was first made available in 1999, with only 500 copies made and distributed. It was later re-released on Röyksopp's debut album \"Melody A.M.\" \"So Easy\" contains instrumental and vocal samples from a 1960s cover version of the Burt Bacharach/Hal David song \"Blue on Blue\" (often misheard as \"Who are you\") recorded by a Swedish vocal group called Gals & Pals. The sampled lyrics are \"Blue on blue, heartache on heartache/Blue on blue, Now that we are through.\"", "title": "" }, { "docid": "1829858", "text": "\"Hit 'Em Up\" is a diss song by rap artist 2Pac featuring his group the Outlawz. It is the B-side to the single \"How Do U Want It\", released on June 4, 1996. The song’s lyrics contain vicious insults to several East Coast rappers, chief among them, Shakur's former friend turned rival, The Notorious B.I.G., also known as Biggie Smalls. The song was recorded in Los Angeles, California at Can Am Studios in May 1996. Reporter Chuck Philips, who interviewed Shakur at Can Am, described the song as \"a caustic anti-East Coast crusade in which the rapper threatens to eliminate Biggie, Sean Combs (Puffy), and a slew of Bad Boy artists and other New York acts.\" The song was produced by long-time collaborator Johnny \"J\" and samples the bassline from \"Don't Look Any Further\" by Dennis Edwards and interpolates \"Get Money\" by Biggie Smalls group Junior M.A.F.I.A., which used the Dennis Edwards sample as well. The song's chorus contains an interpolation of Yellowman's 1982 hit reggae single 'Zungguzungguguzungguzeng'. The video, itself described as infamous, includes impersonations of Biggie, Puffy and Lil' Kim.", "title": "" }, { "docid": "7093060", "text": "The ziggurat algorithm is an algorithm for pseudo-random number sampling. Belonging to the class of rejection sampling algorithms, it relies on an underlying source of uniformly-distributed random numbers, typically from a pseudo-random number generator, as well as precomputed tables. The algorithm is used to generate values from a monotone decreasing probability distribution. It can also be applied to symmetric unimodal distributions, such as the normal distribution, by choosing a value from one half of the distribution and then randomly choosing which half the value is considered to have been drawn from. It was developed by George Marsaglia and others in the 1960s.", "title": "" }, { "docid": "520670", "text": "In statistics, a sampling distribution or finite-sample distribution is the probability distribution of a given statistic based on a random sample. Sampling distributions are important in statistics because they provide a major simplification en route to statistical inference. More specifically, they allow analytical considerations to be based on the sampling distribution of a statistic, rather than on the joint probability distribution of all the individual sample values.", "title": "" }, { "docid": "34307690", "text": "\"If I Had No Loot\" is a song by American R&B group Tony! Toni! Toné!. It was released on June 1, 1993, as the lead single from their 1993 album \"Sons of Soul\". The song was produced by Tony! Toni! Toné! and co-written by group member Raphael Wiggins, who said that it is about fair-weather friends. It has a new jack swing beat, pronounced guitar licks, and vocal samples from Boogie Down Productions' 1987 song \"Remix for P Is Free\" and Ice Cube's 1991 song \"The Wrong Nigga to Fuck Wit\".", "title": "" }, { "docid": "35331883", "text": "In statistics, the matrix \"t\"-distribution (or matrix variate \"t\"-distribution) is the generalization of the multivariate \"t\"-distribution from vectors to matrices. The matrix \"t\"-distribution shares the same relationship with the multivariate \"t\"-distribution that the matrix normal distribution shares with the multivariate normal distribution. For example, the matrix \"t\"-distribution is the compound distribution that results from sampling from a matrix normal distribution having sampled the covariance matrix of the matrix normal from an inverse Wishart distribution.", "title": "" }, { "docid": "8140616", "text": "In the theory of probability and statistics, the Dvoretzky–Kiefer–Wolfowitz inequality predicts how close an empirically determined distribution function will be to the distribution function from which the empirical samples are drawn. It is named after Aryeh Dvoretzky, Jack Kiefer, and Jacob Wolfowitz, who in 1956 proved", "title": "" }, { "docid": "1179250", "text": "Garfield Goose and Friends is a children's television show produced by WGN-TV in Chicago, Illinois, United States from 1955 to 1976. The show was known as \"Garfield Goose and Friend\" from 1952 to 1955 when it aired on WBKB and WBBM-TV. It was the longest running puppet show on television. The host of the show was Frazier Thomas, who did all of the talking. The show centered on a clacking goose puppet named Garfield Goose, who considered himself \"King of the United States.\" There were many other puppet characters such as Romberg Rabbit, Macintosh Mouse, Chris Goose (Garfield's nephew who was born on Christmas, hence \"Christmas Goose\") and a sleepy bloodhound called Beauregard Burnside III (whose name happened to be a mix of two American Civil War generals). The show used a \"Little Theater Screen\", upon which the camera would zoom before cartoons such as \"Clutch Cargo\" and \"Space Angel\" were broadcast.", "title": "" }, { "docid": "3197569", "text": "\"Talk About Our Love\" is a song by American recording artist Brandy Norwood, taken from her fourth studio album, \"Afrodisiac\" (2004). It was written by Kanye West, who also appears as a featured artist on it, and Harold Lilly, while production was handled by the former. Due to the song's use of a sample of Mandrill's 1978 song \"Gilly Hines\", penned by band members Claude Cave II, and Carlos, Louis and Ricardo Wilson, they are also credited as writers. Lyrically, \"Talk About Our Love\" is about a relationship that lacks support by family and friends; the music consists of an arrangement using a bass, keyboards, drums, and string instruments, the latter of which were provided by Israeli violinist Miri Ben-Ari.", "title": "" }, { "docid": "35582238", "text": "Closer is the third single from Capone-N-Noreaga's debut album \"The War Report\". The song samples \"Closer Than Friends\" by Surface and \"Promise Me\" by Luther Vandross. All of the verses in the song are performed by Noreaga whilst singer Nneka performs the hook.", "title": "" }, { "docid": "25071233", "text": "\"Somebody Loves You Baby (You Know Who It Is)\" is one of Patti LaBelle's signature songs released as a single in 1991 on the MCA Records label. The song was the second single to be released from LaBelle's acclaimed gold-selling CD, \"Burnin'\". The song was co-written by LaBelle's friend and former Philadelphia International artist Bunny Sigler, who also produced the song. The song reached number two on the Hot R&B Singles chart in early 1992. Like her previous single, \"Somebody Loves You...\" was also shot at the Apollo. Rapper Plies later sampled the song for his track, \"Somebody (Loves You)\" off his second release, \"Definition of Real\".", "title": "" }, { "docid": "15437538", "text": "\"Represent\" is the ninth song on Nas' debut album \"Illmatic\". It is produced by DJ Premier who samples Lee Irwin's \"Thief of Baghdad\" for the song's beat. The song's minimalistic beat consists of an electric piano sample and bells. Nas raps three verses and performs a spoken dedication to his friends at the track's end, but does not contribute to the chorus. Nas' verses deal with his life in the streets and his criminal ties. One specific lyric was \"pulling the Tec out the dresser\" was criticized by Jay-Z on his diss song \"Takeover.\" Nas dedicates the song to a long list of people including future hip hop artists Cormega and Lakey the Kid. RapReviews.com describes \"Represent\" as a \"certified banger.\"", "title": "" }, { "docid": "23864280", "text": "Parity learning is a problem in machine learning. An algorithm that solves this problem must guess the function \"ƒ\", given some samples (\"x\", \"ƒ\"(\"x\")) and the assurance that \"ƒ\" computes the parity of bits at some fixed locations. The samples are generated using some distribution over the input. The problem is easy to solve using Gaussian elimination provided that a sufficient number of samples (from a distribution which is not too skewed) are provided to the algorithm.", "title": "" } ]
28	Tax whilst starting a business in full time employment	[ { "docid": "250640", "text": "With a limited company, you'll have to pay yourself a salary through PAYE. With income from your other job taking you over the higher-rate threshold, you should inform HMRC of this and get a tax code of DO for the second job, meaning 40% tax (and also both employer's and employee's National Insurance) will be deducted from the whole amount of the salary. See here. Dividends should be like any other dividend -- you won't pay extra tax when you receive them, but will have to declare them on your tax return and pay the tax later. See the official information here. You'll get a £5,000 tax allowance for dividends, but they'll still count as income for purposes of hitting the higher-rate threshold. I think in practice this means the first £5,000 will be tax-free, and the rest will be taxed at 32.5%. But note that you have to pay yourself at least the minimum wage as salary, not as dividend. I can't see IR35 being an issue. However, I'm not a professional, and this situation is complicated enough to need professional advice. Talk to an accountant or a tax advisor.", "title": "" } ]	[ { "docid": "385320", "text": "I do NOT know the full answer but I know here are some important factors that you need to consider : Do you have a physical location in the United States? Are you working directly from Canada? With a office/business location in the United States your tax obligation to the US is much higher. Most likely you will owe some to the state in which your business is located in Payroll Tax : your employer will likely want to look into Payroll tax, because in most states the payroll tax threshold is very low, they will need to file payroll tax on their full-time, part-time employees, as well as contractor soon as the total amount in a fiscal year exceeds the threshold Related to No.1 do you have a social security number and are you legally entitled to working in the States as an individual. You will be receiving the appropriate forms and tax withholding info Related to No.3 if you don't have that already, you may want to look into how to obtain permissions to conduct business within the United States. Technically, you are a one person consulting service provider. You may need to register with a particular state to obtain the permit. The agency will also be able to provide you with ample tax documentations. Chances are you will really need to piece together multiple information from various sources to resolve this one as the situation is specific. To start, look into consulting service / contractor work permit and tax info for the state your client is located in. Work from state level up to kick start your research then research federal level, which can be more complex as it is technically international business service for Canada-US", "title": "" }, { "docid": "130118", "text": "I'm afraid you're mistaking 401k as an investment vehicle. It's not. It is a vehicle for retirement. Roth 401k/IRA has the benefit of tax free distributions at retirement, and as long as you're in the low tax bracket - it is for your benefit to take advantage of that. However, that is not the money you would be using to start a business or buy a home (except for maybe up to $10K you can withdraw without penalty for first time home buyers, but I wouldn't bother with $10k, if that's what will help you buying a house - maybe you shouldn't be buying at all). In addition, you should make sure you take advantage of the employer 401k match in full. That is free money added to your Traditional 401k retirement savings (taxed at distribution). Once you took the full advantage of the employer's match, and contributed as much as you consider necessary for your retirement above that (there are various retirement calculators on line that can help you in making that determination), everything else will probably go to taxable (regular) savings/investments.", "title": "" }, { "docid": "223170", "text": "Since your YouTube income is considered self-employment income and because you probably already made more than $400 in net income (after deducting expenses from the $4000 you've received so far), you will have to pay self-employment tax and file a return. This is according to the IRS's Publication 17 (2016), Your Federal Income Tax, so assumes the same rules for 2016 will remain in effect for 2017: You are self-employed if you: Carry on a trade or business as a sole proprietor, Are an independent contractor, Are a member of a partnership, or Are in business for yourself in any other way. Self-employment can include work in addition to your regular full-time business activities, such as certain part-time work you do at home or in addition to your regular job. You must file a return if your gross income is at least as much as the filing requirement amount for your filing status and age (shown in Table 1-1). Also, you must file Form 1040 and Schedule SE (Form 1040), Self-Employment Tax, if: Your net earnings from self-employment (excluding church employee income) were $400 or more, or You had church employee income of $108.28 or more. (See Table 1-3.) Use Schedule SE (Form 1040) to figure your self-employment tax. Self-employment tax is comparable to the social security and Medicare tax withheld from an employee's wages. For more information about this tax, see Pub. 334, Tax Guide for Small Business. I'd also note that your predicted income is getting close to the level where you would need to pay Estimated Taxes, which for self-employed people work like the withholding taxes employers remove their employees paychecks and pay to the government. If you end up owing more than $1000 when you file your return you could be assessed penalties for not paying the Estimated Taxes. There is a grace period if you had to pay no taxes in the previous year (2016 in this case), that could let you escape those penalties.", "title": "" }, { "docid": "250766", "text": "The benefits and taxes thing, in my opinion is the biggie. Most people don't realize that the cost to the company for a full-time employee with benefits can be 2x or even 3x the amount they see in their paycheck. Health plans are extremely expensive. Even if you are having money taken from your check for health insurance, it is often just a fraction of the total cost, and the employer is subsidizing the rest. More expensive benefits that contractors don't typically get are 401K matches and paid vacation days. When contractors call in sick or don't work because it is a national holiday, they don't get paid for that day. Also, see that line on your paycheck deducting for Social security and Medicare? That is only half of the tax. The employer pays an equal amount that is not shown on that statement. Also, they pay taxes that go towards unemployment benefits , and may be required to pay higher taxes if they churn through a lot of full-time employees. You can usually let contractors go with relative impunity . For the unemployment tax reasons, not paying for people's days off or benefits, a lot less paperwork, and less risk to the business associated with committing to full-time employees all provide value to the company. Thus companies are willing to pay more because they are getting more. Think of it like a cell phone-contract. If you commit to a three year contract it can be a pain/expensive to get out of the deal early, but you will probably get a better rate in exchange for the risk being shifted to your end of the deal.", "title": "" }, { "docid": "541809", "text": "\"No, your business cannot deduct your non-business expenses. You can only deduct from your business income those reasonable expenses you paid in order to earn income for the business. Moreover, for there to be a tax benefit, your business generally has to have income (but I expect there are exceptions; HST input tax credits come to mind.) The employment income from your full-time job wouldn't count as business income for your corporation. The corporation has nothing to do with that income – it's earned personally, by you. With respect to restaurant bills: These fall under a category known as \"\"meals & entertainment\"\". Even if the expense can be considered reasonable and business-related (e.g. meeting customers or vendors) the Canada Revenue Agency decided that a business can only deduct half of those kinds of expenses for tax purposes. With respect to gasoline bills: You would need to keep a mileage and expense log. Only the portion of your automobile expenses that relate to the business can be deducted. Driving to and from your full-time job doesn't count. Of course, I'm not a tax professional. If you're going to have a corporation or side-business, you ought to consult with a tax professional. (A point on terminology: A business doesn't write off eligible business expenses — it deducts them from business income. Write off is an accounting term meaning to reduce the value of an asset to zero. e.g. If you damaged your car beyond repair, one could say \"\"the car is a write-off.\"\")\"", "title": "" }, { "docid": "139501", "text": "\"There are a few sites out there that can give you some reasoning behind the request. LegalZoom, for instance. To quote the LZ doc in case the link dies: Employee vs. Independent Contractor If a worker is an employee, the employer is responsible for paying Social Security, unemployment insurance, Medicare, and possibly other costs like workers' compensation insurance for the employee; at the end of the tax year, the employer is responsible for compiling all necessary payroll reports, including W-2 forms. If a worker is an independent contractor, the employer is not responsible for any of the above taxes or payments, and the only added paperwork is the issuing of a 1099 to the independent contractor at the end of the tax year, if he or she has made more than $600 with the employer. As Kent suggested, you should speak with an attorney (really you need one if setting up an LLC). There are a lot of companies out there these days that try to classify people as contractors rather than full-time employees as it gets them out of paying benefits and dealing with taxes. This is being heavily cracked down on, and several \"\"contractor\"\" employees are winning lawsuits to get full-time status. If you are truly acting as a contractor, then setting up an LLC can help with a few items such as taxes and protection on certain business aspects (see comments below regarding this). It's easy and relatively cheap (cost me about $250 with extra legal advice tacked on). If you are reporting directly to a manager with the company, or really working in any way that isn't consistent with the definition of a contractor, then I'd turn down the offer and ask to be made a FT employee. Additional information: https://www.sba.gov/content/hire-contractor-or-employee\"", "title": "" }, { "docid": "200263", "text": "Debt collectors are just doing their job as many people want to evade payment by not responding and skipping their debts, and they talk tough to force people found to make their obligated payments based on what they can afford and that’s all. I’m in the UK, but I assume the process is similar. Before I begin, I worked in debt collection and I presume that the debt collection agency have requested details for a source like a college and you have been returned as a possible match as you name is identical to their debtor but with differing date of birth etc. College/University students are very nomadic in nature and addresses aren’t very helpful when they are not current, but details of a current address/employer to a very similar name would be a possible lead to debtor and the debt collector is simply acting on flawed information which is fairly rare, and cases such as these are resolved when you can simply confirm your date of birth and other details so that they can eliminate you from their chasing activities. Whilst you may feel uncomfortable about giving your details, you are not the debtor and will have to confirm this, the debt collector is only interested in collection of valid debts values, and the current letter is most likely a standard letter to get you to act assuming that you are the debtor. If you try to ignore this or only partly answer their contact by telling them not to contact your employer etc, they will assume that you are the debtor and step up pursuit by contacting at work by phone, in person, or by other means, and you employer will see you in a bad light… I would advise you to write to them a one-time only letter confirming details of your home address and insist on correspondence in writing only to that home address, in addition you should confirm your full name including full middle names, date of birth, that you have never attended the college in question, agreed to any such debt in writing, and that you are not the correct data subject as the ss number also differs. The letter should also go on to state a range of costs which require payment before you act further, ie subsequent letter $xx.xx amount attending court $xx.xx per hour(not cheap) and that if they harass you or otherwise affect your standing with your credit reference, or employer or anyone else that you ‘Will’ take further action and ‘May’ take them to your ‘Local’ court and pursue the costs list above and losses as a result of their actions including pain and suffering. Speak tough and mean business and act decisively and your message will win through, share your details with them once and above all copy your employer in so that they know this is a case of mistaken identity. You can add a large heading at the top of the letter of ‘Mistaken Identity’ to prove your point.", "title": "" }, { "docid": "216789", "text": "\"The standard is actually 30 hours a week over a given period of time (3-12 months of the previous taxable year). The interesting problem for the prototypical employer who wants to offer benefits to as few employees as possible is ERISA Sec. 510. According to the above poster, companies want to avoid hiring full time positions. However, based on employer needs, only hiring part time workers will not be feasible for many businesses. Furthermore, if employers restrict hours for the purpose of denying access to benefits, they may be violating ERISA Sec. 510, which would lead to a major lawsuit for that business. As ERISA is an opt-in class action statute, as well as a generous attorney fee statute (it's easier for plaintiff's lawyers to make the defense pay their legal fees, see ERISA 502(g), CIGNA v. Amara), it would be unwise for employers to simply refuse to hire any more full time employees. Of course, companies will be looking to avoid \"\"overpaying\"\" for benefits in any way they can. But simplistic conclusions, such as vexu gave, that they will not hire full time workers fails to grasp both the complexity of PPACA and the consequences of a given employer's actions.\"", "title": "" }, { "docid": "522798", "text": "There are 2 main types of brokers, full service and online (or discount). Basically the full service can provide you with advice in the form of recommendations on what to buy and sell and when, you call them up when you want to put an order in and the commissions are usually higher. Whilst an online broker usually doesn't provide advice (unless you ask for it at a specified fee), you place your orders online through the brokers website or trading platform and the commissions are usually much lower. The best thing to do when starting off is to go to your country's stock exchange, for example, The ASX in Sydney Australia, and they should have a list of available brokers. Some of the online brokers may have a practice or simulation account you can practice on, and they usually provide good educational material to help you get started. If you went with an online broker and wanted to buy Facebook on the secondary market (that is on the stock exchange after the IPO closes), you would log onto your brokers website or platform and go to the orders section. You would place a new order to buy say 100 Facebook shares at a certain price. You can use a market order, meaning the order will be immediately executed at the current market price and you will own the shares, or a limit price order where you select a price below the current market price and wait for the price to come down and hit your limit price before your order is executed and you get your shares. There are other types of orders available with different brokers which you will learn about when you log onto their website. You also need to be careful that you have the funds available to pay for the share at settlement, which is 3 business days after your order was executed. Some brokers may require you to have the funds deposited into an account which is linked to your trading account with them. To sell your shares you do the same thing, except this time you choose a sell order instead of a buy order. It becomes quite simple once you have done it a couple of times. The best thing is to do some research and get started. Good Luck.", "title": "" }, { "docid": "347723", "text": "\"I don't see why you would need an \"\"international tax specialist\"\". You need a tax specialist to give you a consultation and training on your situation, but it doesn't seem too complicated to me. You invoice your client and get paid - you're a 1099 contractor. They should issue you a 1099 at the end of the year on everything they paid you. Once you become full-time employee - you become a W2 employee and will get a W2 at the end of the year on the amounts paid as such. From your perspective there's nothing international here, regular business. You have to pay your own taxes on the 1099 income (including SE taxes), they have to withhold taxes from your W2 income (including FICA). Since they're foreign employers, they might not do that latter part, and you'll have to deal with that on your tax return, any decent EA/CPA will be able to accommodate you with that. For the employer there's an issue of international taxation. They might have to register as a foreign business in your state, they might be liable for some payroll taxes and State taxes, etc etc. They might not be aware of all that. They might also be liable (or exempt) for Federal taxes, depending on the treaty provisions. But that's their problem. Your only concern is whether they're going to issue you a proper W2 and do all the withholdings or not when the time comes.\"", "title": "" }, { "docid": "326329", "text": "In the US we have social security taxes, where for a full time employee the company pays half and the employee pays half. When you work as a business, what we call 1099 for the form that the wages are reported on, then the contractor pays the full amount of social security tax. There are times when a contractor can negotiate a higher rate because the company does not have to pay that tax. However, most of the time the company just prefers to negotiate the rate based on your value. If you are a 60K year guy, then that is what they will pay you. From the company's perspective it does not matter what your tax rate is, only the value you can bring to the company. If you can add about 180K to the bottom line, then they will be happy to pay you 60K, and you should be happy to get it. Here in the US a contractor can expect to make about 7.5% more of an equivalent employee because of the social security tax savings to the company. However, not all companies are willing to provide that in compensation. Some companies see the legal and administrative costs of employees as normal, and the same costs with contractors as extra so they don't perceive a cost savings. There are other things that would preclude employers from giving the bump although it is logical to do so. First you will really have to feel out your employer for the attitude on the subject. Then I would make a logical case if they are open to providing extra compensation in return for tax savings. If I am an employee at 60K, you would also have to pay the government 18K. How about you pay me 75K as a contractor instead? That would be a great deal for all in the US.", "title": "" }, { "docid": "350669", "text": "Certainly reading the recommended answers about initial investing is a great place to start and I highly recommend reading though that page for sure, but I also believe your situation is a little different than the one described as that person has already started their long-term career while you are still a couple years away. Now, tax-advantaged accounts like IRAs are amazingly good places to start building up retirement funds, but they also lock up the money and have a number of rules about withdrawals. You have fifteen thousand which is a great starting pot of money but college is likely to be done soon and there will likely be a number of expenses with the transition to full-time employment. Moving expenses, first month's rent, nursing exams, job search costs, maybe a car... all of this can be quite a lot especially if you are in a larger city. It sounds like your parents are very helpful though which is great. Make sure you have enough money for that transition and emergency expenses first and if there is a significant pool beyond that then start looking at investments. If you determine now is the best time to start than then above question is has great advice, but even if not it is still well worth taking some time to understand investing through that question, my favorite introduction book on the subject and maybe even a college course. So when you land that first solid nursing job and get situated you can start taking full advantage of the 401K and IRAs.", "title": "" }, { "docid": "592192", "text": "My advice is that if you've got the money now to pay off your student loans, do so. You've saved up all of that money in one year's time. If you pay it off now, you'll eliminate all of those monthly payments, you'll be done paying interest, and you should be able to save even more toward your business over the next year. Over the next year, you can get started on your business part time, while still working full time to pile up cash toward your business. Neither you nor your business will be paying interest on anything, and you'll start out in a very strong position. The interest on your student loans might be tax deductible, depending on your situation. However, this doesn't really matter a whole lot, in my opinion. You've got about $22k in debt, and the interest will cost you roughly $1k over the next year. Why pay $1k to the bank to gain maybe $250 in tax savings? Starting a business is stressful. There will be good times and bad. How long will it take you to pay off your debt at $250 a month? 5 or 6 years, probably. By eliminating the debt now, you'll be able to save up capital for your business even faster. And when you experience some slow times in your business, your monthly expenses will be less.", "title": "" }, { "docid": "56924", "text": "Your gut feeling is absolutely spot on - you shouldn't be worrying about pension now, not at the age of 25. Assuming that you're not a footballer in the middle of the most productive part of your career and already have a fat wad of crunchy banknotes under your pillow that you're looking to set aside for a rainy day when you won't be able to play at your prime any longer. That doesn't mean you shouldn't invest, nor that means that you mustn't save. There are several factors at play here. First of all as a young person you are likely to have a high tolerance for risk, there is still plenty of time to recover should expected returns not materialise. Even a pension fund with the most aggressive risk / return strategy might just not quite do it for you. You could invest into education instead, improve health, obtain a profitable skill, create social capital by building connections, pay for experience, buy a house, start a family or even a business. Next, as a young professional you're unlikely to have reached your full earning potential yet and due to the law of diminishing marginal utility a hundred pounds per month now have greater utility (i.e. positive impact on your lifestyle) than a seven hundred pounds will in 7-10 years time once your earnings plateaued. That is to say it's easier to save £700 month from £3000 and maintain a reasonable level of personal comfort than carve £100 from £1300 monthly income. And last, but not the least, lets face it from a human point of view - forty years is a very long investment horizon and many things might and will change. One of the downsides of UK pensions is that you have very little control over the money until you reach a certain age. Tactically I suggest saving up to build a cushion consisting of cash or near cash assets; the size of the stash should be such that it is enough to cover all of your expenses from a minimum of 2 months to a maximum of a year. The exact size will depend on your personal comfort level, whatever social net you have (parents, wife, partner) and how hard it will be to find a new source of income should the current cease to produce cash. On a strategic level you can start looking into investing any surplus cash into the foundation of what will bring joy and happiness into the next 40 years of your life. Your or your partners training and education is one of the most sensible choices whilst you're young. Starting a family is another one. Both might help you reach you full earning potential much quicker. Finding what you love to do and learning how to do it really well - cash can accelerate this process bringing you quicker there you want to be. If you were a start-up business in front of a huge uncaptured market would you rather use cash to pay dividends or finance growth?", "title": "" }, { "docid": "361482", "text": "Stock awards by employers are treated and taxed as salary. I.e.: you pay ordinary rate income tax, FICA taxes, State taxes etc. The fact that you got your salary in shares and not cash is irrelevant for tax purposes. Once you got the shares and paid your taxes on them, the treatment is the same as if you got the salary and immediately bought the shares. Holding period for capital gains tax purposes starts at the time you paid your taxes on the award, which is the time at which you get full ownership (i.e.: vesting time, for the restricted stocks). When you sell these stocks - you treat the sale as any other stock sale: you check the holding period for capital gains tax rates, and you do not pay (or get refund) any FICA taxes on the sales transaction. So bottom line: You got $10K salary and you bought $10K worth of company stock, and you sold it at $8K half a year later. You have $10K wages income and $2K short term capital loss.", "title": "" }, { "docid": "588253", "text": "I'm not a tax advisor, but I've done freelance work, so... If any of your side-business revenue is reported on a 1099, you're now a business owner, which is why Schedule C must be filled out. As a business owner, minimum wage doesn't apply to you. All revenue is income to you, and you owe taxes on the profit, after subtracting legitimate (verifiable) business expenses. You'll want to talk to a real tax advisor if you're going to start expensing mileage, part of your house (if you use a home office), etc. Don't forget that you'll owe self-employment tax (the employer's half of your payroll tax). You can't save money on business taxes by paying yourself a wage and then counting it as an expense to the business. You'll definitely want to talk to a tax expert if you start playing around with finances as an (the) owner of the business. Income that is not reported on a 1099 should be reported as hobby income.", "title": "" }, { "docid": "40044", "text": "You may also want to consider Delaware and Nevada as possible corporate homes. They are common choices for out of state corporations. You may find that they are better options. Will earnings prior to forming the LLC have to be claimed as self-employment income? If so, would it be easier to wait until the next calendar year to form the LLC? Earnings after forming the Limited Liability Corporation (LLC) will probably have to be claimed as self-employment income. See How LLC Members Are Taxed for more discussion. In particular, read the section on self-employment taxes: The current rule is that any owner who works in or helps manage the business must pay this tax on his or her distributive share (rightful share of profits). However, owners who are not active in the LLC -- that is, those who have merely invested money but don't provide services or make management decisions for the LLC -- may be exempt from paying self-employment taxes on their share of profits. The regulations in this area are a bit complicated, but if you actively manage or work in your LLC, you can expect to pay self-employment tax on all LLC profits allocated to you. As I read it, you actively work in the LLC, so it is unlikely that you can avoid paying self-employment taxes. So it shouldn't make any difference when you officially start an LLC. You'll have to pay self-employment taxes before and after creating the LLC regardless. If you don't want to pay self-employment taxes, you may want to consider forming a Subchapter C corporation. They don't have the same tax structure as Subchapter S corporations or LLCs. You would be paid some kind of wage, salary, or commission and the corporation would pay the employer's side of the payroll taxes. Note that Subchapter S corporations and LLCs exist because they usually pay less in tax than Subchapter C corporations do. Even including the self-employment taxes that you owe. A CPA should be able to guide you in making these decisions and help you with setup. The one time that I started a corporation, I just paid a few hundred dollars to a service and they filed the paperwork for me. That included state fees and notice costs. The CPA probably has a service association already.", "title": "" }, { "docid": "483489", "text": "I think you're a little confused about taxes. First, I'm guessing that you feel your lack of home ownership makes your taxes higher. That might be true, or it might not. The main tax break you would get from home ownership is the mortgage interest deduction, and that is a fraction of what you're paying in interest. So, yeah, your tax bill is lower, but 3-4 times that amount is going out the door in interest. Plus, when you buy a property, you may have substantial taxes on that property that your landlord is paying now. Secondly, yes, you can deduct expenses on a business, but that only can be done without income for so long before the IRS begins disallowing your deductions. But if you're making money, the expenses come right off of your income. Third, owning a business means that you get the privilege of paying a self-employment tax, which is the same thing that your employer now pays into Social Security on your behalf. More taxes! So in short, owning and operating a business has the potential to be more rewarding than holding down a job -- and I recommend starting up a side business just to get another income stream going -- but the tax savings really aren't that appealing to do it just for those.", "title": "" }, { "docid": "223624", "text": "Yes, you need to include income from your freelance work on your tax return. In the eyes of the IRS, this is self-employment income from your sole-proprietorship business. The reason you don't see it mentioned in the 1040EZ instructions is that you can't use the 1040EZ form if you have self-employment income. You'll need to use the full 1040 form. Your business income and expenses will be reported on a Schedule C or Schedule C-EZ, and the result will end up on Line 12 of the 1040. Take a look at the requirements at the top of the C-EZ form; you probably meet them and can use it instead of the more complicated C form. If you have any deductible business expenses related to your freelance business, this would be done on Schedule C or C-EZ. If your freelance income was more than $400, you'll also need to pay self-employment tax. To do this, you file Schedule SE, and the tax from that schedule lands on form 1040 Line 57.", "title": "" }, { "docid": "79411", "text": "\"This is not an end-all answer but it'll get you started I have been through accounting courses in college as well as worked as a contractor (files as sole proprietor) for a few years but IANAA (I am not an accountant). Following @MasonWheeler's answer, if you're making that much money you should hire a bean counter to at least overlook your bookkeeping. What type of business? First, if you're the sole owner of the business you will most likely file as a sole proprietorship. If you don't have an official business entity, you should get it registered officially asap, and file under that name. The problem with sole proprietorships is liability. If you get sued, not only are your business' assets vulnerable but they can go after your personal assets too (including house/cars/etc). Legally, you and your business are considered one and the same. To avoid liability issues, you could setup a S corporation. Basically, the business is considered it's own entity and legal matters can only take as much as the business owns. You gain more protection but if you don't explicitly keep your business finances separate from your personal finances, you can get into a lot of trouble. Also, corporations generally pay out more in taxes. Technically, since the business is it's own entity you'll need to pay yourself a 'reasonable salary'. If you skip the salary and pay yourself the profits directly (ie evade being taxed on income/salary) the IRS will shut you down (that's one of the leading causes of corporations being shut down). You can also pay distribute bonuses on top of that but it would be wise to burn the words 'within reason' into your memory first. The tax man gets mad if you short him on payroll taxes. S corporations are complicated, if you go that route definitely seek help from an accountant. Bookkeeping If you're not willing to pay a full time accountant you'll need to do a lot of studying about how this works. Generally, even if you have a sole proprietorship it's best to have a separate bank account for all of your business transactions. Every source/drain of money will fall into one of 3 categories... Assets - What your business owns: Assets can be categorized by liquidity. Meaning how fast you can transform them directly into cash. Just because a company is worth a lot doesn't necessarily mean it has a lot of cash. Some assets depreciate (lose value over time) whereas some are very hard to transform back into cash based on the value and/or market fluctuations (like property). Liabilities - What you owe others and what others owe you: Everything you owe and everything that is owed to you gets tracked. Just like credit cards, it's completely possible to owe more than you own as long as you can pay the interest to maintain the loans. Equity - the net worth of the company: The approach they commonly teach in schools is called double-entry bookkeeping where they use the equation: In practice I prefer the following because it makes more sense: Basically, if you account for everything correctly both sides of the equation should match up. If you choose to go the sole proprietorship route, it's smart to track everything I've mentioned above but you can choose to keep things simple by just looking at your Equity. Equity, the heart of your business... Basically, every transaction you make having to do with your business can be simplified down to debits (money/value) increasing and credits (money/value) decreasing. For a very simple company you can assess this by looking at net profits. Which can be calculated with: Revenues, are made up of money earned by services performed and goods sold. Expenses are made up of operating costs, materials, payroll, consumables, interest on liabilities, etc. Basically, if you brought in 250K but it cost you 100K to make that happen, you've made 150K for the year in profit. So, for your taxes you can count up all the money you've made (Revenues), subtract all of the money you've paid out (Expenses) and you'll know how much profit you've made. The profit is what you pay taxes on. The kicker is, there are gray areas when it comes to deducting expenses. For instance, you can deduct the expense of using your car for business but you need to keep a log and can only expense the miles you traveled explicitly for business. Same goes for deducting dedicated workspaces in your house. Basically, do the research if you're not 100% sure about a deduction. If you don't keep detailed books and try to expense stuff without proof, you can get in trouble if the IRS comes knocking. There are always mythical stories about 'that one guy' who wrote off his boat on his taxes but in reality, you can go to jail for tax fraud if you do that. It comes down to this. At the end of the year, if your business took in a ton of money you'll owe a lot in taxes. The better you can justify your expenses, the more you can reduce that debt. One last thing. You'll also have to pay your personal federal/state taxes (including self-employment tax). That means medicare/social security, etc. If this is your first foray into self-employment you're probably not familiar with the fact that 1099 employers pick up 1/2 of the 15% medicare/social security bill. Typically, if you have an idea of what you make annually, you should be paying this out throughout the year. My pay as a contractor was always erratic so I usually paid it out once/twice a year. It's better to pay too much than too little because the gov't will give you back the money you overpaid. At the end of the day, paying taxed sucks more if you're self-employed but it balances out because you can make a lot more money. If as you said, you've broken six figures, hire a damn accountant/adviser to help you out and start reading. When people say, \"\"a business degree will help you advance in any field,\"\" it's subjects like accounting are core requirements to become a business undergrad. If you don't have time for more school and don't want to pay somebody else to take care of it, there's plenty of written material to learn it on your own. It's not rocket surgery, just basic arithmetic and a lot of business jargon (ie almost as much as technology).\"", "title": "" }, { "docid": "35810", "text": "Making a game is hard enough, focus on that. If/when you start getting close to having something to sell, then if you're serious and want the company to grow into a full time venture, briefly consult with a lawyer and possibly accountant to set this up. It will save you a lot of time researching what you have to do and a lot of headache from potentially doing things wrong. If you want to try to do it on your own, I'd recommend getting a book on starting a business because there is more to know than a single post can cover. You'll probably have to file for a DBA (doing business as) at your city hall in order to be allowed to refer to yourself as the name of your company (otherwise you have to use your personal name). Initiating that will likely initiate annual business taxes in your town in addition to the cheap filing fee. You also want to consider how you will handle trademark (of your business and game) and copyright (of your game). If this is going to grow, you'll have to have contracts written for either employees or for freelancers who might produce assets for you. You may also need to consider writing an EULA for your game, privacy policies, etc. Additionally, you'll likely have to file with your state to collect and send sales tax. You'll also want to meticulously track costs and revenue related to your business. Formally starting a business will likely open you up to property, sales and income tax. For example, where I am, was even taxed on the equipment the business uses (e.g. computers). This is why it makes sense to wait until you're closer to having a product before you try to formally start a business and to consult with professionals on the best way. The type of business you should form will depend on the scope you plan for the company and the amount of time/money you're willing to put in. A sole proprietorship (what you are by default) means there is no difference legally/financially between you as an individual and you as a company. This may be suitable if this is just a hobby, but not if you intend it to grow because that means any lawsuit directed at your company and its money is also directed at you and your money. The differences between an LLC and corporation are more nuanced and involve differences in legal and tax treatment, however, they both shield you from the previously mentioned problem. If you want this to be more than a hobby you should form either an LLC or a corporation. Do some research on the differences and how they might apply to you and in your state.", "title": "" }, { "docid": "428533", "text": "\"If you have income - it should appear on your tax return. If you are a non-resident, that would be 1040NR, with the eBay income appearing on line 21. Since this is unrelated to your studies, this income will not be covered by the tax treaties for most countries, and you'll pay full taxes on it. Keep in mind that the IRS may decide that you're actually having a business, in which case you'll be required to attach Schedule C to your tax return and maybe pay additional taxes (mainly self-employment). Also, the USCIS may decide that you're actually having a business, regardless of how the IRS sees it, in which case you may have issues with your green card. For low income from occasional sales, you shouldn't have any issues. But if it is something systematic that you spend significant time on and earn significant amounts of money - you may get into trouble. What's \"\"systematic\"\" and how much is \"\"significant\"\" is up to a lawyer to tell you.\"", "title": "" }, { "docid": "358196", "text": "One significant reason it makes sense for filing to be the default is home ownership rates. I think far more so than investment income, Americans own homes: as there is a significant mortgage interest deduction, between that and investments a large number of Americans would have to file (about a third of Americans get the mortgage interest tax deduction, and a large chunk of the richest don't qualify but would have to file for investments anyway). We also have a very complicated tax code, with nearly everyone getting some kind of deduction. Earned Income Tax Credit for the working poor (folks making, say, $30k for a family of 4 with a full-time job get several thousand dollars in refundable credits, for example), the Student Loan interest deduction, the above mortgage deduction, almost everyone gets something. Finally, your employer may not know about your family situation. As we have tax credits and deductions for families based on number of children, for example, it's possible your employer doesn't know about those (if you don't get health insurance on their behalf, they may well not know). Start reporting things like that separately... and you end up with about as much work as filing is now.", "title": "" }, { "docid": "338582", "text": "Checkout the worksheet on page 20 of Pub 535. Also the text starting in the last half of the third column of page 18 onward. https://www.irs.gov/pub/irs-pdf/p535.pdf The fact that you get a W-2 is irrelevant as far as I can see. Your self-employment business has to meet some criteria (such as being profitable) and the plan needs to be provided through your own business (although if you're sole proprietor filing on Schedule C, it looks like having it in your own name does the trick). Check the publication for all of the rules. There is this exception that would prevent many people with full-time jobs on W-2 from taking the deduction: Other coverage. You cannot take the deduction for any month you were eligible to participate in any employer (including your spouse's) subsidized health plan at any time during that month, even if you did not actually participate. In addition, if you were eligible for any month or part of a month to participate in any subsidized health plan maintained by the employer of either your dependent or your child who was under age 27 at the end of 2014, do not use amounts paid for coverage for that month to figure the deduction. (Pages 20-21). Sounds like in your case, though, this doesn't apply. (Although your original question doesn't mention a spouse, which might be relevant to the rule if you have one and he/she works.) The publication should help. If still in doubt, you'll probably need a CPA or other professional to assess your individual situation.", "title": "" }, { "docid": "470066", "text": "You said your mother-in-law lives with you. Does she pay rent, or are you splitting the cost of housing? That would also have to figured into the equation. If you had a business you would now have to declare the expense on your business taxes. This would also then be income for her, which she would have to account for on her taxes. Remember there are both state and federal taxes involved. Regarding expenses like diapers. If the MIL had the business she could deduct them as a business expense. If you have the business it would greatly complicate the taxes. Your business would be essentially covering your personal expenses. If your MIL was not a business the cost of diapers would be paid by you regardless of the working situation of you and your spouse. To claim the tax credit: You must report the name, address, and taxpayer identification number (either the social security number, or the employer identification number) of the care provider on your return. If the care provider is a tax-exempt organization, you need only report the name and address on your return. You can use Form W-10 (PDF), Dependent Care Provider's Identification and Certification, to request this information from the care provider. If you do not provide information regarding the care provider, you may still be eligible for the credit if you can show that you exercised due diligence in attempting to provide the required information. The IRS will be looking for an income tax form from your MIL that claims the income. Getting too cute with the babysitting situation, by starting a business just for the purpose of saving money on taxes could invite an audit. Also it is not as if you just claim 3000 and you are good to go. You can only claim a percentage of the expenses based on the household AGI, the more the make the more you have to have in expenses to get the full 3000 credit, which mil cause more taxes for your MIL. Plus the whole issue with having to pay social security and other taxes on a household employee. It might be best to skip the risk of the audit. Claiming your MIL as a dependent might just be easier.", "title": "" }, { "docid": "592780", "text": "How realistic is it that I will be able to get a home within the 250,000 range in the next year or so? Very unlikely in the next year. The debt/income ratio isn't good enough, and your credit score needs to show at least a year of regular payments without late or default issues before you can start asking for mortgages in this range. You don't mention how long you've been employed at these incomes, this can also count against you if you haven't both been employed for a full year at these incomes. They will look even more unfavorably on the employment situation if they aren't both full time jobs, although if you have a full year's worth of paychecks showing the income is regular then that might mitigate the full time/part time issue. next year or so? If you pay down your high interest debt (car, credit cards), and maintain employment (keep your check stubs and tax returns, the loan officer will want copies), then there's a slight chance. And, from this quick snap shot of our finances, does it look like we would be able to qualify for a USDA loan? Probably not. Mostly for the same reasons - the only time a USDA loan helps is when you would be able to get a regular loan if you had the down payment. Even with an available down payment of 50k, you wouldn't be able to get a regular loan, therefore it's unlikely that you'd qualify for a USDA loan. If you are anxious to get into a house, choose something much smaller, in the 100k-150k range. It would improve your debt/loan ratio enough that you might then qualify for a USDA loan. However, I think you'd still have issues if you haven't both been employed at this rate of income for at least a year, and have made regular payments on all your debts for at least a year. I'll echo what others have suggested, though, strengthen your credit, eliminate as much of your high interest debt as you can (car, credit cards), and keep your jobs for a year or two. Start a savings plan so you can contribute a small down payment - at least 3-5% of the desired home price - when you are in a better position to buy. During this time keep track of your paycheck stubs, you may need them to prove income over the time period your loan officer will request. Note that even with a USDA loan you still have to pay closing costs, and those can run several thousand dollars, so don't expect to be able to come to the table with no cash. Lastly, there's good reason to be very conservative regarding house cost and size. If you can, consider buying the house as if you only had the 46k per year. Move the debt to the person making the lower income, and if you buy the house in the name of the person only making 46k per year, then the debt/loan ratio looks very positive. Further it may be that the credit history of that person is better, and the employment history is better. If one of you has better history in these ways, then you might have a better chance if only one of you buys the house. Banks can't tell you about this, but it does work. Keep in mind, though, that if you two part ways it could be very unhappy since one would be left with all the debt and the house would be in the other's name. Not a great situation to be in, so make sure that you both carefully consider the risks associated with the decisions made.", "title": "" }, { "docid": "477476", "text": "Welcome to the wonderful but oft confusing world of self-employment. Your regular job will withhold income for you and give you a W2, which tells you and the government how much is withheld. At the end of the year uber will give you and the government a 1099-misc, which will tell you how much they paid you, but nothing will be withheld, which means you will owe the government some taxes. When it comes to taxes, you will file a 1040 (the big one, not a 1040EZ nor 1040A). In addition you will file a schedule C (self-employed income), where you will report the gross paid to you, deduct your expenses, and come up with your profit, which will be taxable. That profit goes into a line in the 1040. You need to file schedule SE. This says how much self-employment tax you will pay on your 1099 income, and it will be more than you expect. Self employment tax is SS/Medicare. There's a line for this on the 1040 as well. You can also deduct half of your self-employment tax on the 1040, there's a line for it. Now, you can pay quarterly taxes on your 1099 income by filing 1040-ES. That avoids a penalty (which usually isn't that large) for not withholding enough. As an alternative, you can have your regular W2 job withhold extra. As long as you don't owe a bunch at tax time, you won't be a fined. When you are self-employed your taxes aren't as simple. Sorry. You can either spend some time becoming an expert by studying the instructions for the 1040, pay for the expensive version of tax programs, or hire someone to do it for you. Self-employed taxes are painful, but take advantage of the upsides as well. You can start a solo 401(k) or SEP IRA, for example. Make sure you are careful to deduct every relevant business expense and keep good records in case you get audited.", "title": "" }, { "docid": "588029", "text": "\"Let's pretend that the author of that article is not selling anything and is trying to help you succeed in life. I have nothing against sales, but that author is throwing out a lot of nonsense to sell his stuff and is creating a state of urgency so that people adopt this mindset. It's clever and it obviously works. From a pure time perspective, most people won't make enough money to run their own business and be as profitable as if they worked for a company. This is a reality that few want to acknowledge. If you invested in yourself and your career with the same discipline and urgency as an entrepreneur, most people would be better off at a company when you consider the benefits and the fact that employees have a full 7.5% of social security paid by their employer (entrepreneurs see the full 15% while employees don't). Why do I start here, because this author isn't telling you that the more people take his advice, the more their earnings will regress to the mean or below. In fact, most of my entrepreneur friends have to go back to work when their reality fails after they burn through their savings. 401ks are not a perfect system, but there are more 401k millionaires now than ever before this, and people who give the author's advice are always looking to avoid doing what they need to do - save for retirement. Most people I know sadly realize this in their 50s, when it's too late, and start trying to \"\"catch up.\"\" I don't blame the author for this, as he knows his article will appeal to younger people who don't have the wisdom to see that his advice hasn't been great for most. The reality is that for most people 401ks will provide tax advantaged savings that you can use when you're older; taxes will eat at your earnings, so these accounts really help. Finally, look at the article again especially the part you quote. He says inflation will carve out what you save, yet inflation is less than 2%. Where is he getting this from? In the past decade, we've seen numerous deflationary spirals and the market overall has come back from the fall in 2009. Again, this isn't \"\"good enough\"\" for this author, so buy his stuff to learn how to succeed! There have been numerous decades (50s,70s) that were much worse for investors than this past one.\"", "title": "" }, { "docid": "136315", "text": "\"Also within Germany the tax offices usually determine which tax office is responsible for you by asking where you were more than 180 days of the year (if e.g. you have a second flat where you work). That's a default value, though: in my experience you can ask to be handled by another tax office. E.g. I hand my tax declaration to my \"\"home\"\" tax office (where also my freelancing adress is), even though my day-job is 300 km away. So if you work mostly from Poland and just visit the German customer a few times, you are fine anyways. Difficulties start if you move to Germany to do the work at your customer's place. I'm going to assume that this is the situation as otherwise I don't think the question would have come up. Close by the link you provided is a kind of FAQ on this EU regulation About the question of permanent vs. temporary they say: The temporary nature of the service is assessed on a case-by-case basis. Here's my German-Italian experience with this. Background: I had a work contract plus contracts for services and I moved for a while to Italy. Taxes and social insurance on the Italian contracts had to be paid to Italy. Including tax on the contract for services. Due to the German-Italian tax treaty, there is no double taxation. Same for Poland: this is part of EU contracts. By the way: The temporary time frame for Italy seemed to be 3 months, then I had to provide an Italian residence etc. and was registered in the Italian health care etc. system. Due to the German-Italian tax treaty, there is no double taxation. Same for Poland: this is part of EU contracts. Besides that, the German tax office nevertheless decided that my \"\"primary center of life\"\" stayed in Germany. So everything but the stuff related to the Italian contracts (which would probably have counted as normal work contracts in Germany, though they is no exact equivalent to those contract types) was handled by the German tax office. I think this is the relevant part for your question (or: argumentation with the German tax office) of temporary vs. permanent residence. Here are some points they asked: There is one point you absolutely need to know about the German social insurance law: Scheinselbständigkeit (pretended self-employment). Scheinselbständigkeit means contracts that claim to be service contracts with a self-employed provider who is doing the work in a way that is typical for employees. This law closes a loophole so employer + employee cannot avoid paying income tax and social insurance fees (pension contributions and unemployment insurance on both sides - health insurance would have to be paid in full by the self-employed instead of partially by the employer. Employer also avoids accident insurance, and several regulations from labour law are avoided as well). Legally, this is a form of black labour which means that the employer commits a criminal offense and is liable basically for all those fees. There is a list of criteria that count towards Scheinselbständigkeit. Particularly relevant for you could be\"", "title": "" }, { "docid": "379546", "text": "It sounds like you are interested in investing in the stock market but you don't want to take too much risk. Investing in an Index EFT will provide some diversification and can be less risky than investing in individual stocks, however with potentially lower returns. If you want to invest your money, the first thing you should do is learn about managing your risk. You are still young and you should spend your time now to increase your education and knowledge. There are plenty of good books to start with, and you should prepare an investment plan which incorporates a risk management strategy. $1000 is a little low to start investing in the stock market, so whilst you are building your education and preparing your plan, you can continue building up more funds for when you are ready to start investing. Place your funds in an high interest savings account for now, and whilst you are learning you can practice your strategies using virtual accounts. In fact the ASX has a share market game which is held 2 or 3 times per year. The ASX website also has some good learning materials for novices and they hold regular seminars. It is another good source for improving your education in the subject. Remember, first get educated, then plan and practice, and then invest.", "title": "" } ]
5a895ba45542993b751ca92f	Which American luxury department store, owned by one of the oldest commercial corporations in North America, did the Waterside Shops have in 1992 as an anchor tenant?	[ { "docid": "29483", "text": "Saks Fifth Avenue is an American luxury department store owned by the oldest commercial corporation in North America, the Hudson's Bay Company. Its main flagship store is located on Fifth Avenue in Midtown Manhattan, New York City.", "title": "" }, { "docid": "11303991", "text": "The Waterside Shops is an upscale open-air mall located on Tamiami Trail in Pelican Bay, Florida, just to the north of Naples, Florida. Opened in 1992, the mall features Nordstrom (formerly Jacobson's) and Saks Fifth Avenue as anchor tenants. The mall opened with 85% of its retail space leased. Since 2003, the mall has been managed by the Southfield, Michigan-based Forbes Company, which also operates several other upscale malls in Michigan and Florida. Its open-air concourses feature waterfalls and landscaping.", "title": "" } ]	[ { "docid": "3484891", "text": "In retail, an anchor store, draw tenant, anchor tenant, or key tenant is one of the larger stores in a shopping mall, usually a department store or a major retail chain.", "title": "" }, { "docid": "1083210", "text": "Lord & Taylor is the oldest luxury department store in the United States, headquartered in New York City. It is a subsidiary of the oldest commercial corporation in North America, the Hudson's Bay Company.", "title": "" }, { "docid": "11784779", "text": "North Shore Square is a 621192 sqft shopping mall in Slidell, Louisiana. The mall is the largest mall on the Northshore of Lake Pontchartrain, fifth largest in the New Orleans area and the 11th largest in Louisiana. The mall is home to two anchor stores, Dillard's, and At Home, as well as approximately 23 other stores. All the anchor stores are on one level. The mall did not flood during Hurricane Katrina and experienced no serious damage. The mall formerly had Mervyns as an anchor store, but closed shortly after the storm when Mervyn's pulled out of the Louisiana market. The store was eventually replaced by Burlington Coat Factory, which is now closed due to corporate downsizing. JCPenney closed on July 31, 2017. The mall has struggled partially due to increased internet-based sales as well as an open-air shopping center located on the opposite side of town, to which it lost some of its tenants. Following a nationwide trend, the mall's future is uncertain as many former mall-based stores have either closed completely or downsized nationally, and enclosed shopping malls across the country are challenged by new consumer trends and shifting paradigms.", "title": "" }, { "docid": "44501296", "text": "ABQ Uptown is an outdoor luxury shopping mall owned by Simon Property Group in Albuquerque, New Mexico. It is one of four malls located in the Albuquerque area, and houses 46 different stores. Its anchor tenants include J.Crew, The North Face, and Lush. The outdoor environment of this mall includes music, lights and seasonal decorations.", "title": "" }, { "docid": "51472232", "text": "International Market Place is an open-air shopping center located in Waikīkī on the island of O‘ahu. It first opened in 1956 as a commercial retail and entertainment center. On August 25, 2016, the International Market Place reopened as a modern shopping, dining and entertainment center, offering 345,000 square-feet of retailers and restaurants. Its tenants include approximately 90 stores and 10 restaurants. Its anchor tenant is a three-level, 80,000-square-foot Saks Fifth Avenue, which is the department store’s only full-line Hawai‘i location.", "title": "" }, { "docid": "9878416", "text": "Quail Springs Mall is a super regional shopping mall and trade area located in far northern Oklahoma City, Oklahoma. It contains three major department store anchors, a 24-screen AMC Theatre, and a total of 130 tenants comprising a total of approximately 1,115,000 square feet of gross leasable area. The mall is the focal point of a large area of recent residential and commercial development, and is located very close to one of Oklahoma City's most notoriously congested and difficult intersections which includes West Memorial Road, North Pennsylvania Avenue and The Kilpatrick Turnpike.", "title": "" }, { "docid": "37665651", "text": "Dort Mall (formerly Small Mall and Mid-America Plaza) is a shopping mall located in Flint, Michigan. It was built in two stages in 1964 and 1965, three years before Courtland Center and five years before Genesee Valley Center, making it the oldest mall in Genesee County. It is owned by the Perani family, who also owns Perani's Hockey World, which along with Bargain Hunterz (now closed) and City Market, is one of the mall's anchor tenants.", "title": "" }, { "docid": "20033142", "text": "Century Plaza was an enclosed shopping mall in Birmingham, Alabama, United States. Opened in 1975, the mall originally included four anchor stores and more than one hundred tenants, but lost three of those anchors (JCPenney, Belk and Rich's-Macy's) in the mid-2000s. In May 2009, the mall was completely closed as Sears and the rest of the stores in the mall closed. The mall was managed by General Growth Properties of Chicago, Illinois at the time of its closure. It is now owned by the Howard Hughes Corporation. On January 3, 2012 they made the proposal that the mall should be turned into a jail and court facility.", "title": "" }, { "docid": "8017967", "text": "The Avenues is an indoor shopping mall located on the southside of Jacksonville, Florida at the intersection of U.S. 1 (Philips Highway) and Southside Boulevard near Interstate 95. The mall opened in 1990 with four anchor stores; Maison Blanche, Dillard's, JCPenney and Sears. Maison Blanche became Gayfers in 1992 which later became Belk in 1998. A Parisian department store was built in 1994. The mall, owned by Simon Property Group, has two shopping levels and features a parking garage on the north side of the complex. Some of the 150 stores inside of the mall include: Banana Republic, H&M, LOFT, Brookstone, MAC, Jos. A. Bank, The Buckle, The Body Shop, Teavana, and The Walking Company.", "title": "" }, { "docid": "6550780", "text": "Westfield Century City, formerly known as Century Square Shopping Center, is a two-level, 900,000-square-foot outdoor shopping mall in the Century City commercial district in Los Angeles, California. It is owned by Westfield Corporation. Its anchor stores include Bloomingdale's, Macy's, a Gelson's supermarket, and a 15-screen AMC multiplex. It is currently undergoing an $800 million expansion, which will add a Nordstrom flagship store.", "title": "" }, { "docid": "12007757", "text": "The Brunswick Shopping Centre, with over 30 shops, is in the centre of Scarborough, North Yorkshire, England. It was built on the site of a former Debenhams store, which is still an anchor tenant. It has an annual footfall of approximately 7 million people.", "title": "" }, { "docid": "3869610", "text": "Rhodes Waterside is located in the suburb of Rhodes, New South Wales. The centre's anchor tenants include IKEA, a Reading 8-cinema complex, Coles supermarket and Target. There are also about 100 speciality shops, professional offices and a medical centre.", "title": "" }, { "docid": "32759990", "text": "Schuylkill Mall was a shopping mall located in Frackville, Pennsylvania. Built in 1980 by Crown American, the mall originally featured Kmart, Hess's, and Sears as its anchor stores; later additions to the mall included Pomeroy's (which was later bought out by The Bon-Ton) and Phar-Mor. After losing a large number of tenants throughout the 21st century, the mall has become increasingly vacant, and as of 2017 has only Dunham's Sports as a major anchor tenant. The center is owned by Northpoint Development, who bought it out of Chapter 7 bankruptcy in 2017.", "title": "" }, { "docid": "7233284", "text": "Woodland Mall is an enclosed super-regional shopping mall located in Kentwood, Michigan, a suburb of Grand Rapids. It comprises over 100 tenants in 1158942 sqft of retail space, with three anchor stores (Macy's, JCPenney, and Barnes & Noble), along with Forever 21 (which is the largest non-anchor store in the mall), H&M, Gap (featuring Gap men, women, kids and baby), Pottery Barn, and The North Face as junior anchors and a movie theater (opened as Cinemark, now Celebration Cinema). The mall is owned and managed by Pennsylvania Real Estate Investment Trust, who acquired it from its developer, Taubman Centers, in 2006.", "title": "" }, { "docid": "38076532", "text": "Temple Mall is a regional shopping mall and trade area located in Temple, Texas. It contains four major department store anchors, and a total of 57 tenants comprising a total of approximately 555,400 square feet of gross leasable area. Anchor stores include Dillard's, IMAX, JCPenney, and Macy's", "title": "" }, { "docid": "39116878", "text": "Majura Park Shopping Centre is a big-box type shopping centre developed by Canberra Airport as part of the Majura Park precinct. The shopping centre, which opened in 2012, is part of a larger office and retail precinct on the airport's western boundary, adjacent to Majura Road. At the time of opening, the centre boasted Australia's largest Woolworths supermarket. The centre is also anchored by discount department store Big W and Toys \"R\" Us (including Babies \"R\" Us). In addition to the anchor tenants, there are over 30 specialty stores representing a variety of national chains, a 256-seat food court and Lollipop's Playland and Cafe - an air-conditioned, fully supervised children's playground.", "title": "" }, { "docid": "49636370", "text": "River Oaks District is an outdoor shopping complex of global luxury brands in the Uptown area of Houston, Texas, comprising 252,000 square feet of retail space with boutique styled shops, restaurants, sidewalk cafes, and an iPic movie theater among an expanding list of tenants. Additionally, there is 92,000 square feet of office space and two 5-story buildings with 279 residential apartments called Grey House, in the 650,000 square foot mixed-use development. River Oaks District was developed and is managed by commercial real estate firm OliverMcMillan, LLC. The design team included architectural firms Gensler, Pappageorge Haymes and the landscape architecture firm of Hoerr Schaudt. Instead of a large anchor store, the developers opted for multiple smaller, high-end anchors.", "title": "" }, { "docid": "18573944", "text": "Mall at Barnes Crossing is a super regional shopping mall located northeast of downtown Tupelo, Mississippi. It is managed and partially owned by David Hocker & Associates and is home to over 90 specialty shops, 5 anchor store tenants, an 8-screen Cinemark movie theater, and a 600-seat food court. Anchor stores include two Belk locations, as well as JCPenney, Sears, Barnes & Noble, and Dick's Sporting Goods.", "title": "" }, { "docid": "8964480", "text": "Everett Mall is a 673000 sqft indoor/outdoor shopping mall located in Everett, Washington, USA. Planned in the late 1960s, the mall began with the construction of two anchor stores, Sears in 1969 and White Front in 1971. The mall was originally built and opened in 1974 after the Boeing bust stalled construction in 1972. It was further plagued upon opening with one anchor store closing before opening as well as a low tenant rate. The mall began to rebound after The Bon Marche opened in 1977, leading to the construction of an additional wing to the mall anchored by the upscale Frederick & Nelson department store.", "title": "" }, { "docid": "7041208", "text": "The Eastfield Mall is a shopping mall in Springfield, Massachusetts, and is owned by Mountain Development Corporation. Built in late 1967 by the Rouse Company, it includes one anchor store: Sears and is also anchored by a 16 screen movie cinema owned by Cinemark. The former anchors, JCPenney and Macy's, closed in 2011 and 2016, respectively. The mall is managed by Mountain Development.", "title": "" }, { "docid": "19636117", "text": "Charleston Town Center is an enclosed shopping mall in downtown Charleston, West Virginia, United States, with large portions converted into office space. One of the largest enclosed malls to be located in a downtown shopping district, it comprises more than 130 tenants on two levels, as well as a food court on a partial third level. Popular full-service restaurants include Chili's Bar & Grill, the Chop House, Outback Steakhouse and Tidewater Grill. Anchor stores are JCPenney and Macy's. The mall is owned by Forest City Enterprises, but on March 8, 2017 a pending sale to Australia's Queensland Investment Corporation was announced.", "title": "" }, { "docid": "1925975", "text": "Southdale Center is a shopping mall located in Edina, Minnesota, a suburb of the Twin Cities. It opened in 1956 and is one of the oldest fully enclosed shopping malls, and the first climate-controlled one, in the United States. Southdale Center comprises 1300000 sqft of leasable retail space, and contains approximately 123 retail tenants. The mall is partially owned by Simon Property Group and is anchored by Herberger's and Macy's.", "title": "" }, { "docid": "6550048", "text": "The Shops at North Bridge, once known as \"Westfield North Bridge\", is an upscale, urban retail-entertainment district in Chicago, Illinois, located at 520 N. Michigan Avenue. Its anchor store is a Nordstrom; other tenants include Lego Store and Sephora. Its name alludes first to its location within the nine-block North Bridge complex and to the literal distinction of the shopping center incorporating four-level enclosed bridges over both east Grand Ave, and north Rush Street. When Westfield owned the mall, confusingly, \"Westfield North Bridge\" typically refers only to the enclosed mall, but Westfield holds a retail management contract for the entire North Bridge complex, which includes another multistory retail complex (two blocks north, at 600 N. Michigan Avenue) built in 1995 and street-level retail spaces throughout the complex. North Bridge also includes five hotels (three Hilton, two Marriott), three parking garages, and two office buildings, housing the American Medical Association and Euro RSCG. Upon opening, it also included a DisneyQuest \"urban amusement park,\" since converted into a furniture store.", "title": "" }, { "docid": "36953132", "text": "Biltmore Park Town Square is an upscale shopping center opened in mid-2009 in Asheville, North Carolina with its anchors being REI, Regal Cinemas, Barnes & Noble, with lots of other small shops. It was built as an outdoor \"Town Center\" with store fronts on the outside. Although the center opened in 2009, in 2005 the stores on the site was a YMCA, and a couple of small shops which opened before the center even did. They are still found in this center.Stores like LOFT, Orvis, and Bette can be found here along with a large hotel onsite, the Hilton. Many restaurants are in the center, like, P.F. Changs, Which Wich, Travinia Italian Kitchen, Hickory Tavern, Coldstone Creamery, BTs Burger Joint, and more. With building this center, it makes it unique that above the stores are apartments and luxury condos that are 5 stories. Also surrounding neighborhoods were developed around this center. Offices are in this center to but not to many are found. There are about 25 stores.", "title": "" }, { "docid": "11332213", "text": "Walt Whitman Shops (formerly known as Walt Whitman Mall) is a luxury shopping mall located in Huntington Station, New York on Walt Whitman Road (Route 110) and New York Avenue. It has many stores including main anchors Bloomingdale's, Lord & Taylor, Macy's and Saks Fifth Avenue. The mall is owned and managed by Melvin Simon and Associates, one of the largest developers of shopping malls in the United States and owner of Long Island's largest mall, Roosevelt Field in Garden City. Suffolk County Transit, Nassau Inter-County Express and Huntington Area Rapid Transit all have bus routes that service the mall.", "title": "" }, { "docid": "43509539", "text": "The Bridges at Mint Hill is a proposed lifestyle center in Mint Hill, North Carolina, in the United States. It will be located at the intersection of Interstate 485 and Lawyers Road. The mall is owned by The Howard Hughes Corporation, with a development partnership with Childress Klein, and Kainc as the design and executive architect. The mall will be anchored by three department stores, a movie theater, a bookstore, and other retail shops and restaurants.", "title": "" }, { "docid": "6223702", "text": "The Pacific Centre is a shopping mall located in Vancouver, British Columbia, Canada, managed by Cadillac Fairview (CF) Corporation. Based on the number of stores, most of which are underground, it is the largest mall in Downtown Vancouver with over 100 stores and shops. Anchor stores include Holt Renfrew, Harry Rosen, H&M, and Nordstrom. The mall is directly connected to the Hudson's Bay department store, Vancouver Centre Mall, two SkyTrain subway stations, and the Four Seasons Hotel Vancouver.", "title": "" }, { "docid": "8950162", "text": "The Stockmann department store is a culturally significant business building and department store located in the centre of Helsinki, Finland. It is one of many department stores owned by the Stockmann corporation. It is the largest department store in the Nordic countries in terms of area and total sales. The store is known for carrying all the internationally recognised luxury brands, and Stockmann's enjoys a reputation as the primary high-end department store in Finland. \"Stockmannin Herkku\", the food and beverage department located at the basement level, is renowned for the quality and choice of its foodstuffs. The Stockmann logo represents a set of escalators, which are commonly, but wrongly believed represent the first escalators in Finland. The first escalators in Finland were installed in the Forum department store, Turku (1926)", "title": "" }, { "docid": "10995929", "text": "Charles Towne Square was an indoor shopping mall located in North Charleston, South Carolina opened in 1976 by developer Melvin Simon & Associates. It was most noted for its large \"town square\" style clock and children's train ride during Christmas time. The mall's tenants included original anchors Montgomery Ward, JCPenney and Edward's, a local department store which would later be sold to Kuhn's-Big K and renamed \"Big K-Edwards.\" Big K-Edwards closed and Wilson's Catalog Showrooms moved into the space. The Wilson's chain was later sold to Service Merchandise. In addition to the mall's anchors, the shopping complex also featured approximately 75 specialty stores and a General Cinemas. The mall opened with great fanfare in 1976 with a Charlestonian bi-centennial theme. Television celebrity Ed McMahon led the festivities, complete with American revolutionary war-era costumes. Other luminaries included World War II hero Mark Clark, football great Rosie Grier, and Claude Akins.", "title": "" }, { "docid": "3286139", "text": "Huntington Mall is an enclosed shopping mall in the village of Barboursville in Cabell County in the U.S. state of West Virginia. The largest mall in West Virginia, it opened in 1981 and features more than 150 retailers. Anchor stores include JCPenney, Macy's, Sears, and Dick's Sporting Goods, with one anchor space currently being renovated for HomeGoods and TJ Maxx. Other major tenants including Books-A-Million, and Old Navy. The mall is owned by Cafaro Company of Youngstown, Ohio.", "title": "" } ]
8739	Buy securities at another stock exchange	[ { "docid": "334849", "text": "In a simple statement, no doesn't matter. Checked on my trade portal, everything lines up. Same ISIN, same price(after factoring in FX conversions, if you were thinking about arbitrage those days are long gone). But a unusual phenomenon I have observed is, if you aren't allowed to buy/sell a stock in one market and try to do that in a different market for the same stock you will still not be allowed to do it. Tried it on French stocks as my current provider doesn't allow me to deal in French stocks.", "title": "" }, { "docid": "295445", "text": "Also important to keep in mind is the difference in liquidity. The stock could be very liquid in 1 exchange but not in another. When times get bad, liquidity could dry up 1 one exchange, which results in a trading discount.", "title": "" }, { "docid": "418029", "text": "\"Really arbitrage means that, currency risk aside, it shouldn't matter which exchange you buy on in price terms alone. Arbitrage will always make sure that the prices are equivalent otherwise high frequency traders can make free money off the difference. In practical terms liquidity and brokerage costs usually make trading on the \"\"home\"\" exchange more worthwhile as any limit orders etc will be filled at a better price as you will more easily find a counterparty to your trade. Obviously that will only be an issue where your quantity is significant enough to move the market on a given exchange. The volume needed to move a market is dependent upon the liquidity of the particular stock.\"", "title": "" }, { "docid": "587262", "text": "Yes, it does matter very much. There's a thing called fungible instruments. These are the instruments where it doesn't matter. E.g. most options I ever dealt with in the US are fungible no matter which US exchange you trade them on. A fungible instrument is an instrument where you buy 1 lot on exchange A, then sell 1 lot on exchange B, and as a result you have 0 lots. With another instrument, you can buy 1 lot on exchange A, sell 1 lot on exchange B, and even tough they are the exact same thing, you now own 1, and owe 1 - they don't cancel each other out. Other than that, in different countries there are obviously different laws and regulations. For a small at home trader who just gambles for fun and isn't interested in negative positions (sell what you don't have), there isn't much of a difference . I think that's what the other answers are saying.", "title": "" }, { "docid": "243140", "text": "Different exchanges sometimes offer different order types, and of course have different trading fees. But once a trade is finished, it should not matter where it was executed.", "title": "" } ]	[ { "docid": "53041", "text": "\"A \"\"market maker\"\" is someone that is contractually bound, by the exchange, to provide both bid and ask prices for a given volume (e.g. 5000 shares). A single market maker usually covers many stocks, and a single stock is usually covered by many market makers. The NYSE has \"\"specialists\"\" that are market makers that also performed a few other roles in the management of trading for a stock, and usually a single issue on the NYSE is covered by only one market maker. Market makers are often middlemen between brokers (ignoring stuff like dark pools, and the fact that brokers will often trade stocks internally among their own clients before going to the exchange). Historically, the market makers gave up buy/sell discretion in exchange for being the \"\"go-to guys\"\" for anyone wanting to trade in that stock. When you told your broker to buy a stock for you, he didn't hook you up with another retail investor; he went to the market maker. Market makers would also sometimes find investors willing to step in when more liquidity was needed for a security. They were like other floor traders; they hung out on the exchange floors and interacted with traders to buy and sell stocks. Traders came to them when they wanted to buy one of the specialist's issues. There was no public order book; just ticker tape and a quote. It was up to the market maker to maintain that order book. Since they are effectively forbidden from being one-sided traders in a security, their profit comes from the bid-ask spread. Being the counter-party to almost every trade, they'd make profit from always selling above where they were buying. (Except when the price moved quickly -- the downside to this arrangement.) \"\"The spread goes to the market maker\"\" is just stating that the profit implicit in the spread gets consumed by the market maker. With the switch to ECNs, the role of the market maker has changed. For example, ForEx trading firms tend to act as market makers to their customers. On ECNs, the invisible, anonymous guy at the other end of most trades is often a market maker, still performing his traditional role. Yet brokers can interact directly with each other now, rather than relying on the market maker's book. With modern online investing and public order books, retail investors might even be trading directly with each other. Market makers are still out there; in part, they perform a service sold by an Exchange to the companies that choose to be listed on that exchange. That service has changed to helping tamp volatility during normal high-volatility periods (such as at open and close).\"", "title": "" }, { "docid": "332924", "text": "\"I recommend avoiding trading directly in commodities futures and options. If you're not prepared to learn a lot about how futures markets and trading works, it will be an experience fraught with pitfalls and lost money – and I am speaking from experience. Looking at stock-exchange listed products is a reasonable approach for an individual investor desiring added diversification for their portfolio. Still, exercise caution and know what you're buying. It's easy to access many commodity-based exchange-traded funds (ETFs) on North American stock exchanges. If you already have low-cost access to U.S. markets, consider this option – but be mindful of currency conversion costs, etc. Yet, there is also a European-based company, ETF Securities, headquartered in Jersey, Channel Islands, which offers many exchange-traded funds on European exchanges such as London and Frankfurt. ETF Securities started in 2003 by first offering a gold commodity exchange-traded fund. I also found the following: London Stock Exchange: Frequently Asked Questions about ETCs. The LSE ETC FAQ specifically mentions \"\"ETF Securities\"\" by name, and addresses questions such as how/where they are regulated, what happens to investments if \"\"ETF Securities\"\" were to go bankrupt, etc. I hope this helps, but please, do your own due diligence.\"", "title": "" }, { "docid": "450760", "text": "\"I know its not legal to have open long and short position on specific security (on two stock exchanges - NSE/BSE) There is nothing illegal about it. There are prescribed ways on how this is addressed. In Cash Segment / Intra Day trades: One can short sell a security. If by end of day he does not buy the security; it goes into Auction. The said security is purchased on your behalf. Any profit or loss arising out of this is charged to you. Similarly one can buy a security; if one does not pay the amount by end of day; it would go into auction and sold. Any profit or loss arising out of this is charged to you. If you short sell a security on one exchange; you have to buy it on same exchange. If you buy on other exchange; it will not be adjusted against this short position. Also is it legal to have long position on stock and short its derivative (future/option)? There are no restrictions. Edit: @yety Party A shorts 10 shares of HDFC today in Intra-Day Cash Segment purchased by Party B. Rather than buying back 10 shares or allowing it to go into auction... Party A borrows 10 HDFC Shares from \"\"X\"\" via SLB for a period of say 6 months [1 month to 1 year]. This is recorded as Party A obligation to \"\"X\"\". These 10 borrowed shares are transferred to Party B. So Party \"\"X\"\" doesn't have any HDFC shares at this point in time. However in exchange, Party X receives fees for borrowing from Party A. If there is dividend, are declared, Company pays Party B. However SLB recovers identical amount from Party A and pays Party X. If there is 1:1 split, now party A owes Party X 20 HDFC Shares. On maturity [after 6 months], Party A has to buy these from market and given back the borrowed shares to Party X. If there are some other corporate actions, i.e. mergers / amalgamations ... the obligation of Party A to Party X is closed immediately and position settled. Of course there are provisions whereby party A can pay back the shares earlier or party X can ask for shares earlier and there are rules/trades/mechanisms to facilitate this.\"", "title": "" }, { "docid": "291903", "text": "\"Pink Sheets is not a stock exchange per se, and securities traded through it are not as \"\"safe\"\" as the ones on a stock exchange regulated by SEC. Many companies are traded there because they failed to comply with the SEC regulations, or are bankrupt or don't want the level of reporting to the public that the SEC regulations require. Since you're talking about an ADR of a company traded on LSE, it might be much safer that other, \"\"regular\"\", securities, but still it means that you're buying an unregulated security (even if it is of a company regulated elsewhere). Notice the volume of trades: mere thousands of dollars per day (in a good day, in some days there are no trades at all). It makes it harder to sell the security when needed. Why not buying at LSE?\"", "title": "" }, { "docid": "1577", "text": "If I buy VUSA from one exchange, can I sell it in a different exchange, assuming my brokerage account lets me trade in both exchanges? Or is it somehow tied to the exchange I bought it from? This doesn't happen for all securities and between all stock exchanges. So that is dependent on broker and country. I checked for VUSA with Selftrade. They categorically refused allowing me to trade in VUSA in different exchanges. I can only buy and sell in same currency only, albeit sell(buy) in the same exchange where I buy(sell) from. Should be the same behaviour for all brokers for us mere mortals, if you are a bank or a millionaire than that might be a different question. The VUSA you quote is quoted in GBP in LSE and in EUR in AEX, and the ETF has been created by an Irish entity and has an Irish ISIN. As Chris mentioned below, happens between US and Canadian exchanges, but not sure it happens across all exchanges. You cannot deal in inter-listed stocks in LSE and NYSE. Since it's the same asset, its value should not vary across exchanges once you compensate for exchange rates, right? Yes, else it opens up itself for arbitrage (profit without any risk) which everybody wants. So even if any such instance occurs, either people will exploit it to make the arbitrage profit zero (security reflects the equilibrium price) or the profit from such transaction is so less, compared with the effort involved, that people will tend to ignore it. Anyways arbitrage profit is very difficult to garner nowadays, considering the super computers at work in the market who exploit these discrepancies, the moment they see them and bring the security right to the zero arbitrage profit point. If there's no currency risk because of #2, what other factors should I consider when choosing an exchange to trade in? Liquidity? Something else? Time difference, by the time you wake up to trade in Japan, the Japanese markets would have closed. Tax implications across multiple continents. Law of the land, providing protection to investors. Finding a broker dealing in markets you want to explore or dealing with multiple brokers. Regulatory headaches.", "title": "" }, { "docid": "227232", "text": "Gold is traded on the London stock exchange (LSE) and the New York stock exchange (NYSE) under various separate asset tickers, mainly denominated in sterling and US dollars respectively. These stocks will reflect FX changes very quickly. If you sold LSE gold and foreign exchanged your sterling to dollars to buy NYSE gold you would almost certainly lose on the spreads upon selling, FX'ing and re-buying. In short, the same asset doesn't exist in multiple currencies. It may have the same International Securities Identification Number (ISIN), but it can trade with different Stock Exchange Daily Official List (SEDOL) identifiers, reflecting different currencies and/or exchanges, each carrying a different price at any one time.", "title": "" }, { "docid": "579244", "text": "Traditionally, dealers and broker-dealers were in contact with the actual producers of a product or issuers of a security, selling it at the exchange on their behalf. Consumers would traditionally be on the buy side, of course. These days, anyone can enter the market on either side. Even if you don't hold the security or product, you could sell it, and take on the risk of having to stock up on it by the delivery date in exchange for cash or other securities. On the other side, if you can't hold the product or security you could still buy it, taking on the risk of having to dispose of it somehow by delivery in exchange for cash or other securities. In either case you (the sell-side) take on risk and provide products/securities/cash. This is most commonly known as market making. Modern literature coins the terms liquidity taker (buy-side) and liquidity provider (sell-side). Even more accurately, risk management literature would use the terms risk-taker (sell-side) and risk spreader or risk reducer (buy side). This is quite illustrative in modern abstract markets. Take a market that allows for no offsetting or hedging because the product in question is abstract or theoretical, e.g. weather trading, volatility trading, inflation trading, etc. There's always one party trying to eliminate dependence on or correlation to the product (the risk reducer, buy-side) and the counterparty taking on their risk (sell-side).", "title": "" }, { "docid": "328703", "text": "Yes, depending on what you're trying to achieve. If its just a symbolic gift - you can use a service like this. There are several companies providing this service, look them up, but the prices are fairly the same. You'll end up getting a real stock certificate, but it will cost a lot of overhead (around $40 to get the certificate, and then another $40 to deposit it into a brokerage account if you want to sell it on a stock exchange). So although the certificate is real and the person whose name on it is a full-blown shareholder, it doesn't actually have much value (unless you buy a Google or Apple stock, where the price is much much higher than the fees). Take into account that it takes around 2 months for the certificate to be issued and mailed to you, so time accordingly. Otherwise, you can open a custodial brokerage account, and use it to buy stocks for the minor. Both ways are secure and legal, each for its own purpose and with its own fees.", "title": "" }, { "docid": "387141", "text": "Well, Taking a short position directly in real estate is impossible because it's not a fungible asset, so the only way to do it is to trade in its derivatives - Investment Fund Stock, indexes and commodities correlated to the real estate market (for example, materials related to construction). It's hard to find those because real estate funds usually don't issue securities and rely on investment made directly with them. Another factor should be that those who actually do have issued securities aren't usually popular enough for dealers and Market Makers to invest in it, who make it possible to take a short position in exchange for some spread. So what you can do is, you can go through all the existing real estate funds and find out if any of them has a broker that let's you short it, in other words which one of them has securities in the financial market you can buy or sell. One other option is looking for real estate/property derivatives, like this particular example. Personally, I would try to computationally find other securities that may in some way correlate with the real estate market, even if they look a bit far fetched to be related like commodities and stock from companies in construction and real estate management, etc. and trade those because these have in most of the cases more liquidity. Hope this answers your question!", "title": "" }, { "docid": "274165", "text": "As Waldfee says, CFDs are a derivative (of the underlying stock in this case). If you are from the USA then they are prohibited in the USA as has also been mentioned. They are not prohibited, however, in many other countries including Australia. We can buy or short sell (on a limited number of securities) CFDs on Australian securities, USA securities and securities from many other countries, on FX, and different commodities. The reason you are paying much less than the actial stock price is worth is because you are buying on margin. When you go long you pay interest on overnight positions, and when you go short you recieve interest on overnight positions (that is if you hold the position open overnight). Most CFDs are over the counter, however in Australia (don't know about other countries) we also have exchange traded CFDs called ASX CFDs. I have tried both ASX CFDs and over the counter CFDs and prefer the over the counter CFDs because the broker provides a market which closely but not exactly follows the underlying prices. Wlth the exchange traded CFDs there was low liquidity due to being quite new so there was the potential to be gapped quite considerably. This might improve as the market grows. All in all, once you understand how they work and what is involved in trading them, they are much easier than options or futers. However, if you are going to trade anything first get yourself educated, have a trading plan and risk management strategy, and paper trade before putting real money on the table. And remember, if you are in the USA, you are actually prohibited from trading CFDs. Regarding the price of AAPL at $50, the price should be the same as that of the underlying stock, it is just that your initial outlay will be less than buying the stock directly because you are buying on margin. Your initial outlay may be as little as 5% or lower, depending on the underlying stock.", "title": "" }, { "docid": "9116", "text": "ACWI refers to a fund that tracks the MSCI All Country World Index, which is A market capitalization weighted index designed to provide a broad measure of equity-market performance throughout the world. The MSCI ACWI is maintained by Morgan Stanley Capital International, and is comprised of stocks from both developed and emerging markets. The ex-US in the name implies exactly what it sounds; this fund probably invests in stock markets (or stock market indexes) of the countries in the index, except the US. Brd Mkt refers to a Broad Market index, which, in the US, means that the fund attempts to track the performance of a wide swath of the US stock market (wider than just the S&P 500, for example). The Dow Jones U.S. Total Stock Market Index, the Wilshire 5000 index, the Russell 2000 index, the MSCI US Broad Market Index, and the CRSP US Total Market Index are all examples of such an index. This could also refer to a fund similar to the one above in that it tracks a broad swath of the several stock markets across the world. I spoke with BNY Mellon about the rest, and they told me this: EB - Employee Benefit (a bank collective fund for ERISA qualified assets) DL - Daily Liquid (provides for daily trading of fund shares) SL - Securities Lending (fund engages in the BNY Mellon securities lending program) Non-SL - Non-Securities Lending (fund does not engage in the BNY Mellon securities lending program) I'll add more detail. EB (Employee Benefit) refers to plans that fall under the Employee Retirement Income Security Act, which are a set a laws that govern employee pensions and retirement plans. This is simply BNY Mellon's designation for funds that are offered through 401(k)'s and other retirement vehicles. As I said before, DL refers to Daily Liquidity, which means that you can buy into and sell out of the fund on a daily basis. There may be fees for this in your plan, however. SL (Securities Lending) often refers to institutional funds that loan out their long positions to investment banks or brokers so that the clients of those banks/brokerages can sell the shares short. This SeekingAlpha article has a good explanation of how this procedure works in practice for ETF's, and the procedure is identical for mutual funds: An exchange-traded fund lends out shares of its holdings to another party and charges a rental fee. Running a securities-lending program is another way for an ETF provider to wring more return out of a fund's holdings. Revenue from these programs is used to offset a fund's expenses, which allows the provider to charge a lower expense ratio and/or tighten the performance gap between an ETF and its benchmark.", "title": "" }, { "docid": "225877", "text": "Keep in mind that the exchanges do not hold, buy, or sell the stock - people (or funds) do. All the exchange does is facilitate the sale of stock from one entity to another. So the shares outstanding (and market cap) for a company are set regardless of how many exchanges the stock is listed on. The company typically indicates the number of shares outstanding in its financial statements. I do not know if the exchange itself keeps track of shares outstanding; it may just report whatever the company publishes. So theoretically, if you wanted to buy all of the stock of a company, you could do it all in one exchange, provided that all the existing holders of the stock were willing to sell you their shares. There are many issues with that, though, which I don't think are germane to your question.", "title": "" }, { "docid": "152709", "text": "\"Members of the Federal Reserve System keep track of what money a bank has (if it's not in the vault), who owns what shares of stock, who owns what bond, etc. The part of the Federal Reserve System that tracks stock ownership is the Depository Trust Company (DTC). They have a group of subsidiaries that settle various types of security transactions. DTC is a member of the U.S. Federal Reserve System, a limited-purpose trust company under New York State banking law and a registered clearing agency with the Securities and Exchange Commission. There's lots of information on their website describing this process. DTCC's subsidiary, The Depository Trust Company (DTC), established in 1973, was created to reduce costs and provide clearing and settlement efficiencies by immobilizing securities and making \"\"book-entry\"\" changes to ownership of the securities. DTC provides securities movements for NSCC's net settlements1, and settlement for institutional trades (which typically involve money and securities transfers between custodian banks and broker/dealers), as well as money market instruments. Black pools are trades done where the price is not shared with the market. But the DTC is the one who keeps track of who owns which shares. They have records of all net transactions2. The DTC is the counterparty for transactions. When stock moves from one entity to another the DTC is involved. As the central counterparty for the nation's major exchanges and markets, DTCC clears and settles virtually all broker-to-broker equity 1. This is the link that shows that settlements are reported on a \"\"net basis\"\". 2. If broker A sells 1000 shares of something to broker B at 8 and then five minutes later broker B sells the 1000 shares back to A, you cannot be sure that that total volume will be recorded. No net trading took place and there would be fees to pay for no reason if they reported both trades. Note: In dark pool trading quite often the two parties don't know each other. For shares (book-keeping records) to be exchanged it has to be done through a Clearing House.\"", "title": "" }, { "docid": "72024", "text": "\"Not all call options that have value at expiration, exercise by purchasing the security (or attempting to, with funds in your account). On ETNs, they often (always?) settle in cash. As an example of an option I'm currently looking at, AVSPY, it settles in cash (please confirm by reading the documentation on this set of options at http://www.nasdaqomxtrader.com/Micro.aspx?id=Alpha, but it is an example of this). There's nothing it can settle into (as you can't purchase the AVSPY index, only options on it). You may quickly look (wikipedia) at the difference between \"\"American Style\"\" options and \"\"European Style\"\" options, for more understanding here. Interestingly I just spoke to my broker about this subject for a trade execution. Before I go into that, let me also quickly refer to Joe's answer: what you buy, you can sell. That's one of the jobs of a market maker, to provide liquidity in a market. So, when you buy a stock, you can sell it. When you buy an option, you can sell it. That's at any time before expiration (although how close you do it before the closing bell on expiration Friday/Saturday is your discretion). When a market maker lists an option price, they list a bid and an ask. If you are willing to sell at the bid price, they need to purchase it (generally speaking). That's why they put a spread between the bid and ask price, but that's another topic not related to your question -- just note the point of them buying at the bid price, and selling at the ask price -- that's what they're saying they'll do. Now, one major difference with options vs. stocks is that options are contracts. So, therefore, we can note just as easily that YOU can sell the option on something (particularly if you own either the underlying, or an option deeper in the money). If you own the underlying instrument/stock, and you sell a CALL option on it, this is a strategy typically referred to as a covered call, considered a \"\"risk reduction\"\" strategy. You forfeit (potential) gains on the upside, for money you receive in selling the option. The point of this discussion is, is simply: what one buys one can sell; what one sells one can buy -- that's how a \"\"market\"\" is supposed to work. And also, not to think that making money in options is buying first, then selling. It may be selling, and either buying back or ideally that option expiring worthless. -- Now, a final example. Let's say you buy a deep in the money call on a stock trading at $150, and you own the $100 calls. At expiration, these have a value of $50. But let's say, you don't have any money in your account, to take ownership of the underlying security (you have to come up with the additional $100 per share you are missing). In that case, need to call your broker and see how they handle it, and it will depend on the type of account you have (e.g. margin or not, IRA, etc). Generally speaking though, the \"\"margin department\"\" makes these decisions, and they look through folks that have options on things that have value, and are expiring, and whether they have the funds in their account to absorb the security they are going to need to own. Exchange-wise, options that have value at expiration, are exercised. But what if the person who has the option, doesn't have the funds to own the whole stock? Well, ideally on Monday they'll buy all the shares with the options you have at the current price, and immediately liquidate the amount you can't afford to own, but they don't have to. I'm mentioning this detail so that it helps you see what's going or needs to go on with exchanges and brokerages and individuals, so you have a broader picture.\"", "title": "" }, { "docid": "577768", "text": "It might be easiest to think of stock exchanges like brokers. If you buy a home, and your broker goes bankrupt, you still own your home, but you could not sell it without the aid of another broker. Same with stocks, you own the stocks you buy, but you would be unable to either purchase new stocks or sell your stock holdings without an exchange.", "title": "" }, { "docid": "526661", "text": "\"Long term: Assuming you sold stock ABC through a registered stock exchange, e.g., the Bombay Stock Exchange or the National Stock Exchange of India, and you paid the Securities Transaction Tax (STT), you don't owe any other taxes on the long term capital gain of INR 100. If you buy stock BCD afterwards, this doesn't affect the long term capital gains from the sale of stock ABC. Short term: If you sell the BCD stock (or the ABC stock, or some combination therein) within one year of its purchase, you're required to pay short term capital gains on the net profit, in which case you pay the STT and the exchange fees and an additional flat rate of 15%. The Income Tax Department of India has a publication titled \"\"How to Compute your Capital Gains,\"\" which goes into more detail about a variety of relevant situations.\"", "title": "" }, { "docid": "438190", "text": "When a delisting happens, the primary process involves, the firm or the entity, trying to buy everyone out so that they can take the firm private by delisting from the stock exchanges. As the firm wants to buy everyone out, the current owners of the equity have the upper hand. They wouldn't want to sell if they believe the firm has a brighter future. So to compensate the existing holders, the buyer needs to compensate the current holders of any future loss, so they pay a premium to buy them out. Hence the prices offered will be more than the current existing price. And in anticipation of a premium the stocks price rises on this speculation. The other scenario is if the current holder(s) decide no to sell their holdings and are small in number, dependent on exchange regulations, and the buyer manages to de-list the stock, the holders might loose out i.e. they have to find another buyer who wants to buy which becomes difficult as the liquidity for the stock is very minimal. if any stock is DE-listed and then we can not trade on it, In India if the promoters capital is more than 90%, he can get the stock de-listed. There is a process, he has to make an open offer at specified price to minority shareholders. The minority shareholder can refuse to sell. Once the stock is de-listed, it means it cannot be traded on a given exchange. However you can still sell / buy by directly finding a buyer / seller and it's difficult compared to a listed stock.", "title": "" }, { "docid": "127578", "text": "Technically, of course. Almost any company can go bankrupt. One small note: a company goes bankrupt, not its stock. Its stock may become worthless in bankruptcy, but a stock disappearing or being delisted doesn't necessarily mean the company went bankrupt. Bankruptcy has implications for a company's debt as well, so it applies to more than just its stock. I don't know of any historical instances where this has happened, but presumably, the warning signs of bankruptcy would be evident enough that a few things could happen. Another company, e.g. another exchange, holding firm, etc. could buy out the exchange that's facing financial difficulty, and the companies traded on it would transfer to the new company that's formed. If another exchange bought out the struggling exchange, the shares of the latter could transfer to the former. This is an attractive option because exchanges possess a great deal of infrastructure already in place. Depending on the country, this could face regulatory scrutiny however. Other firms or governments could bail out the exchange if no one presented a buyout offer. The likelihood of this occurring depends on several factors, e.g. political will, the government(s) in question, etc. For a smaller exchange, the exchange could close all open positions at a set price. This is exactly what happened with the Hong Kong Mercantile Exchange (HKMex) that MSalters mentioned. When the exchange collapsed in May 2013, it closed all open positions for their price on the Thursday before the shutdown date. I don't know if a stock exchange would simply close all open positions at a set price, since equity technically exists in perpetuity regardless of the shutdown of an exchange, while many derivatives have an expiration date. Furthermore, this might not be a feasible option for a large exchange. For example, the Chicago Mercantile Exchange lists thousands of products and manages hundreds of millions of transactions, so closing all open positions could be a significant undertaking. If none of the above options were available, I presume companies listed on the exchange would actively move to other, more financially stable exchanges. These companies wouldn't simply go bankrupt. Contracts can always be listed on other exchanges as well. Considering the high level of mergers and acquisitions, both unsuccessful and successful, in the market for exchanges in recent years, I would assume that option 1 would be the most likely (see the NYSE Euronext/Deutsche Börse merger talks and the NYSE Euronext/ICE merger that's currently in progress), but for smaller exchanges, there is the recent historical precedent of the HKMex that speaks to #3. Also, the above answer really only applies to publicly traded stock exchanges, and not all stock exchanges are publicly-held entities. For example, the Shanghai Stock Exchange is a quasi-governmental organization, so I presume option 2 would apply because it already receives government backing. Its bankruptcy would mean something occurred for the government to withdraw its backing or that it became public, and a discussion of those events occurring in the future is pure speculation.", "title": "" }, { "docid": "14781", "text": "\"Yes, you're still exposed to currency risk when you purchase the stock on company B's exchange. I'm assuming you're buying the shares on B's stock exchange through an ADR, GDR, or similar instrument. The risk occurs as a result of the process through which the ADR is created. In its simplest form, the process works like this: I'll illustrate this with an example. I've separated the conversion rate into the exchange rate and a generic \"\"ADR conversion rate\"\" which includes all other factors the bank takes into account when deciding how many ADR shares to sell. The fact that the units line up is a nice check to make sure the calculation is logically correct. My example starts with these assumptions: I made up the generic ADR conversion rate; it will remain constant throughout this example. This is the simplified version of the calculation of the ADR share price from the European share price: Let's assume that the euro appreciates against the US dollar, and is now worth 1.4 USD (this is a major appreciation, but it makes a good example): The currency appreciation alone raised the share price of the ADR, even though the price of the share on the European exchange was unchanged. Now let's look at what happens if the euro appreciates further to 1.5 USD/EUR, but the company's share price on the European exchange falls: Even though the euro appreciated, the decline in the share price on the European exchange offset the currency risk in this case, leaving the ADR's share price on the US exchange unchanged. Finally, what happens if the euro experiences a major depreciation and the company's share price decreases significantly in the European market? This is a realistic situation that has occurred several times during the European sovereign debt crisis. Assuming this occurred immediately after the first example, European shareholders in the company experienced a (43.50 - 50) / 50 = -13% return, but American holders of the ADR experienced a (15.95 - 21.5093) / 21.5093 = -25.9% return. The currency shock was the primary cause of this magnified loss. Another point to keep in mind is that the foreign company itself may be exposed to currency risk if it conducts a lot of business in market with different currencies. Ideally the company has hedged against this, but if you invest in a foreign company through an ADR (or a GDR or another similar instrument), you may take on whatever risk the company hasn't hedged in addition to the currency risk that's present in the ADR/GDR conversion process. Here are a few articles that discuss currency risk specifically in the context of ADR's: (1), (2). Nestle, a Swiss company that is traded on US exchanges through an ADR, even addresses this issue in their FAQ for investors. There are other risks associated with instruments like ADR's and cross-listed companies, but normally arbitrageurs will remove these discontinuities quickly. Especially for cross-listed companies, this should keep the prices of highly liquid securities relatively synchronized.\"", "title": "" }, { "docid": "53993", "text": "\"A company whose stock is available for sale to the public is called a publicly-held or publicly-traded company. A public company's stock is sold on a stock exchange, and anyone with money can buy shares through a stock broker. This contrasts with a privately-held company, in which the shares are not traded on a stock exchange. In order to invest in a private company, you would need to talk directly to the current owners of the company. Finding out if a company is public or private is fairly easy. One way to check this is to look at the Wikipedia page for the company. For example, if you take a look at the Apple page, on the right sidebar you'll see \"\"Type: Public\"\", followed by the stock exchange ticker symbol \"\"AAPL\"\". Compare this to the page for Mars, Inc.; on that page, you'll see \"\"Type: Private\"\", and no stock ticker symbol listed. Another way to tell: If you can find a quote for a share price on a financial site (such as Google Finance or Yahoo Finance), you can buy the stock. You won't find a stock price for Mars, Inc. anywhere, because the stock is not publicly traded.\"", "title": "" }, { "docid": "529001", "text": "It doesn't matter which exchange a share was purchased through (or if it was even purchased on an exchange at all--physical share certificates can be bought and sold outside of any exchange). A share is a share, and any share available for purchase in New York is available to be purchased in London. Buying all of a company's stock is not something that can generally be done through the stock market. The practical way to accomplish buying a company out is to purchase a controlling interest, or enough shares to have enough votes to bind the board to a specific course of action. Then vote to sell all outstanding shares to another company at a particular fixed price per share. Market capitalization is an inaccurate measure of the size of a company in the first place, but if you want to quantify it, you can take the number of outstanding shares (anywhere and everywhere) and multiply them by the price on any of the exchanges that sell it. That will give you the market capitalization in the currency that is used by whatever exchange you chose.", "title": "" }, { "docid": "390529", "text": "\"In the US, a private company with less than 500 owners can dictate who can or can't become a shareholder (this is true in general, but I'm sure there are loopholes). Prior to Google's IPO I could not buy shares in Google at any price. The reason Google was \"\"forced\"\" to go public is the 500 shareholder rule. At a high level, with 500 shareholders the company is forced to do some extra financial accounting and they no longer can control who owns a share of the company, allowing me to purchase shares of google at that point. At that point, it typically becomes in the companies best interest to go public. See this article about Google approaching the 500 shareholder limit in 2003. Further, Sorkin is not quite correct that \"\"securities laws mandate that the company go public\"\" if by \"\"go public\"\" we mean list on a stock exchange, available for general purchase. Securities laws mandate what has to be reported in financial reporting and when you have to report it. Securities laws also can dictate restrictions on ownership of stock and if a company can impose their own restrictions. A group of investors cannot force a company onto a stock exchange. If shares of Facebook are already for sale to anyone, then having >500 shareholders will force Facebook to file more paperwork with the SEC, it won't force Facebook onto the NYSE or NASDAQ. When that point is reached, it may be in Facebook's best interest to have an IPO, but they will not be required by law to do so. Update: CNN article discusses likely Facebook IPO in 2012. When companies have more than 500 shareholders, they're required to make significant financial disclosures -- though they can choose to remain private and keep their stock from trading publicly. However, most companies facing mandatory disclosures opt to go public. The Securities and Exchange Commission gives businesses lots of time to prepare for that milestone. Companies have until 120 days after the end of the fiscal year in which they cross the 500-shareholder line to begin making their disclosures. If Facebook tips the scale this year, that gives it until April 2012 to start filing financial reports.\"", "title": "" }, { "docid": "345851", "text": "\"Cart's answer describes well one aspects of puts: protective puts; which means using puts as insurance against a decline in the price of shares that you own. That's a popular use of puts. But I think the wording of your question is angling for another strategy: Writing puts. Consider: Cart's strategy refers to the buyer of a put. But, on the transaction's other side is a seller of the put – and ultimately somebody created or wrote that put contract in the first place! That first seller of the put – that is, the seller that isn't just selling one they themselves bought – is the put writer. When you write a put, you are taking on the obligation to buy the other side's stock at the put exercise price if the stock price falls below that exercise price by the expiry date. For taking on the obligation, you receive a premium, like how an insurance company charges a premium to insure against a loss. Example: Imagine ABC Co. stock is trading at $25.00. You write a put contract agreeing to buy 100 shares of ABC at $20.00 per share (the exercise price) by a given expiration date. Say you receive $2.00/share premium from the put buyer. You now have the obligation to purchase the shares from the put buyer in the event they are below $20.00 per share when the option expires – or, technically any time before then, if the buyer chooses to exercise the option early. Assuming no early assignment, one of two things will happen at the option expiration date: ABC trades at or above $20.00 per share. In this case, the put option will expire worthless in the hands of the put buyer. You will have pocketed the $200 and be absolved from your obligation. This case, where ABC trades above the exercise price, is the maximum profit potential. ABC trades below $20.00 per share. In this case, the put option will be assigned and you'll need to fork over $2000 to the put buyer in exchange for his 100 ABC shares. If those shares are worth less than $18.00 in the market, then you've suffered a loss to the extent they are below that price (times 100), because remember – you pocketed $200 premium in the first place. If the shares are between $18.00 to $20.00, you're still profitable, but not to the full extent of the premium received. You can see that by having written a put it's possible to acquire ABC stock at a price lower than the market price – because you received some premium in the process of writing your put. If you don't \"\"succeed\"\" in acquiring shares on your first write (because the shares didn't get below the exercise price), you can continue to write puts and collect premium until you do get assigned. I have read the book \"\"Money for Nothing (And Your Stocks for FREE!)\"\" by Canadian author Derek Foster. Despite the flashy title, the book essentially describes Derek's strategy for writing puts against dividend-paying value stocks he would love to own. Derek picks quality companies that pay a dividend, and uses put writing to get in at lower-than-market prices. Four Pillars reviewed the book and interviewed Derek Foster: Money for Nothing: Book Review and Interview with Derek Foster. Writing puts entails risk. If the stock price drops to zero then you'll end up paying the put exercise price to acquire worthless shares! So your down-side can easily be multiples of the premium collected. Don't do this until and unless you understand exactly how this works. It's advanced. Note also that your broker isn't likely to permit you to write puts without having sufficient cash or margin in your account to cover the case where you are forced to buy the stock. You're better off having cash to secure your put buys, otherwise you may be forced into leverage (borrowing) when assigned. Additional Resources: The Montreal Exchange options guide (PDF) that Cart already linked to is an excellent free resource for learning about options. Refer to page 39, \"\"Writing secured put options\"\", for the strategy above. Other major options exchanges and organizations also provide high-quality free learning material:\"", "title": "" }, { "docid": "206342", "text": "While the issuer of the security such as a stock or bond not the short is responsible for the credit risk, the issuer and the short of a derivative is one. In all cases, it is more than likely that a trader is owed securities by an agent such as a broker or exchange or clearinghouse. Legally, only the Options Clearing Corporation clears openly traded options. With stocks and bonds, brokerages can clear with each other if approved. While a trader is expected to fund margin, the legal responsibility is shared by all in the agent chain. Clearinghouses are liable to exchanges. Exchanges are liable to members. Traders are liable to brokerages. Both ways and so on. Clearinghouses are usually ultimately liable for counterparty risk to the long counterparty, and the short counterparty is ultimately liable to the clearinghouse. Clearinghouses are not responsible for the credit risk of stocks and bonds because the issuers are not short those securities on the exchange, thus no margin is required. Credit risk for stocks and bonds is mitigated away from the clearing process.", "title": "" }, { "docid": "69197", "text": "Quote driven markets are the predecessors to the modern securities market. Before electronic trading and HFTs specifically, trading was thin and onerous. Today, the average investor can open up a web page, type in a security, and buy at the narrowest spread permitted by regulators with anyone else who wants to take the other side. Before the lines between market maker and speculator became blurred to indistinction, a market maker was one who was contractually obligated to an exchange to provide a bid and ask for a given security on said exchange even though at heart a market maker is still simply a trader despite the obligation. A market maker would simultaneously buy a large amount of securities privately and short the same amount to have no directional bias, exposure to the direction of the security, and commence to making the market. The market maker would estimate its cost basis for the security based upon those initial trades and provide a bid and ask appropriate for the given level of volume. If volumes were high, the spread would be low and vice versa. Market makers who survived crashes and spikes would forgo the potential profit in always providing a steady price and spread, ie increased volume otherwise known as revenue, to maintain no directional bias. In other words, if there were suddenly many buyers and no sellers, hitting the market maker's ask, the MM would raise the ask rapidly in proportion to the increased exposure while leaving the bid somewhere below the cost basis. Eventually, a seller would arise and hit the MM's bid, bringing the market maker's inventory back into balance, and narrowing the spread that particular MM could provide since a responsible MM's ask could rise very high very quickly if a lack of its volume relative to its inventory made inventory too costly. This was temporarily extremely costly to the trader if there were few market makers on the security the trader was trading or already exposed to. Market makers prefer to profit from the spread, bidding below some predetermined price, based upon the cost basis of the market maker's inventory, while asking above that same predetermined cost basis. Traders profit from taking exposure to a security's direction or lack thereof in the case of some options traders. Because of electronic trading, liquidity rebates offered by exchanges not only to contractually obligated official market makers but also to any trader who posts a limit order that another trader hits, and algorithms that become better by the day, market making HFTs have supplanted the traditional market maker, and there are many HFTs where there previously were few official market makers. This speed and diversification of risk across many many algorithmically market making HFTs have kept spreads to the minimum on large equities and have reduced the same for the smallest equities on major exchanges. Orders and quotes are essentially identical. Both are double sided auction markets with impermenant bids and asks. The difference lies in that non-market makers, specialists, etc. orders are not shown to the rest of the market, providing an informational advantage to MMs and an informational disadvantage to the trader. Before electronic trading, this construct was of no consequence since trader orders were infrequent. With the prevalence of HFTs, the informational disadvantage has become more costly, so order driven markets now prevail with much lower spreads and accelerated volumes even though market share for the major exchanges has dropped rapidly and hyperaccelerated number of trades even though the size of individual trades have fallen. The worst aspect of the quote driven market was that traders could not directly trade with each other, so all trades had to go between a market maker, specialist, etc. While this may seem to have increased cost to a trader who could only trade with another trader by being arbitraged by a MM et al, paying more than what another trader was willing to sell, these costs were dwarfed by the potential absence of those market makers. Without a bid or ask at any given time, there could be no trade, so the costs were momentarily infinite. In essence, a quote driven market protects market makers from the competition of traders. While necessary in the days where paper receipts were carted from brokerage to brokerage, and the trader did not dedicate itself to round the clock trading, it has no place in a computerized market. It is more costly to the trader to use such a market, explaining quote driven markets' rapid exit.", "title": "" }, { "docid": "39265", "text": "In addition to the higher risk as pointed out by @JamesRoth, you also need to consider that there are regulations against 'naked shorting' so you generally need to either own the security, or have someone that is willing to 'loan' the security to you in order to sell short. If you own a stock you are shorting, the IRS could view the transaction as a Sell followed by a buy taking place in a less than 30 day period and you could be subject to wash-sale rules. This added complexity (most often the finding of someone to loan you the security you are shorting) is another reason such trades are considered more advanced. You should also be aware that there are currently a number of proposals to re-instate the 'uptick rule' or some circuit-breaker variant. Designed to prevent short-sellers from driving down the price of a stock (and conducting 'bear raids etc) the first requires that a stock trade at the same or higher price as prior trades before you can submit a short. In the latter shorting would be prohibited after a stock price had fallen a given percentage in a given amount of time. In either case, should such a rule be (re)established then you could face limitations attempting to execute a short which you would not need to worry about doing simple buys or sells. As to vehicles that would do this kind of thing (if you are convinced we are in a bear market and willing to take the risk) there are a number of ETF's classified as 'Inverse Exchange Traded Funds (ETF's) for a variety of markets that via various means seek to deliver a return similar to that of 'shorting the market' in question. One such example for a common broad market is ticker SH the ProShares Short S&P500 ETF, which seeks to deliver a return that is the inverse of the S&P500 (and as would be predicted based on the roughly +15% performance of the S&P500 over the last 12 months, SH is down roughly -15% over the same period). The Wikipedia article on inverse ETF's lists a number of other such funds covering various markets. I think it should be noted that using such a vehicle is a pretty 'aggressive bet' to take in reaction to the belief that a bear market is imminent. A more conservative approach would be to simply take money out of the market and place it in something like CD's or Treasury instruments. In that case, you preserve your capital, regardless of what happens in the market. Using an inverse ETF OTOH means that if the market went bull instead of bear, you would lose money instead of merely holding your position.", "title": "" }, { "docid": "23443", "text": "As a beginner to cryptocurrencies, I would recommend that you sign up for an account at gemini.com. Once you get verified - and understand, that getting verified will take multiple weeks, unfortunately, considering the large amount of traffic that these web apps still have to scale for - you will be able to make daily deposits of $500 to buy either bitcoin (BTC) or ethereum (ETH). Any other currencies (altcoins, usually built on another network or entirely separate networks) will require you to sign up for an altcoin exchange like Kraken or Poloniex. Speaking of which, another user that commented on this post mentioned Kraken, but the issue with Kraken is that it only allows you to buy currencies using other currency, which is why I recommend gemini (you could even use coinbase, but coinbase is EXTREMELY popular and it takes forever to get verified). After purchasing crypto, you can transfer to other accounts on other exchanges to speculate on altcoin. Please be secure when using these exchanges. Consider also using a wallet (I personally recommend exodus.io), as many exchanges suffer from occasional attacks. As for /u/beat_tapes questioning your motives, I totally agree with that sentiment, as no one REALLY knows what's going to happen tomorrow, which is why I implore you to evaluate your financial situation and only speculate with what you're entirely comfortable with losing. You're entering casino doors, and yeah, I'm a personal believer that at this casino you'll win big, but it's still a gamble. Just keep that in mind.", "title": "" }, { "docid": "505865", "text": "Okay. They're faster than most other computers. They either have a dedicated fiber line or are physically closer. But anyways, they flood the NYSE with tons of orders to slow it down. So they see another broker's order in the line up and delete the bogus orders. They can then make the purchase faster than the other guy. The other guy now has to pay a higher strike price than he initially thought the bid would be. So let's say Apple's quote is 1.00 They send one order for apple One for IBM One for Yahoo One for NBC Comcast They see another guy wants Apple. So they cancel the orders for IBM, Yahoo and NBC Comcast and leave the Apple one to complete. The Apple one goes through and then they automatically resell it to the guy looking to buy Apple at a price of 1.0001 TLDR They flood a bunch of orders at a bunch of different prices/quantities. They cancel before it goes through unless they see someone else wants it. If that person wants it they don't cancel. edit: I don't even know if all or any of those stocks are listed on the NYSE. In today's world it doesn't make a difference anymore. However, replace NYSE with any exchange and the stock with any ticker symbol. edit 2: They could also manipulate cross listing. Listing the same stock on two different exchanges. Those prices are mostly uniform but of course higher volume on one could mean a higher price on one before they stabilize. So if you can move fast you can buy the stock at the lower price and sell it on the exchange with the higher price.", "title": "" }, { "docid": "67006", "text": "For stocks, I would not see these as profiting at the expense of another individual. When you purchase/trade stocks, you are exchanging items of equal market value at the time of the trade. Both parties are getting a fair exchange when the transaction happens. If you buy a house, the seller has not profited at your expense. You have exchanged goods at market prices. If your house plummets in value and you lose $100k, it is not the sellers fault that you made the decision to purchase. The price was fair when you exchanged the goods. Future prices are speculative, so both parties must perform due diligence to make sure the exchange aligns with their interests. Obviously, this is barring any sort of dishonesty or insider information on the part of either buyer or seller.", "title": "" }, { "docid": "435883", "text": "I am not a tax professional, only an investment professional, so please take the following with a grain of salt and simply as informational guidance, not a personal recommendation or solicitation to buy/sell any security or as personal tax or investment advice. As Ross mentioned, you need to consult a tax advisor for a final answer concerning your friend's personal circumstances. In my experience advising hundreds of clients (and working directly with their tax advisors) the cost basis is used to calculate tax gain or loss on ordinary investments in the US. It appears to me that the Edward Jones description is correct. This has also been the case for me personally in the US with a variety of securities--stocks, options, futures, bonds, mutual funds, and exchange traded funds. From the IRS: https://www.irs.gov/uac/about-form-1099b Form 1099-B, Proceeds From Broker and Barter Exchange Transactions A broker or barter exchange must file this form for each person: Edward Jones should be able to produce a 1099b documenting the gains/losses of any investments. If the 1099b document is confusing, they might have a gain/loss report that more clearly delineates proceeds, capital returns, dividends, and other items related to the purchase and sale of securities.", "title": "" } ]
265	Clathrin stabilizes the spindle fiber apparatus during mitosis.	[ { "docid": "2033917", "text": "Clathrin has an established function in the generation of vesicles that transfer membrane and proteins around the cell. The formation of clathrin-coated vesicles occurs continuously in non-dividing cells, but is shut down during mitosis, when clathrin concentrates at the spindle apparatus. Here, we show that clathrin stabilizes fibres of the mitotic spindle to aid congression of chromosomes. Clathrin bound to the spindle directly by the amino-terminal domain of clathrin heavy chain. Depletion of clathrin heavy chain using RNA interference prolonged mitosis; kinetochore fibres were destabilized, leading to defective congression of chromosomes to the metaphase plate and persistent activation of the spindle checkpoint. Normal mitosis was rescued by clathrin triskelia but not the N-terminal domain of clathrin heavy chain, indicating that stabilization of kinetochore fibres was dependent on the unique structure of clathrin. The importance of clathrin for normal mitosis may be relevant to understanding human cancers that involve gene fusions of clathrin heavy chain.", "title": "Clathrin is required for the function of the mitotic spindle" } ]	[ { "docid": "14205246", "text": "The spindle apparatus is a microtubule (MT)-based machinery that attaches to and segregates the chromosomes during mitosis and meiosis. Self-organization of the spindle around chromatin involves the assembly of MTs, their attachment to the chromosomes, and their organization into a bipolar array. One regulator of spindle self-organization is RanGTP. RanGTP is generated at chromatin and activates a set of soluble, Ran-regulated spindle factors such as TPX2, NuMA, and NuSAP . How the spindle factors direct and attach MTs to the chromosomes are key open questions. Nucleolar and Spindle-Associated Protein (NuSAP) was recently identified as an essential MT-stabilizing and bundling protein that is enriched at the central part of the spindle . Here, we show by biochemical reconstitution that NuSAP efficiently adsorbs to isolated chromatin and DNA and that it can directly produce and retain high concentrations of MTs in the immediate vicinity of chromatin or DNA. Moreover, our data reveal that NuSAP-chromatin interaction is subject to Ran regulation and can be suppressed by Importin alpha (Impalpha) and Imp7. We propose that the presence of MT binding agents such as NuSAP, which can be directly immobilized on chromatin, are critical for targeting MT production to vertebrate chromosomes during spindle self-organization.", "title": "A Role for NuSAP in Linking Microtubules to Mitotic Chromosomes" }, { "docid": "38127792", "text": "In mitosis the cell assembles the bipolar spindle, a microtubule (MT)-based apparatus that segregates the duplicated chromosomes into two daughter cells. Most animal cells enter mitosis with duplicated centrosomes that provide an active source of dynamic MTs. However, it is now established that spindle assembly relies on the nucleation of acentrosomal MTs occurring around the chromosomes after nuclear envelope breakdown, and on pre-existing microtubules. Where chromosome-dependent MT nucleation occurs, when MT amplification takes place and how the two pathways function are still key questions that generate some controversies. We reconcile the data and present an integrated model accounting for acentrosomal microtubule assembly in the dividing cell.", "title": "Acentrosomal Microtubule Assembly in Mitosis: The Where, When, and How." }, { "docid": "17805221", "text": "Sport fishermen keep tension on their lines to prevent hooked fish from releasing. A molecular version of this angler's trick, operating at kinetochores, ensures accuracy during mitosis: the mitotic spindle attaches randomly to chromosomes and then correctly bioriented attachments are stabilized due to the tension exerted on them by opposing microtubules. Incorrect attachments, which lack tension, are unstable and release quickly, allowing another chance for biorientation. Stabilization of molecular interactions by tension also occurs in other physiological contexts, such as cell adhesion, motility, hemostasis, and tissue morphogenesis. Here, we review models for the stabilization of kinetochore attachments with an eye toward emerging models for other force-activated systems. Although attention in the mitosis field has focused mainly on one kinase-based mechanism, multiple mechanisms may act together to stabilize properly bioriented kinetochores and some principles governing other tension-sensitive systems may also apply to kinetochores.", "title": "Catch and release: how do kinetochores hook the right microtubules during mitosis?" }, { "docid": "1684489", "text": "BACKGROUND Production of the GTP-bound form of the Ran GTPase (RanGTP) around chromosomes induces spindle assembly by activating nuclear localization signal (NLS)-containing proteins. Several NLS proteins have been identified as spindle assembly factors, but the complexity of the process led us to search for additional proteins with distinct roles in spindle assembly. RESULTS We identify a chromatin-remodeling ATPase, CHD4, as a RanGTP-dependent microtubule (MT)-associated protein (MAP). MT binding occurs via the region containing an NLS and chromatin-binding domains. In Xenopus egg extracts and cultured cells, CHD4 largely dissociates from mitotic chromosomes and partially localizes to the spindle. Immunodepletion of CHD4 from egg extracts significantly reduces the quantity of MTs produced around chromatin and prevents spindle assembly. CHD4 RNAi in both HeLa and Drosophila S2 cells induces defects in spindle assembly and chromosome alignment in early mitosis, leading to chromosome missegregation. Further analysis in egg extracts and in HeLa cells reveals that CHD4 is a RanGTP-dependent MT stabilizer. Moreover, the CHD4-containing NuRD complex promotes organization of MTs into bipolar spindles in egg extracts. Importantly, this function of CHD4 is independent of chromatin remodeling. CONCLUSIONS Our results uncover a new role for CHD4 as a MAP required for MT stabilization and involved in generating spindle bipolarity.", "title": "CHD4 Is a RanGTP-Dependent MAP that Stabilizes Microtubules and Regulates Bipolar Spindle Formation" }, { "docid": "600808", "text": "Cyclin A is a stable protein in S and G2 phases, but is destabilized when cells enter mitosis and is almost completely degraded before the metaphase to anaphase transition. Microinjection of antibodies against subunits of the anaphase-promoting complex/cyclosome (APC/C) or against human Cdc20 (fizzy) arrested cells at metaphase and stabilized both cyclins A and B1. Cyclin A was efficiently polyubiquitylated by Cdc20 or Cdh1-activated APC/C in vitro, but in contrast to cyclin B1, the proteolysis of cyclin A was not delayed by the spindle assembly checkpoint. The degradation of cyclin B1 was accelerated by inhibition of the spindle assembly checkpoint. These data suggest that the APC/C is activated as cells enter mitosis and immediately targets cyclin A for degradation, whereas the spindle assembly checkpoint delays the degradation of cyclin B1 until the metaphase to anaphase transition. The “destruction box” (D-box) of cyclin A is 10–20 residues longer than that of cyclin B. Overexpression of wild-type cyclin A delayed the metaphase to anaphase transition, whereas expression of cyclin A mutants lacking a D-box arrested cells in anaphase.", "title": "Anaphase-Promoting Complex/Cyclosome–Dependent Proteolysis of Human Cyclin a Starts at the Beginning of Mitosis and Is Not Subject to the Spindle Assembly Checkpoint" }, { "docid": "11020675", "text": "Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. However, the mechanism underlying this polyploidization remains totally unknown. It has been postulated that polyploidization is due to a skipping of mitosis after each round of DNA replication. We carried out immunohistochemical studies on mouse bone marrow megakaryocytes during thrombopoietin- induced polyploidization and found that during this process megakaryocytes indeed enter mitosis and progress through normal prophase, prometaphase, metaphase, and up to anaphase A, but not to anaphase B, telophase, or cytokinesis. It was clearly observed that multiple spindle poles were formed as the polyploid megakaryocytes entered mitosis; the nuclear membrane broke down during prophase; the sister chromatids were aligned on a multifaced plate, and the centrosomes were symmetrically located on either side of each face of the plate at metaphase; and a set of sister chromatids moved into the multiple centrosomes during anaphase A. We further noted that the pair of spindle poles in anaphase were located in close proximity to each other, probably because of the lack of outward movement of spindle poles during anaphase B. Thus, the reassembling nuclear envelope may enclose all the sister chromatids in a single nucleus at anaphase and then skip telophase and cytokinesis. These observations clearly indicate that polyploidization of megakaryocytes is not simply due to a skipping of mitosis, and that the megakaryocytes must have a unique regulatory mechanism in anaphase, e.g., factors regulating anaphase such as microtubule motor proteins might be involved in this polyploidization process.", "title": "Thrombopoietin-induced Polyploidization of Bone Marrow Megakaryocytes Is Due to a Unique Regulatory Mechanism in Late Mitosis " }, { "docid": "4398832", "text": "The most conspicuous event in the cell cycle is the alignment of chromosomes in metaphase. Chromosome alignment fosters faithful segregation through the formation of bi-oriented attachments of kinetochores to spindle microtubules. Notably, numerous kinetochore-microtubule (k-MT) attachment errors are present in early mitosis (prometaphase), and the persistence of those errors is the leading cause of chromosome mis-segregation in aneuploid human tumour cells that continually mis-segregate whole chromosomes and display chromosomal instability. How robust error correction is achieved in prometaphase to ensure error-free mitosis remains unknown. Here we show that k-MT attachments in prometaphase cells are considerably less stable than in metaphase cells. The switch to more stable k-MT attachments in metaphase requires the proteasome-dependent destruction of cyclin A in prometaphase. Persistent cyclin A expression prevents k-MT stabilization even in cells with aligned chromosomes. By contrast, k-MTs are prematurely stabilized in cyclin-A-deficient cells. Consequently, cells lacking cyclin A display higher rates of chromosome mis-segregation. Thus, the stability of k-MT attachments increases decisively in a coordinated fashion among all chromosomes as cells transit from prometaphase to metaphase. Cyclin A creates a cellular environment that promotes microtubule detachment from kinetochores in prometaphase to ensure efficient error correction and faithful chromosome segregation.", "title": "Cyclin A Regulates Kinetochore-Microtubules to Promote Faithful Chromosome Segregation" }, { "docid": "14119470", "text": "Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase activating protein, RanGAP1, and by a guanine nucleotide exchange factor, RCC1. Ran also interacts with a guanine nucleotide dissociation inhibitor, RanBP1. RanBP1 has a high affinity for GTP-bound Ran, and it acts as a cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.", "title": "The Ran GTPase regulates mitotic spindle assembly" }, { "docid": "13953762", "text": "The Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase bridges (UFBs) in mitosis alongside a complex of DNA repair proteins, including the Bloom's syndrome protein (BLM). However, very little is known about the function of PICH or how it is recruited to UFBs. Using a combination of microfluidics, fluorescence microscopy, and optical tweezers, we have defined the properties of PICH in an in vitro model of an anaphase bridge. We show that PICH binds with a remarkably high affinity to duplex DNA, resulting in ATP-dependent protein translocation and extension of the DNA. Most strikingly, the affinity of PICH for binding DNA increases with tension-induced DNA stretching, which mimics the effect of the mitotic spindle on a UFB. PICH binding also appears to diminish force-induced DNA melting. We propose a model in which PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids.", "title": "PICH: a DNA translocase specially adapted for processing anaphase bridge DNA." }, { "docid": "24558930", "text": "Although assembly of acentrosomal meiotic spindles has been extensively studied, little is known about the segregation of chromosomes on these spindles. Here, we show in Caenorhabditis elegans oocytes that the kinetochore protein, KNL-1, directs assembly of meiotic kinetochores that orient chromosomes. However, in contrast to mitosis, chromosome separation during meiotic anaphase is kinetochore-independent. Before anaphase, meiotic kinetochores and spindle poles disassemble along with the microtubules on the poleward side of chromosomes. During anaphase, microtubules then form between the separating chromosomes. Functional analysis implicated a set of proteins that localize to a ring-shaped domain between kinetochores during pre-anaphase spindle assembly and anaphase separation. These proteins are localized by the chromosomal passenger complex, which regulates the loss of meiotic chromosome cohesion. Thus, meiotic segregation in C. elegans is a two-stage process, where kinetochores orient chromosomes, but are then dispensable for their separation. We suggest that separation is controlled by a meiosis-specific chromosomal domain to coordinate cohesin removal and chromosome segregation.", "title": "A kinetochore-independent mechanism drives anaphase chromosome separation during acentrosomal meiosis" }, { "docid": "6472746", "text": "Chromosome segregation during cell division depends on stable attachment of kinetochores to spindle microtubules. Mitotic spindle formation and kinetochore-microtubule (K-MT) capture typically occur within minutes of nuclear envelope breakdown. In contrast, during meiosis I in mouse oocytes, formation of the acentrosomal bipolar spindle takes 3-4 h, and stabilization of K-MT attachments is delayed an additional 3-4 h. The mechanism responsible for this delay, which likely prevents stabilization of erroneous attachments during spindle formation, is unknown. Here we show that during meiosis I, attachments are regulated by CDK1 activity, which gradually increases through prometaphase and metaphase I. Partial reduction of CDK1 activity delayed formation of stable attachments, whereas a premature increase in CDK1 activity led to precocious formation of stable attachments and eventually lagging chromosomes at anaphase I. These results indicate that the slow increase in CDK1 activity in meiosis I acts as a timing mechanism to allow stable K-MT attachments only after bipolar spindle formation, thus preventing attachment errors.", "title": "Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I" }, { "docid": "7681810", "text": "Mitotic spindle assembly is mediated by two processes: a centrosomal and a chromosomal pathway. RanGTP regulates the latter process by releasing microtubule-associated proteins from inhibitory complexes. NuSAP, a microtubule- and DNA-binding protein, is a target of RanGTP and promotes the formation of microtubules near chromosomes. However, the contribution of NuSAP to cell proliferation in vivo is unknown. Here, we demonstrate that the expression of NuSAP highly correlates with cell proliferation during embryogenesis and adult life, making it a reliable marker of proliferating cells. Additionally, we show that NuSAP deficiency in mice leads to early embryonic lethality. Spindle assembly in NuSAP-deficient cells is highly inefficient and chromosomes remain dispersed in the mitotic cytoplasm. As a result of sustained spindle checkpoint activity, the cells are unable to progress through mitosis, eventually leading to caspase activation and apoptotic cell death. Together, our findings demonstrate that NuSAP is essential for proliferation of embryonic cells and, simultaneously, they underscore the importance of chromatin-induced spindle assembly.", "title": "NuSAP is essential for chromatin-induced spindle formation during early embryogenesis." }, { "docid": "11041152", "text": "Molecular motors play critical roles in the formation of mitotic spindles, either through controlling the stability of individual microtubules, or by crosslinking and sliding microtubule arrays. Kinesin-8 motors are best known for their regulatory roles in controlling microtubule dynamics. They contain microtubule-destabilizing activities, and restrict spindle length in a wide variety of cell types and organisms. Here, we report an antiparallel microtubule-sliding activity of the budding yeast kinesin-8, Kip3. The in vivo importance of this sliding activity was established through the identification of complementary Kip3 mutants that separate the sliding activity and microtubule-destabilizing activity. In conjunction with Cin8, a kinesin-5 family member, the sliding activity of Kip3 promotes bipolar spindle assembly and the maintenance of genome stability. We propose a slide-disassemble model where the sliding and destabilizing activity of Kip3 balance during pre-anaphase. This facilitates normal spindle assembly. However, the destabilizing activity of Kip3 dominates in late anaphase, inhibiting spindle elongation and ultimately promoting spindle disassembly.", "title": "Microtubule sliding activity of a kinesin-8 promotes spindle assembly and spindle length control" }, { "docid": "11674596", "text": "A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible \"wait anaphase\" signal to the vicinity of the spindle.", "title": "Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator" }, { "docid": "493346", "text": "How sister kinetochores attach to microtubules from opposite spindle poles during mitosis (bi-orientation) remains poorly understood. In yeast, the ortholog of the Aurora B-INCENP protein kinase complex (Ipl1-Sli15) may have a role in this crucial process, because it is necessary to prevent attachment of sister kinetochores to microtubules from the same spindle pole. We investigated IPL1 function in cells that cannot replicate their chromosomes but nevertheless duplicate their spindle pole bodies (SPBs). Kinetochores detach from old SPBs and reattach to old and new SPBs with equal frequency in IPL1+ cells, but remain attached to old SPBs in ipl1 mutants. This raises the possibility that Ipl1-Sli15 facilitates bi-orientation by promoting turnover of kinetochore-SPB connections until traction of sister kinetochores toward opposite spindle poles creates tension in the surrounding chromatin.", "title": "Evidence that the Ipl1-Sli15 (Aurora Kinase-INCENP) Complex Promotes Chromosome Bi-orientation by Altering Kinetochore-Spindle Pole Connections" }, { "docid": "7114092", "text": "Megakaryocyte (MK) is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered to be an incomplete mitosis aborted in anaphase. Here, we used time-lapse confocal video microscopy to visualize the endomitotic process of primary human megakaryocytes. Our results show that the switch from mitosis to endomitosis corresponds to a late failure of cytokinesis accompanied by a backward movement of the 2 daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal because accumulation of nonmuscle myosin IIA was lacking. In addition, a defect in cell elongation was observed in dipolar endomitotic MKs during telophase. RhoA and F-actin were partially concentrated at the site of furrowing. Inhibition of the Rho/Rock pathway caused the disappearance of F-actin at midzone and increased MK ploidy level. This inhibition was associated with a more pronounced defect in furrow formation as well as in spindle elongation. Our results suggest that the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation.", "title": "From bloodjournal.hematologylibrary.org at PENN STATE UNIVERSITY on February 23, 2013. For personal use only." }, { "docid": "4421746", "text": "Polyploidy, increased sets of chromosomes, occurs during development, cellular stress, disease and evolution. Despite its prevalence, little is known about the physiological alterations that accompany polyploidy. We previously described ‘ploidy-specific lethality’, where a gene deletion that is not lethal in haploid or diploid budding yeast causes lethality in triploids or tetraploids. Here we report a genome-wide screen to identify ploidy-specific lethal functions. Only 39 out of 3,740 mutations screened exhibited ploidy-specific lethality. Almost all of these mutations affect genomic stability by impairing homologous recombination, sister chromatid cohesion, or mitotic spindle function. We uncovered defects in wild-type tetraploids predicted by the screen, and identified mechanisms by which tetraploidization affects genomic stability. We show that tetraploids have a high incidence of syntelic/monopolar kinetochore attachments to the spindle pole. We suggest that this defect can be explained by mismatches in the ability to scale the size of the spindle pole body, spindle and kinetochores. Thus, geometric constraints may have profound effects on genome stability; the phenomenon described here may be relevant in a variety of biological contexts, including disease states such as cancer.", "title": "Genome-wide genetic analysis of polyploidy in yeast" }, { "docid": "2991954", "text": "Production of Ran-guanosine triphosphate (GTP) around chromosomes induces local nucleation and plus end stabilization of microtubules (MTs). The nuclear protein TPX2 is required for RanGTP-dependent MT nucleation. To find the MT stabilizer, we affinity purify nuclear localization signal (NLS)-containing proteins from Xenopus laevis egg extracts. This NLS protein fraction contains the MT stabilization activity. After further purification, we used mass spectrometry to identify proteins in active fractions, including cyclin-dependent kinase 11 (Cdk11). Cdk11 localizes on spindle poles and MTs in Xenopus culture cells and egg extracts. Recombinant Cdk11 demonstrates RanGTP-dependent MT stabilization activity, whereas a kinase-dead mutant does not. Inactivation of Cdk11 in egg extracts blocks RanGTP-dependent MT stabilization and dramatically decreases the spindle assembly rate. Simultaneous depletion of TPX2 completely inhibits centrosome-dependent spindle assembly. Our results indicate that Cdk11 is responsible for RanGTP-dependent MT stabilization around chromosomes and that this local stabilization is essential for normal rates of spindle assembly and spindle function.", "title": "Cdk11 is a RanGTP-dependent microtubule stabilization factor that regulates spindle assembly rate" }, { "docid": "24555417", "text": "In many species, oocyte meiosis is carried out in the absence of centrioles. As a result, microtubule organization, spindle assembly, and chromosome segregation proceed by unique mechanisms. Here, we report insights into the principles underlying this specialized form of cell division, through studies of C. elegans KLP-15 and KLP-16, two highly homologous members of the kinesin-14 family of minus-end-directed kinesins. These proteins localize to the acentriolar oocyte spindle and promote microtubule bundling during spindle assembly; following KLP-15/16 depletion, microtubule bundles form but then collapse into a disorganized array. Surprisingly, despite this defect we found that during anaphase, microtubules are able to reorganize into a bundled array that facilitates chromosome segregation. This phenotype therefore enabled us to identify factors promoting microtubule organization during anaphase, whose contributions are normally undetectable in wild-type worms; we found that SPD-1 (PRC1) bundles microtubules and KLP-18 (kinesin-12) likely sorts those bundles into a functional orientation capable of mediating chromosome segregation. Therefore, our studies have revealed an interplay between distinct mechanisms that together promote spindle formation and chromosome segregation in the absence of structural cues such as centrioles.", "title": "Interplay between microtubule bundling and sorting factors ensures acentriolar spindle stability during C. elegans oocyte meiosis" }, { "docid": "42035464", "text": "Microtubule nucleation is the best known function of centrosomes. Centrosomal microtubule nucleation is mediated primarily by gamma tubulin ring complexes (gamma TuRCs). However, little is known about the molecules that anchor these complexes to centrosomes. In this study, we show that the centrosomal coiled-coil protein pericentrin anchors gamma TuRCs at spindle poles through an interaction with gamma tubulin complex proteins 2 and 3 (GCP2/3). Pericentrin silencing by small interfering RNAs in somatic cells disrupted gamma tubulin localization and spindle organization in mitosis but had no effect on gamma tubulin localization or microtubule organization in interphase cells. Similarly, overexpression of the GCP2/3 binding domain of pericentrin disrupted the endogenous pericentrin-gamma TuRC interaction and perturbed astral microtubules and spindle bipolarity. When added to Xenopus mitotic extracts, this domain uncoupled gamma TuRCs from centrosomes, inhibited microtubule aster assembly, and induced rapid disassembly of preassembled asters. All phenotypes were significantly reduced in a pericentrin mutant with diminished GCP2/3 binding and were specific for mitotic centrosomal asters as we observed little effect on interphase asters or on asters assembled by the Ran-mediated centrosome-independent pathway. Additionally, pericentrin silencing or overexpression induced G2/antephase arrest followed by apoptosis in many but not all cell types. We conclude that pericentrin anchoring of gamma tubulin complexes at centrosomes in mitotic cells is required for proper spindle organization and that loss of this anchoring mechanism elicits a checkpoint response that prevents mitotic entry and triggers apoptotic cell death.", "title": "Mitosis-specific anchoring of gamma tubulin complexes by pericentrin controls spindle organization and mitotic entry." }, { "docid": "20054396", "text": "In animal cells, most microtubules are nucleated at centrosomes. At the onset of mitosis, centrosomes undergo a structural reorganization, termed maturation, which leads to increased microtubule nucleation activity. Centrosome maturation is regulated by several kinases, including Polo-like kinase 1 (Plk1). Here, we identify a centrosomal Plk1 substrate, termed Nlp (ninein-like protein), whose properties suggest an important role in microtubule organization. Nlp interacts with two components of the gamma-tubulin ring complex and stimulates microtubule nucleation. Plk1 phosphorylates Nlp and disrupts both its centrosome association and its gamma-tubulin interaction. Overexpression of an Nlp mutant lacking Plk1 phosphorylation sites severely disturbs mitotic spindle formation. We propose that Nlp plays an important role in microtubule organization during interphase, and that the activation of Plk1 at the onset of mitosis triggers the displacement of Nlp from the centrosome, allowing the establishment of a mitotic scaffold with enhanced microtubule nucleation activity.", "title": "Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation." }, { "docid": "29183629", "text": "Using laser microsurgery and cell fusion we have explored how additional centrosomes and/or chromosomes influence the duration of mitosis in human cells. We found that doubling the chromosome number added approximately 10 min to a 20 min division, whereas doubling the number of centrosomes added approximately 30 min more. Extra centrosomes and/or chromosomes prolong mitosis by delaying satisfaction of the spindle assembly checkpoint. Thus mitosis can be prolonged by non-genetic means and extra chromosomes and centrosomes probably contribute to the elevated mitotic index seen in many tumours.", "title": "Extra centrosomes and/or chromosomes prolong mitosis in human cells" }, { "docid": "7666498", "text": "Mitosis is controlled by multiple kinases that drive cell cycle progression and prevent chromosome mis-segregation. Aurora kinase B interacts with survivin, borealin and incenp to form the chromosomal passenger complex (CPC), which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis. Whereas genetic ablation of survivin, borealin or incenp results in early lethality at the morula stage, we show here that aurora B is dispensable for CPC function during early cell divisions and aurora B-null embryos are normally implanted. This is due to a crucial function of aurora C during these early embryonic cycles. Expression of aurora C decreases during late blastocyst stages resulting in post-implantation defects in aurora B-null embryos. These defects correlate with abundant prometaphase figures and apoptotic cell death of the aurora B-deficient inner cell mass. Conditional deletion of aurora B in somatic cells that do not express aurora C results in chromosomal misalignment and lack of chromosome segregation. Re-expression of wild-type, but not kinase-dead, aurora C rescues this defect, suggesting functional overlap between these two kinases. Finally, aurora B-null cells partially arrest in the presence of nocodazole, suggesting that this kinase is not essential for the spindle assembly checkpoint.", "title": "Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development." }, { "docid": "4343437", "text": "Drosophila neuroblasts and epithelial cells in the procephalic neurogenic region divide perpendicular to the surface, and segregate the proteins Numb and Prospero into the basal daughter cell. We demonstrate here that orientation of the mitotic spindle and correct localization of Numb and Prospero in these cells require the inscuteable gene. Moreover, ectopic expression of inscuteable in other epithelial cells leads to spindle reorientation. The Inscuteable protein localizes to the apical cell cortex before mitosis, suggesting that Inscuteable functions in establishing polarity for asymmetric cell division.", "title": "Role of inscuteable in orienting asymmetric cell divisions in Drosophila" }, { "docid": "13583615", "text": "During meiosis I, kinetochores of sister chromatids are juxtaposed or fused and mono-orient, while homologous chromosomes that are paired by chiasmata (bivalents) have to biorient. In the absence of chiasmata, biorientation of sister chromatids (univalents), which carries a risk of aneuploidy, has been occasionally detected in several species, including humans. We show in fission yeast that biorientation of fused sister kinetochores predominates during early prometaphase I. Without chiasmata, this undesirable biorientation of univalents persists and eventually evades the spindle assembly checkpoint, provoking abnormal anaphase. When univalents are connected by chiasmata or by an artificial tether, this erroneous attachment is converted to monopolar attachment and stabilized. This stabilization is apparently achieved by a chromosome configuration that brings kinetochores to the outer edge of the bivalent, while bringing Aurora B, a destabilizer of kinetochore-microtubule attachment, inward. Our results elucidate how chiasmata favor biorientation of bivalents over that of univalents at meiosis I.", "title": "Repositioning of aurora B promoted by chiasmata ensures sister chromatid mono-orientation in meiosis I." }, { "docid": "7223604", "text": "To study the effector function of the ADP- ribosylation factor (ARF) 6 GTP-binding protein, we transfected HeLa cells with wild-type, epitope-tagged ARF6. Previously shown to indirectly activate the ARF1 GTPase, aluminum fluoride (AIF) treatment of ARF6-transfected cells resulted in a redistribution of both ARF6 and actin to discrete sites on the plasma membrane, which became increasingly protrusive over time. The effects of AIF were reversible, specific to cells transfected with wild-type ARF6, and resembled the cellular protrusions observed in cells expressing the GTPase defective mutant of ARF6. Importantly, the protrusions observed in cells transfected with ARF6 were distinct from the enhanced stress fibers and membrane ruffles observed in cells transfected with RhoA and Rac1, respectively. In cells forming protrusions, there was an apparent stimulation of macropinocytosis and membrane recycling within the protrusive structures. In contrast, no block in transferrin uptake or alteration of the distribution of clathrin AP-2 complexes was detected in these cells. The AIF-induced, ARF6- dependent formation of protrusive structures was blocked by cytochalasin D and inhibitors of the lipoxygenase pathway. These observations support a novel role for the ARF6 GTPase in modeling the plasma membrane and underlying cytoskeleton.", "title": "Aluminum fluoride stimulates surface protrusions in cells overexpressing the ARF6 GTPase" }, { "docid": "39758684", "text": "To reach the biological alterations that characterize cancer, the genome of tumor cells must acquire increased mutability resulting from a malfunction of a network of genome stability systems, e.g., cell cycle arrest, DNA repair, and high accuracy of DNA synthesis during DNA replication. Numeric chromosomal imbalance, referred to as aneuploidy, is the most prevalent genetic changes recorded among many types of solid tumors. We report here that ectopic expression in cells of DNA polymerase beta, an error-prone enzyme frequently over-regulated in human tumors, induces aneuploidy, an abnormal localization of the centrosome-associated gamma-tubulin protein during mitosis, a deficient mitotic checkpoint, and promotes tumorigenesis in nude immunodeficient mice. Thus, we find that alteration of polymerase beta expression appears to induce major genetic changes associated with a malignant phenotype.", "title": "Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis." }, { "docid": "15926408", "text": "A major challenge each human cell-division cycle is to ensure that DNA replication origins do not initiate more than once, a phenomenon known as re-replication. Acute deregulation of replication control ultimately causes extensive DNA damage, cell-cycle checkpoint activation and cell death whereas moderate deregulation promotes genome instability and tumorigenesis. In the absence of detectable increases in cellular DNA content however, it has been difficult to directly demonstrate re-replication or to determine if the ability to re-replicate is restricted to a particular cell-cycle phase. Using an adaptation of DNA fiber spreading we report the direct detection of re-replication on single DNA molecules from human chromosomes. Using this method we demonstrate substantial re-replication within 1 h of S phase entry in cells overproducing the replication factor, Cdt1. Moreover, a comparison of the HeLa cancer cell line to untransformed fibroblasts suggests that HeLa cells produce replication signals consistent with low-level re-replication in otherwise unperturbed cell cycles. Re-replication after depletion of the Cdt1 inhibitor, geminin, in an untransformed fibroblast cell line is undetectable by standard assays but readily quantifiable by DNA fiber spreading analysis. Direct evaluation of re-replicated DNA molecules will promote increased understanding of events that promote or perturb genome stability.", "title": "Analysis of re-replication from deregulated origin licensing by DNA fiber spreading" }, { "docid": "10704438", "text": "Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed.", "title": "The DNA damage response during mitosis." }, { "docid": "15960670", "text": "The centromere is a chromatin region that serves as the spindle attachment point and directs accurate inheritance of eukaryotic chromosomes during cell divisions. However, the mechanism by which the centromere assembles and stabilizes at a specific genomic region is not clear. The de novo formation of a human/mammalian artificial chromosome (HAC/MAC) with a functional centromere assembly requires the presence of alpha-satellite DNA containing binding motifs for the centromeric CENP-B protein. We demonstrate here that de novo centromere assembly on HAC/MAC is dependent on CENP-B. In contrast, centromere formation is suppressed in cells expressing CENP-B when alpha-satellite DNA was integrated into a chromosomal site. Remarkably, on those integration sites CENP-B enhances histone H3-K9 trimethylation and DNA methylation, thereby stimulating heterochromatin formation. Thus, we propose that CENP-B plays a dual role in centromere formation, ensuring de novo formation on DNA lacking a functional centromere but preventing the formation of excess centromeres on chromosomes.", "title": "CENP-B Controls Centromere Formation Depending on the Chromatin Context" } ]
6680	Merchant dispute with airline over changed itinerary	[ { "docid": "472524", "text": "\"Are you on Twitter? If so, the first thing I'd do is tweet this question to @Orbitz and/or @AmericanAir (AA). I'll edit it to be a bit nicer english-wise. Tweeting (or Facebooking or Instgramming or ...) is one of the most effective ways to get customer service in 'edge' cases. Explain your case in a nice, tight narrative that has the pertinent facts, why you should get an exception. Social media tends to get results that you can't get just talking on the phone; in part because you're effectively talking with a higher-up person, and because you can make your case a bit more clearly. You can actually tweet this StackExchange question directly, or word it yourself in a tweet/FB post/etc. On Twitter i'd link to here or somewhere else (too short), with something like \"\"@Orbitz @AmericanAir, you changed our trip and now it doesn't work with our special needs child. Any way you can help us out? [link to this q or a blog post somewhere]\"\". As far as a merchant dispute; it would realistically depend on the agreement you signed with Orbitz when you bought the tickets. Likely it includes some flexibility for them to change your plans if the airline cancels the flight. If it does, and they followed all of their policies correctly, then technically you shouldn't dispute the charge. It is possible that Chase might have some recourse on your behalf, though I don't think this qualifies for Trip Cancellation Insurance (Which you have through your Sapphire card ). It might be worth calling them, just to see. In the future, I would recommend booking through their site - not only do you get 25% bonus rewards when you use miles through there, which often is enough to offset the advantages of discount travel sites, but they're quite good at helping deal with these sorts of problems (as Sapphire is one of their top cards).\"", "title": "" } ]	[ { "docid": "447292", "text": "\"You must buy both tickets in 1 transaction and the purchased ticket cannot be purchased with miles. You'll pay full price (technically a \"\"paid published coach airfare\"\") for the first ticket and enter in your discount code for the companion fare which will ring up as $99 + fees ($118 in your example). If the regular price is $500, you'll book 2 tickets for $618 (one fare at $500 and companion fare at $118). Companion Fare Discount Code Q & A What is the Companion Fare Discount Code that comes with my credit card? The Companion Fare Discount Code is offered to holders of the Alaska Airlines Visa Signature® Card, The Platinum Plus® MasterCard® and the Visa® Business Card. This Discount Code entitles the cardholder to purchase one round-trip coach companion fare on Alaska Airlines from $121 (USD) ($99 base fare plus applicable taxes and fees from $22 depending on your Alaska Airlines flight itinerary) when traveling with another passenger on a paid published coach airfare on the same itinerary, booked at the same time. Mileage cannot be used as a form of payment, however mileage credit accrual is allowed for both travelers. Travelers are responsible for all applicable taxes, fees, surcharges and applicable checked baggage fees. The Companion Fare Discount Code is not valid with award travel, and cannot be combined with other discounts. Source: Alaska Air Companion Fair Q&A\"", "title": "" }, { "docid": "203544", "text": "You have no grounds for a refund. The flight took off on time, and you chose not to be on board. The fact that the airline could not guarantee ahead of time that the flight would leave on time is not relevant. You can certainly try to dispute the charge with the airline, and it sounds like you have done so. The airline correctly indicates that your dispute is unfounded. You can call up your credit card company and explain the situation, and they may accept your dispute. However, I am not aware of any credit card that would reimburse you (that is, issue a chargeback) in this situation. I'm not trying to be unsympathetic. It sucks that you felt you could not rely on the airline, and are now out some money. Fundamentally, though, this was your choice. The airline would be obligated to reimburse you the cost of your flight, or book you on another flight, if the flight was cancelled due to bad weather or other issues, but they owe you nothing if the flight took off on schedule.", "title": "" }, { "docid": "328760", "text": "Yes, they're referring to the credit card dispute (chargeback) process. In the case of dispute, credit card company will refund/freeze your charge so you don't have to pay until the dispute is resolved (or at all, if resolved in your favor). If the dispute is resolved in your favor, your credit card company will charge back the merchant's service provider which in turn will charge back (if it can) the merchant itself. So the one taking the most risk in this scenario is the merchant provider, this is why merchants that are high risk pay significantly higher fees or get dropped.", "title": "" }, { "docid": "583321", "text": "\"You should dispute the transaction with the credit card. Describe the story and attach the cash payment receipt, and dispute it as a duplicate charge. There will be no impact on your score, but if you don't have the cash receipt or any other proof of the alternative payment - it's your word against the merchant, and he has proof that you actually used your card there. So worst case - you just paid twice. If you dispute the charge and it is accepted - the merchant will pay a penalty. If it is not accepted - you may pay the penalty (on top of the original charge, depending on your credit card issuer - some charge for \"\"frivolous\"\" charge backs). It will take several more years for either the European merchants to learn how to deal with the US half-baked chip cards, or the American banks to start issue proper chip-and-PIN card as everywhere else. Either way, until then - if the merchant doesn't know how to handle signatures with the American credit cards - just don't use them. Pay cash. Given the controversy in the comments - my intention was not to say \"\"no, don't talk to the merchant\"\". From the description of the situation it didn't strike me as the merchant would even bother to consider the situation. A less than honest merchant knows that you have no leverage, and since you're a tourist and will probably not be returning there anyway - what's the worst you can do to them? A bad yelp review? You can definitely get in touch with the merchant and ask for a refund, but I would not expect much to come out from that.\"", "title": "" }, { "docid": "375170", "text": "A few reasons make sense: They have a defined process for rentals, risk assessment, and customer credit. Especially for a large corporation, making changes to that process is not trivial, adds risk/uncertainty, and will be costly. Such changes for a relatively small customer base might not makes sense. Many rental companies DO allow you to rent with a debit card. Why do some businesses take cash only? With a debit card, there is no third party guarantee. With a credit card, the cash is coming from a well-established third party who will pay (assuming no disputes) and has a well-established history of paying. Even if the merchant holds your account, it is still your cash under the control of you and your bank until the deposit clears the merchants bank. It is not surprising they view that as more risk and potentially not worth hassling with debit.", "title": "" }, { "docid": "469383", "text": "So, what's the point of a charge-back, if they simply take the word of the merchant? tl;dr: They don't. As both a merchant and a consumer I have been on both ends of credit card chargebacks, and have received what I consider to be mostly fair outcomes in all cases. Here are some examples: Takeaways from this: I strongly urge all consumers who are considering doing a chargeback to try to work with the merchant first, and use the CC dispute as a last resort. In general, you can think of the credit card dispute department like a judge. They hear the arguments presented by both sides, and consider them to the best of their ability. They don't always get it right, but they make their best attempt given the limited information they are provided.", "title": "" }, { "docid": "26996", "text": "Security in the merchant services system is mainly handled in two ways: 1) Before transactions are done, the business itself must go through an application process similar (but not identical) to getting a loan. Some high risk businesses must pay higher fees due to the increased likelihood of customer complaints. 2) When a customer disputes a transaction, that's a mark against the business. Get too many of these disputes, and your priviledge of accepting credit cards will be revoked, meaning you won't be able to again. It's in the merchant's best interest to verify customer's identity, because disputes cost them money directly. It's in the servicer's best interest to verify the businesses integrity, because fraud drives up the cost for everyone else. As a whole, it's quite a reactionary system, yet in practice it works remarkably well.", "title": "" }, { "docid": "461201", "text": "\"Wait a minute, this is a huge clickbait statistic. From the article: > Total overdraft fees totaled $33.3 billion in 2016, just shy of the $33.8 billion financial institutions collected in credit-card interchange fees They're comparing the _total_ sum of overdraft fees to the _total sum_ of interchange fees. While interchange fees have gone up over time, all the statistic in the story tells us is more people are using credit cards for transactions than \"\"before\"\". Merchants also have a huge choice in what sort of fees they pay, the processor they use (it's a surprisingly large market), and the rates vary by processor, type of merchant, risk to the merchant, type of business, type of card, and so on. As a note, the \"\"type of card\"\" is not just \"\"visa\"\" or \"\"amex\"\", but different cards from different issuers can have different interchange fees. That airline rewards card has a higher fee than that \"\"rebuild your credit\"\" secured (read: backed by a deposit) card. In short, this is a nonsense article that provides no useful comparison.\"", "title": "" }, { "docid": "176742", "text": "\"Personally, I would just dispute this one with your CC. I had a situation where a subscription I had cancelled the prior year was billed to me. I called up to have a refund issued, they couldn't find me in their system under three phone numbers and two addresses. The solution they proposed was \"\"send us your credit card statement with the charge circled,\"\" to which I responded \"\"there's no way in hell I'm sending you my CC statement.\"\" Then I disputed the charge with the CC bank and it was gone about two days later. I partially expect to have the same charge appear next year when they try to renew my non-existent subscription again. Now, whether or not this is a normal practice for the company, or just a call center person making a good-faith but insecure attempt to solve your problem is irrelevant. Fact of the matter is, you tried to resolve this with the merchant and the merchant asked for something that's likely outside the bounds of your CC Terms and Conditions; sending your entire number via email. Dispute it and move on. The dispute process exists for a reason.\"", "title": "" }, { "docid": "529786", "text": "\"The statement is (in laymans terms - if not in real terms) correct. Most credit cards (I know this to be true for VISA and Mastercard) have dispute processes and will do a chargeback on the merchant - ie take the money back from the supplier in cases where you don't receive the goods or other fraud - Particularly if they can't produce a signature and (for transactions which are not face-to-face) a tracking number. Your exact rights will vary by bank, but mostly they need to follow the guidelines set by the Credit Card company - and you do need to be a bit careful - if you received goods which were fake or a dispute arises you may be up for shipping the goods back to the merchant - and you have a limited - but reasonable time - in which to make the dispute. (The statement \"\"the money is the banks\"\" is not technically true, there is no money involved until you pay it, only credit [ they are very different, but almost no-one knows that, I communicated with a Minister of Finance on the topic], but this is quite technical and as a layman not something you need to worry about here)\"", "title": "" }, { "docid": "401254", "text": "\"I'm going to go with \"\"ridiculous notion.\"\" :) The vast majority of businesses are legitimate, run by honest people trying to earn a living for themselves and their employees. These days, almost all of them accept credit cards. Crooked businesses are a very small minority. When a bad business over charges you, you dispute the charge, and you get your money back. But that's not all that happens. The bad merchant pays penalties for this, and if it happens more than a couple of times, the merchant loses their merchant account with their bank, which means that they lose their ability to accept credit card payments anymore. A crooked business is not able to rob people via credit card for very long at all. A whitelist would certainly not be able to include every legitimate business. And a blacklist would never be able to be kept up-to-date, as bad businesses come and go continuously; as soon as a business was added to the blacklist, they would lose their merchant account and would no longer need to be on the list. What you are describing is very rare. My brother once had a bad experience with a tech support company where they were repeatedly charging him for a service they never performed. But a credit card chargeback took care of it. If that company made a habit of that, I'm sure that they got in trouble with their bank. Instead, the most common credit card fraud happens when crooks use your credit card at perfectly legitimate businesses. But your whitelist/blacklist wouldn't help you with that at all.\"", "title": "" }, { "docid": "169287", "text": "Your simplest option, and probably the only reasonable one, is to dispute the original charge with your bank. Since you used a debit card and not a credit card, you don't have quite as much protection, but you still can dispute the charge and ask your bank to step in and help. See this debit card dispute article for more information on disputing a charge for a debit card. You may or may not have a case here, depending on the specifics. If the merchant accepted your payment without letting you know you should have used paypal, you may have a shot at getting the full refund; but if it was clearly labelled that you should have used paypal, it may be harder.", "title": "" }, { "docid": "266952", "text": "\"As a rule of thumb, go in the order of proximity to the transaction. This would typically mean: Side note: I own a website that provides an online service that accepts PayPal and credit cards (via PayPal), and I personally have experience with all 3 of the above options. I can tell you from the merchant's point of view that I would also prefer the same order. I've had people contact my customer service department asking for a refund and we always immediately comply. Some people never contact us and just file a dispute directly with PayPal, and although refunding through the PayPal dispute is just as easy as refunding directly, it always makes me ask, \"\"Why didn't they just contact us first?\"\" One time we had a customer skip us and PayPal, and filed a dispute directly with their Credit Card. The CC company contacted PayPal and PayPal contacted us. The process was the same from my point of view, I just clicked a button saying issue refund. But my $5 refund cost me an additional $20 due to the CC dispute. Now that I know this I will never approve a CC dispute again. Anytime one happens I would just issue a refund directly, and then notify the dispute that their CC has already been refunded, which should end the dispute.\"", "title": "" }, { "docid": "36801", "text": "There are numerous reasons that go beyond the immediate requirement for access to credit. Many people just plain don't like carrying cash. Before electronic debit cards became mainstream about the only way to pay for online services was with a credit card. This has now changed just about everywhere except a large number of airlines which still only sell online tickets via a credit card payment. And then there are all those countries where governments (and some banks) have decided to charge merchants more when customers use debit cards. If you don't like carrying cash then you may find that the only card you can use is a credit card. These concerns are gradually disappearing and at some stage someone is likely to offer a combined debit-credit card. At which point you'll probably get credit whether you like it or not.", "title": "" }, { "docid": "566598", "text": "\"Most credit cards allow you to take \"\"cash advances\"\", but the fees and limits for cash advances are different than for regular purchases. You can buy stock after taking a cash advance from your credit card. When you make a cash advance, you normally pay the credit card company a fee. When you make a regular purchase, the merchant (ie, the stockbroker) pays a fee. Additionally, credit card companies can make merchants wait up to 3 months to actually receive the money, in case the transaction is disputed. Your stockbroker is unlikely to want to pay the fee, accept the delay in receiving the funds, and risking that you will dispute the transaction. Having said that, many FOREX brokers will accept credit card deposits (treated as purchases), although FOREX can be considerably riskier than the stock market. Of course, if you max out your credit cards and lose all your money, you can normally negotiate to pay back the debt for less than the original amount, especially since it's unsecured debt.\"", "title": "" }, { "docid": "366735", "text": "You should start a dispute with the credit card company, and they might be able to recover some/all of the money. Usually, if you act fast enough, credit companies (on the merchant's side) have enough of the deposits not yet disbursed to the merchant, and they'll just reverse the charge. The earlier you start the process - the more chances you have. Otherwise you'll have to sue, I'm not familiar with the Canadian legal system.", "title": "" }, { "docid": "452980", "text": "No, the credit company will not remove the $20. Your merchant (the airline) charged in their local currency, the equivalent of $1000. That is also what they refunded. The $20 are yours to keep.", "title": "" }, { "docid": "125827", "text": "When you initiate a chargeback, the merchant has the right to dispute the chargeback. If they can provide proof that the purchase actually took place, the chargeback will fail. We don't know all the details of your situation, of course, but it appears from what you have said that the tax chain probably has documents that you signed agreeing to the charges. They prepared your return (even if they did a poor job), and so from their perspective, they have decided that they deserve to be paid. Whether or not they did a good job is a matter of opinion, of course; their position might be that they did it correctly, and the second business did it poorly. The chargeback is a powerful tool, but it is not a magic button that makes a charge disappear. If the merchant can show that a sale did indeed take place and show that the proper amount was charged, the chargeback will fail. For a service, it isn't enough usually to simply state that you were unsatisfied; if you received the service at the agreed-upon price, the charge is valid. A chargeback is sort of a nuclear option when it comes to getting a refund. There are negative ramifications and expenses every time a merchant gets a chargeback (even if they ultimately win), and so often they will be willing to work something out to avoid a chargeback. You should go to the merchant first, if you can, and ask for a refund before considering the chargeback option. If you file a chargeback without even giving them the opportunity to work it out with you, the merchant will usually want to fight back.", "title": "" }, { "docid": "423320", "text": "\"In response: 1 - So every disease that isn't glamorous enough to generate independent financing for research isn't going to get cured. Gotcha. More people die of colon and rectal cancer per year than breast cancer, but you'll never see a \"\"Save the poopers\"\" walk, because that shit doesn't sell yogurt. Most \"\"awareness\"\" fundraisers don't do anything (or do comparatively little) for research. They're more about supporting survivors. Yet, the CDC is one of, if not the most successful federally-funded program ever. It's wiped two diseases off the face of the earth. No bake sale is going to do that. Public health is a market failure - and the CDC has managed to give away 80% of its funding to third-party research and programming in such a way that it has accomplished goals including eradication of disease. 2 - First, [comptrollers](http://en.wikipedia.org/wiki/Comptroller) are financial reporting and accounting oversight managers. The guys who wear headsets are aircraft controllers. So which airline will have the flight controllers? Will every small operation have to have its own controller in every tower at every airport it lands at? Or will the airlines large enough to have controllers simply charge everyone else to use theirs? Even more interesting, without oversight, what's to stop misinformation being fed between controllers with different carriers, for the profit of individual companies? The FAA also inspects aircraft during manufacturing and maintenance. If everyone who builds an aircraft is responsible for funding that themselves, or getting some third-party certification (yet another government organization must be created, or somehow exist profitably by magic), that's going to kill the world of experimental aircraft outside of the big three. 3 - You really didn't google anything before you got into this. No, the police don't enforce FCC regulations; that all falls under the FCC's jurisdiction and they only rely on locals for backup security during raids, which are rare. Leaving it to civil suits means anyone with the largest pockets gets to broadcast the loudest. Leaving it to the locals means training local police to fox hunt. Minor disputes over frequencies? That's plainly naive; nearly everyone with a transmitter has more wattage available than they're legally permitted to use. Broadcast wattage increases are delicately negotiated, petitioned, debated and re-petitioned, and then turned up. Elimination of regulation wouldn't even be settled at the town level - you're talking inter-county and interstate disputes. I personally broadcasted at a station that was greenlighted to 15,000W and we were heard in the tristate area and Canada - good luck coming to international accord on broadcasting standards without a federal body to speak for your industry. I'm not even addressing your last paragraph. It's just straw-manning and caricaturization.\"", "title": "" }, { "docid": "544451", "text": "I'll give it a shot, though I know nearly nothing about airlines. 1% is a lot when your revenue is very high. Lets say a plane can have 200 people on it. Plane tickets are a lot, so each person is charged $700 in this example. That's 140K in gross revenue per trip. 1% of that is $1400. You have several trips a day per plane. Lets say 5 trips a day per plane. Each plane is netting $7000 a day. Or around $2.5 million in profit a year. Lets say a commercial plane that has a capacity of 200, costs around $50 million. That's a 20 year ROI. Up your margins to 2%, now you're at 10 year ROI. Plus depreciation. You get to depreciate that $50 million over the course of X years. Basically making all of the profits the airline gets, tax free due to their insane amount of depreciation. Pair this income with cheap oil, and a smart CEO that can cut costs, and you have a cash cow on your hands. And given the fact that a lot of airlines have a ton of planes already depreciated to $0 that aren't on their books any more, you may be able to buy the airline for a fraction of their net assets. Margins are important, but it's all relative. Edit: Changed numbers to prove my point, and because I am not a smart man", "title": "" }, { "docid": "582607", "text": "\"They stated ebooks are only 1% of their revenue. Amazon is responsible for 65% of all online new book sales, print included. Amazon and Hachette's disagreement on ebook pricing shouldn't affect the sales of Hachette's print books available on the site, but Amazon is increasing ship times, removing the ability to pre-order books, raised the prices of existing books, and lowering the chances that Hachette's book show up in their \"\"you might also like\"\" section. ([source](http://theverge.com/2014/8/9/5985901/amazon-hachette-contract-dispute-storystream)) I guess those changes might not add up to half of Hachette's revenue (I was mistakenly remembering [when Amazon removed the \"\"buy\"\" button from Macmillon's books in 2010](http://www.nytimes.com/2010/01/30/technology/30amazon.html) because of a similar dispute over ebook pricing), but you can bet their attempts to decrease Hachette's print book's availability, accessibility, and visibility on their site is having a very significant effect on their income. Again, Amazon is decreasing the availability of a publisher's print books because of a dispute over ebook pricing. That's nuts.\"", "title": "" }, { "docid": "214139", "text": "\"American Express was originally a mail business that moved into money-orders. Traditionally their cards have been charge cards instead of a credit card (though they have credit products now as well). They've been marketed specifically as a \"\"premium\"\" product for people who have a significant amount of money (and are willing to pay a significant fee for premium services such as AmEx's good airline miles). As such, Visa and MasterCard are more widespread. Additionally, the fees that Visa and MasterCard charge merchants are typically lower (Wikipedia says 2%, as compared to AmEx's 2.5%, at least in the US). So: American Express gets less business as a company, but they charge higher fees to make up for it. Merchants will only accept the higher fees when they want to serve people who have a lot of money to spend (or if they can negotiate a discount).\"", "title": "" }, { "docid": "393639", "text": "\"You should seriously just stop talking. The term legacy employees refers to legacy cost structures. Costs that linger from a time when the competitive environment was different than it is today are referred to as legacy costs. It is not derogatory. Take airlines, for example. Airlines used to have incredible legacy costs from unionized employees incurred at a time when the airline industry was regulated. Regulation kept new airlines from starting up, so airlines could very easily afford to pay for pensions, huge benefits, massive salaries, etc. The few airlines in existence then had control over the industry. Then the airlines were deregulated and anyone could start one up. Suddenly, the airlines that could afford massive pensions in the days where they effectively controlled pricing could no longer afford these pensions and benefits when competitors did not offer the same benefits to their employees. Hence, every single \"\"legacy\"\" airline went bankrupt over the next few decades.\"", "title": "" }, { "docid": "308383", "text": "My experience is in the United States only. In the past, American Express marketed its products as more exclusive and prestigious than other cards. There was an attempt to give the impression that cardholders were more qualified financially. In return, fees were higher both to merchants and to cardholders. At the time (early 1990's), it was not common to use credit cards for small purchases, such as groceries or fast food. Credit cards were used for larger purchases such as jewelry or electronics or dinner in a nicer restaurant. Once it became popular to use credit cards for everyday purchases, the demand for customers using credit cards changed to the highest number of people instead of people of higher status. At that point, Visa (and to a lesser extent Mastercard) transaction volume increased dramatically. Merchants needed the largest number of customers with cards, not the most financially stable. As Visa volume grew, and people started using Visa for small purchases, the use of American Express decreased as their habits changed (once someone got used to pulling out Visa, they did it in every situation). Merchants are less willing to go through the extra hassle of accepting cards that are used by fewer people. Over time, I suspect this process led to the gap between Visa and American Express. As a merchant, in order to accept credit cards, you have to set up a bank account and maintain a merchant account. Accepting Visa, MC and Discover can all be done through one account, but American Express has traditionally required a separate relationship, as well as its own set of rules and fees that were generally higher. Since there are relatively few American Express cardholders compared to Visa, there is doubt about whether it is worth it accept the card. It depends upon the customer base. Fine restaurants still generally accept American Express.", "title": "" }, { "docid": "94084", "text": "Read your link. Thanks. The basic idea is that capitalism will work it out. And that each of us will pay a security agency to handle our disputes, and that rival security agencies will collaborate and negotiate with each other. And that private courts will be fair to protect their brand. This overlooks some harsh realities that already exist with capitalism. Customers generally do not have time to purchase based on accurate information for every product. For example, airlines compete almost solely on price. Insurance companies compete on price and provide horrible, sometimes fraudulent service. But customers are left in the dark (who is to say the insurer committed fraud if it disputes it?) Banks operate with gross incompetence and deceipt and are left untouched by the justice system. We have already discovered that just letting corporations operate without an restrictions creates serious problems. There has to be force that tempers their worst tendencies, even if that force (government) is imperfect. I remain confused why people think that corporations are somehow more trustworthy and efficient than government agencies. Or that corporations can be used to address externalities.", "title": "" }, { "docid": "490955", "text": "\"Executive summary: It sounds like the merchant just did an authorization then cancelled that authorization when you cancelled the order, so there was never an actual charge so you'll never see an actual refund and there's no money to \"\"claim\"\". More detail: From your second paragraph, it sounds like they just did an authorization but never posted the transaction. A credit card authorization is basically the merchant asking your credit card company \"\"Does sandi have enough credit to pay this amount and if so please reserve that amount for a bit.\"\" The authorization will decrease the total credit you have available on the card, but it's not actually a charge, so if your billing cycle ends, it won't show up on your statement. Depending on which company issued your credit card, you may be able to see the authorization online, usually labelled something like \"\"Pending transactions\"\". Even if your credit card company doesn't show pending transactions, you'll see a decrease in your available credit, however you shouldn't see an increase in your balance. The next step, and the only way the original merchant gets paid, is for the merchant to actually post a transaction to your card. Then it becomes a real charge that will show up on your next credit card statement and you'll be expected to pay it (unless you dispute the charge, but that's a different issue). If the charge is for the same amount as the authorization, the authorization will go away (it's now been converted to an actual charge). If the amounts are different, or the merchant never posts a transaction, the authorization will be removed by your credit card company automatically after a certain amount of time. So it sounds like you placed the order, the merchant did an authorization to make sure you could pay for it and to reserve the money, but then you cancelled the order before the merchant could post the transaction, so you were never really charged for it. The merchant then cancelled the authorization (going by the start of your third paragraph). So there was never an actual transaction posted, you were never charged, and you never really owed any money. Your available credit went down for a bit, but now should be restored to what it was before you placed the order. You'll never see an actual refund reflected on your credit card statement because there was no actual transaction.\"", "title": "" }, { "docid": "484261", "text": "Generally most businesses will not, but it's not uncommon. Not sure about other countries, but in Australia merchants here generally have to pay VISA or Mastercard a commission if the consumer chooses to use credit. So even if they don't levy a charge, they may have a minimum purchase amount which you can use credit cards for. Amongst some of the ones who do include... Pretty much all of the budget airlines like (Virgin) airlines. I think there's been some outrage with them cause they charge $4.50 per person per trip which in some cases is greater than the transaction cost they have to pay to the credit card companies. Aldi Supermarket link they're kind of a budget supermarket. You got to pay for shopping bags and also charge 1% more for credit card. On a side note, we also have a thing called EFTPOS here (http://en.wikipedia.org/wiki/EFTPOS) which is a debit card network. I think this network charges less commission because generally, a lof of businesses that charge for credit may not charge for EFTPOS. I also feel EFTPOS is also more secure as it requires a pin number, unlike a credit card which requires a signature.", "title": "" }, { "docid": "430377", "text": "As a general premise: In most of the online transactions in case of dispute the benefit of doubt is given to the customer. IE if the customer refuses to pay and claims that its not his transaction, the card company reverses the charges and does not pay the merchant (or recovers if its already paid). There are many types of online vendors who use a variety of methods to ensure that they are not at loss. Some of these are:", "title": "" }, { "docid": "382838", "text": "If you paid by credit card, file a dispute with the credit card company. They will credit you the money immediately while they investigate. The burden of proof will then be on the merchant. Keep your documents handy in case you need them: USPS receipt, proof of delivery, copies of all correspondance, etc. File the credit card chargeback now, because there are time limits. The FTC has more information.", "title": "" }, { "docid": "301455", "text": "You will need to first try and get the seller to refund. (Get the name of the person you talked to and a date and time). Then you can contact the bank the card was issued through and dispute the charge. I would make sure that you retain any proof that you purchased one item and received something other than what you purchased. The seller does have recourse if they did fulfill their side of the transaction but if they are a legitimate merchant and actually sent you the wrong product most will not bother.", "title": "" } ]
10102	Cons of withdrawing money from an Roth IRA account?	[ { "docid": "595042", "text": "\"One \"\"con\"\" I have not yet seen mentioned: retirement accounts are generally protected from creditors in a bankruptcy. There are limits and exceptions, Roth has a 1.2 million dollar limit and can be split by a divorce QDRO for instance. Link Since it seems you have no income this year, you may may be raiding your IRA for living expenses. If there is a chance you may declare bankruptcy in the next year or so, consider doing that first and raid the IRA for seed money after.\"", "title": "" }, { "docid": "84334", "text": "First thing to note is that contributions (i.e. the total of all the amounts that you directly contributed into Roth IRA at any point in time) to a Roth IRA can be withdrawn at any time, without needing any reason, without any tax or penalty. Early withdrawal (early because you are under 59.5) of earnings, on the other hand, will incur tax and penalty. (I didn't go into withdrawal of conversions as those are a little more complex.) When you withdraw, contributions come out first, so as long as you don't withdraw more than the amount of past contributions, you won't have any tax or penalty. And if it's not going to have tax, it doesn't really matter if you do it this year or next year. If you need to dip into the earnings, however, then maybe it would be better to do this year so it will be taxed at lower rates.", "title": "" }, { "docid": "122404", "text": "In a year with no income, the best advice is to convert existing IRA money to Roth. This lets you take advantage of the 'zero' bracket, the combination of your exemption and standard deduction. This adds to $10,300 for a single person. Other than that, if you are determined to take the money out, just do it. There would be a 10% penalty of the growth, but the original deposit comes out tax free anyway. Edit - There's a rule that if you sell your entire Roth account (i.e. all Roth accounts, you can't pick one of a few) and have a loss, you can take that loss. (Per Dilip's comment, this strategy is pretty moot, it's not a loss taken against other income as a stock loss would potentially be))", "title": "" } ]	[ { "docid": "398520", "text": "Don’t take the cash deposit whatever you do. This is a retirement savings vehicle after all and you want to keep this money designated as such. You have 3 options: 1) Rollover the old 401k to the new 401k. Once Your new plan is setup you can call who ever runs that plan and ask them how to get started. It will require you filling out a form with the old 401k provider and they’ll transfer the balance of your account directly to the new 401k. 2) Rollover the old 401k to a Traditional IRA. This involves opening a new traditional IRA if you don’t already have one (I assume you don’t). Vanguard is a reddit favorite and I can vouch for them as Well. Other shops like Fidelity and Schwab are also good but since Vanguard is very low cost and has great service it’s usually a good choice especially for beginners. 3) Convert the old 401k to a ROTH IRA. This is essentially the same as Step 2, the difference is you’ll owe taxes on the balance you convert. Why would you voluntarily want to pay taxes f you can avoid them with options 1 or 2? The beauty of the ROTH is you only pay taxes on the money you contribute to the ROTH, then it grows tax free and when you’re retired you get to withdraw it tax free as well. (The money contained in a 401k or a traditional IRA is taxed when you withdraw in retirement). My $.02. 401k accounts typically have higher fees than IRAs, even if they own the same mutual funds the expense ratios are usually more in the 401k. The last 2 times I’ve changed jobs I’ve converted the 401k money into my ROTH IRA. If it’s a small sum of money and/or you can afford to pay the taxes on the money I’d suggest doing the same. You can read up heavily on the pros/cons of ROTH vs Traditional but My personal strategy is to have 2 “buckets” or money when I retire (some in ROTH and some in Traditional). I can withdraw as much money from the Traditional account until I Max out the lowest Tax bracket and then pull any other money I need from the ROTH accounts that are tax free.This allows you to keep taxes fairly low in retirement. If you don’t have a ROTH now this is a great way to start one.", "title": "" }, { "docid": "252373", "text": "\"Yes, it is possible to withdraw money from your Roth IRA before retirement (but I wouldn't necessarily advise you to do so.) Here's the good news, and the bad news: The good news: Unlike a traditional IRA, money contributed to a Roth IRA is done so on an after-tax basis, meaning you don't benefit from a tax deduction on contributions. So, the money you withdraw from your Roth IRA will not be taxed entirely as ordinary income. In fact, you are allowed to withdraw the amount of your original contributions (also known as basis) without any taxes or penalties. Let's imagine you originally deposited $9000 of that current $10K total value – then in such a case, $9000 could be withdrawn tax and penalty free. The bad news: When it comes to the investment earnings – the other $1000 in my example – it's a different story: Since you wouldn't be age 59 1/2 at the time of withdrawal, any money taken out beyond your original contributions would be considered a non-qualified withdrawal and subject to both ordinary income taxes plus a 10% early withdrawal penalty. Ouch! Perhaps you might want to restrict your withdrawal to your original contributions. I would imagine if you've had the account for such a short period of time that much or all of your account value is original contributions anyway. A good article about the rules for early IRA withdrawals is About.com's Tax Penalty for Early Distribution of Retirement Funds. Note: If your Roth IRA funds were the result of a rollover from another account type, other rules may apply. See Roth IRA (Wikipedia) for more detail; search for \"\"rollover\"\". Regarding the withdrawal process itself and the timing, you should check with your account custodian on how to proceed.\"", "title": "" }, { "docid": "2128", "text": "If the IRA is costing you $100 a year, you should almost certainly transfer it to a cheaper provider, regardless of whether you're going to withdraw anything. You can transfer the IRA to another provider that doesn't charge you the fees. Or you can convert it to Roth and combine it with your existing Roth. Either way, you will keep all the money, and save $100 per year in the future. If you want to take money out of your retirement accounts, you should take it out of your Roth IRA, because you can withdraw contributions (i.e., up to the amount you contributed) from the Roth without tax or penalty. Whether you should withdraw anything from your retirement accounts is a different question. If you're already maxing out your Roth IRA, and you have sufficient retirement savings, you could just instead plow that $5500 into your student loans. (If you can afford it, of course, it'd be better to just pay the $7500 from your income and still contribute to the retirement accounts.) There's no reason to withdraw from retirement accounts to pay loans when you could just divert current income for that purpose instead.", "title": "" }, { "docid": "144751", "text": "\"There's currently not much reason to keep around a long-term non-deductible Traditional IRA in my opinion -- a Roth IRA is almost strictly better. Think about it: a non-deductible Traditional IRA vs. a Roth IRA of the same amount. In both cases, contributions are after-tax (so no tax deduction). But when you withdraw, for the Roth IRA you don't have to pay tax, and for the non-deductible Traditional IRA, you have to pay tax on the \"\"earnings\"\". A Roth IRA can be contributed to at pretty much any income level, thanks to the backdoor Roth IRA process (which uses a temporary non-deductible Traditional IRA in the process). So there is not much reason for a long-term non-deductible Traditional IRA. As for your question, a non-deductible Traditional IRA vs. a taxable account. Well, a non-deductible Traditional IRA is contributed to with after-tax money, and taxed on the earnings only on withdrawal. So the taxation is almost identical to things like stocks and homes, where the gain is not realized until the thing is sold. However, compared to things like savings accounts and bonds, where you get taxed on the interest yearly, it is much better. Every time you get taxed on gains like this, it is taxing gains earned from after-tax money, so if you think of an amount of money as being equivalent to the amount of money it grows to over time (time value of money), then it is taxing money that is (or grown from money that is) already taxed. So it is better to have this only happen at the end at withdrawal than every year.\"", "title": "" }, { "docid": "561636", "text": "You're misunderstanding the concept of retirement savings. IRA distributions are taxed, in their entirety, as ordinary income. If you withdraw before the retirement age, additional 10% penalty is added. Investment income has preferential treatment - long term capital gains and qualified dividends are taxed at lower rates than ordinary income. However, IRA contributions are tax deductible. I.e.: you don't pay taxes on the amounts contributed to the IRA when you earned the money, only when you withdraw. In the mean time, the money is growing, tax free, based on your investments. Anything inside the IRA is tax free, including dividends, distributions (from funds to your IRA, not from IRA to you), capital gains, etc. This is very powerful, when taking into account the compounding effect of reinvesting your dividends/sale proceeds without taking a chunk out for taxes. Consider you make an investment in a fund that appreciated 100% in half a year. You cash out to reinvest in something less volatile to lock the gains. In a regular account - you pay taxes when you sell, based on your brackets. In the IRA you reinvest all of your sale proceeds. That would be ~25-35% more of the gains to reinvest and continue working for you! However, if you decide to withdraw - you pay ordinary rate taxes on the whole amount. If you would invest in a single fund for 30 years in a regular account - you'd pay 20% capital gains tax (on the appreciation, not the dividends). In the IRA, if you invest in the same fund for the same period - you'll pay your ordinary income rates. However, the benefit of reinvesting dividends tax-free softens the blow somewhat, but that's much harder to quantify. Bottom line: if you want to plan for retirement - plan for retirment. Otherwise - IRA is not an investment vehicle. Also consider Roth IRA/conversions. Roth IRA has the benefit of tax free distributions at retirement. If your current tax bracket is at 20%, for example, contributing $5K to Roth IRA instead of a traditional will cost you $1K of taxes now, but will save you all the taxes during the retirement (for the distributions from the Roth IRA). It may be very much worth your while, especially if you can contribute directly to Roth IRA (there are some income limitations and phaseouts). You can withdraw contributions (but not earnings) from Roth IRA - something you cannot do with a traditional IRA.", "title": "" }, { "docid": "545184", "text": "As far as I know, there is no direct equivalent. An IRA is subject to many rules. Not only are there early withdrawal penalties, but the ability to deduct contributions to an IRA phases out with one's income level. Qualified withdrawals from an IRA won't have penalties, but they will be taxed as income. Contributions to a Roth IRA can be made post-tax and the resulting gains will be tax free, but they cannot be withdrawn early. Another tax-deductable investment is a 529 plan. These can be withdrawn from at any time, but there is a penalty if the money is not used for educational purposes. A 401K or similar employer-sponsored fund is made with pre-tax dollars unless it is designated as a Roth 401K. These plans also require money to be withdrawn specifically for retirement, with a 10% penalty for early withdrawal. Qualifying withdrawals from a regular retirement plan are taxed as income, those from a Roth plan are not (as with an IRA). Money can be made harder to get at by investing in all of the types of funds you can invest in using an IRA through the same brokers under a different type of account, but the contribution will be made with post-tax, non-deductable dollars and the gains will be taxed.", "title": "" }, { "docid": "175968", "text": "\"In a Roth IRA scenario, this $5,000 would be reduced to $3,750 if we assume a (nice and round) 25% tax rate. For the Traditional IRA, the full $5,000 would be invested. No, that's not how it works. Taxes aren't removed from your Roth account. You'll have $5,000 invested either way. The difference is that you'll have a tax deduction if you invest in a traditional IRA, but not a Roth. So you'll \"\"save\"\" $1,250 in taxes up front if you invest in a traditional IRA versus a Roth. The flip side is when you withdraw the money. Since you've already paid tax on the Roth investment, and it grows tax free, you'll pay no tax when you withdraw it. But you'll pay tax on the investment and the gains when you withdraw from a traditional IRA. Using your numbers, you'd pay tax on $2.2MM from the traditional IRA, but NO TAX on $2.2MM from the Roth. At that point, you've saved over $500,000 in taxes. Now if you invested the tax savings from the traditional IRA and it earned the same amount, then yes, you'd end up in the same place in the end, provided you have the same marginal tax rate. But I suspect that most don't invest that savings, and if you withdraw significant amount, you'll likely move into higher tax brackets. In your example, suppose you only had $3,750 of \"\"discretionary\"\" income that you could put toward retirement. You could put $5,000 in a traditional IRA (since you'll get a $1,250 tax deduction), or $3,750 in a Roth. Then your math works out the same. If you invest the same amount in either, though, the math on the Roth is a no-brainer.\"", "title": "" }, { "docid": "403103", "text": "The primary advantage of an IRA or 401k is you get taxed effectively one time on the money (when you contribute for Roth, or when you withdraw for Traditional), whereas you get taxed effectively multiple times on some of the money in a taxable account (on all the money when you contribute, plus on the earnings part when you withdraw). Of course, you have to be able to withdraw without penalty for it to be optimally advantageous. And you said you want to retire decades early, so that is probably not retirement age. However, withdrawing early does not necessarily mean you have a penalty. For example: you can withdraw contributions to a Roth IRA at any time without tax or penalty; Roth 401k can be rolled over into Roth IRA; other types of accounts can be converted to Roth IRA and the principal of the conversion can be withdrawn after 5 years without penalty.", "title": "" }, { "docid": "168530", "text": "\"I spent some time searching, and couldn't find the answer written explicitly in IRS regulations. What I did find was this chart from the irs showing that nonqualified distributions from a Roth 401k are pro-rated between contributions and earnings. It is well documented that you can't withdraw any money early or tax free (even contributions) from a Roth 401k (\"\"Designated Roth Account\"\" in IRS parlance) that has made any money. source You can do a direct rollover from a \"\"Designated Roth Account\"\" to a Roth IRA and the basis describing contributions vs. earnings is preserved. source And there is plenty of evidence showing you can withdraw contributions from a Roth IRA without penalty. source All that being said, I can't find anything from the IRS that says this is a legitimate strategy.\"", "title": "" }, { "docid": "59600", "text": "It is really hard to tell where you should withdraw money from. So instead, I'll give you some pointers to make it easier for you to make the decision for yourself, while keeping the answer useful to others as well. I have 3 401ks, ... and some has post tax, non Roth money Why keeping 3 401ks? You can roll them over into an IRA or the one 401k which is still active (I assume here you're not currently employed with 3 different employers). This will also help you avoiding fees for too low balances on your IRAs. However, for the 401k with after tax (not Roth) balance - read the next part carefully. Post tax amounts are your basis. Generally, it is not a good idea to keep post-tax amounts in 401k/IRA, you usually do post-tax contributions to convert them to Roth ASAP. Withdrawing from 401k with basis may become a mess since you'll have to account for the basis portion of each withdrawal. Especially if you pool it with IRAs, so that one - don't rollover, keep it separately to make that accounting easier. I also have several smaller IRAs and Roth IRAs, Keep in mind the RMD requirements. Roth IRAs don't have those, and are non-taxable income, so you would probably want to keep them as long as possible. This is relevant for 401k as well. Again, consolidating will help you with the fees. I'm concerned about having easily accessible cash for emergencies. I suggest keeping Roth amounts for this purpose as they're easily accessible and bear no taxable consequence. Other than emergencies don't touch them for as long as you can. I do have some other money in taxable investments For those, consider re-balancing to a more conservative style, but beware of the capital gains taxes if you have a lot of gains accumulated. You may want consider loss-harvesting (selling the positions in the red) to liquidate investments without adverse tax consequences while getting some of your cash back into the checking account. In any case, depending on your tax bracket, capital gains taxes are generally lower (down to 0%) than ordinary income taxes (which is what you pay for IRA/401k withdrawals), so you would probably want to start with these, after careful planning and taking the RMD and the Social Security (if you're getting any) into account.", "title": "" }, { "docid": "305855", "text": "I think you're missing several key issues here. First for the facts: IRA contributions are $5500 a year maximum (currently, it changes with inflation), i.e.: you cannot deposit $10K in an IRA account in a single year. IRA withdrawals can only be made if you have something liquid in the IRA. You cannot withdraw from Lending Club IRA unless you manage to sell the notes currently held by you there. Roth IRA is funded with after-tax money, and you can withdraw your deposits in Roth IRA any time for any reason. No 10K limit there, only limited by what you deposited. However the main thing you're missing is this: You can withdraw up to $10K from your IRA for first home purchase without penalty. Pay attention: not without tax but without penalty. So what is the point in depositing $10k into IRA just to withdraw it the next year?", "title": "" }, { "docid": "32671", "text": "\"The receiving Roth IRA custodian will almost certainly not charge you anything; they are eager to get their hands on the money. In fact, the easiest and most efficient way is to fill out the forms for opening a Roth IRA account with the new custodian (most of this can be done online, but it might be necessary to print out a paper form, sign it and send/fax it to the company), tell them that the Roth IRA will be funded by a trustee-to-trustee transfer from the current custodian, and tell them to go get the money from the online bank who is the current custodian of your Roth IRA account. Don't approach your online bank and tell them to send the money to your new Roth IRA custodian; it will cost money and take more time and the likelihood of a screw-up is way too high. The current custodian might charge you a fee for closing the account, or for \"\"breaking a CD\"\" if that savings account is a CD and you are withdrawing the money before the maturity date of the CD. This will be spelled out in the Roth IRA custodial agreement that you accepted when you opened the account (but most likely did not read in full when you received it, and might even have discarded). One final note: with just $11K, please do not open a brokerage account for your Roth IRA and invest in stocks, bonds etc. For now, invest all your Roth IRA in a single low-cost mutual fund (preferably an index fund such as the Vanguard S&P 500 Index fund or Fidelity Spartan 500 fund); you can branch out into more funds when you have more money in your Roth IRA. Investing in these funds does not need you to have a brokerage account; you can do it directly on the fund's website. Avoid (for now) the siren song of Exchange-Traded Funds (ETFs) because you need to have a brokerage account to buy and sell them. When you have more money in your Roth IRA account, say in ten years' time, you can start investing in individual stocks, ETFs and the like through a brokerage account, but don't do it now.\"", "title": "" }, { "docid": "585422", "text": "\"The different things in each calculator are showing you a bunch of different things. In the \"\"Roth IRA calculator\"\", it is comparing what you would have in the end after contributing and withdrawing from a Roth IRA, with what you would have in the end with a taxable account (i.e. an investment outside of any IRAs). In the \"\"Traditional IRA calculator\"\", the \"\"IRA after taxes\"\" shows you what you would have in the end after contributing and withdrawing from a pre-tax Traditional IRA. The \"\"IRA before taxes\"\" simply shows the same amount before you pay the taxes on withdrawal, which is not a useful number. So if you want to compare Roth IRA vs. Traditional IRA, you want to compare the \"\"Roth IRA\"\" from the Roth IRA Calculator and the \"\"IRA after taxes\"\" from the Traditional IRA calculator, but there are some things you need to be aware of to make a fair comparison, because if you just plug in the same numbers you are going to get a very unfair comparison (it will look like Roth IRA is a lot \"\"better\"\" even though it's not). The Roth IRA contribution is after-tax, whereas a (pre-tax) Traditional IRA contribution is pre-tax, and an after-tax dollar is much more than a pre-tax dollar, so if you put in the same nominal contribution amount, you are actually contributing much \"\"more\"\" from your wallet in the Roth IRA case. To make a fair comparison, you would need to start with the same pre-tax amount, and put in a Roth IRA contribution amount that corresponds to the equivalent amount after taxes. So for example, a $5000 pre-tax amount with 25% taxes is equivalent to $5000 * 0.75 = $3750, so you would put in $5000 for Traditional IRA contribution vs. $3750 for Roth IRA contribution. Note that if you have the same flat tax rate at contribution and at withdrawal, (pre-tax) Traditional IRA and Roth IRA are exactly the same, and you can see this by putting in 25% for the \"\"Retirement tax rate\"\" in the Traditional IRA calculator (we already assumed 25% tax rate for Roth IRA when calculating the contribution). You will see that Traditional IRA would be better in a lower retirement tax rate (e.g. 15%), whereas Roth IRA would be higher in a higher retirement tax rate.\"", "title": "" }, { "docid": "67410", "text": "\"The tax code is a hodgepodge of rules that are often tough to explain. The reality is that it's our Congress that writes the tax code, and they often have conflicting goals among themselves. In theory, someone said \"\"How about we force withdrawals at some point. After all, these are retirement accounts, not 'give your kid a huge inheritance account'.\"\" And the discussion continued from there. The age 70-1/2 was arbitrary. 70 happens to be the age for maximum Social Security benefits. But the average retirement age is 63. To make things more confusing, one can easily start taking IRA or 401(k) withdrawals at age 59-1/2, but for 401(k) as early as 55 if you separate from the job at 55 or later. One can also take withdrawals earlier from an IRA with tax, but no penalty using Sec 72(t) rules (such as 72(t)(2)(A)(iv) on Substantially Equal Periodic Payments). To add to the confusion, Roth IRA? No RMDs. Roth 401(k), RMDs once separated from service. Since the money has already been taxed, it's the tax on the growth the government loses. My advice to the reader would be to move the Roth 401(k) to a Roth IRA before 70-1/2. My advice to congress would be to change the code to have the same rules for both accounts. Whether one agrees that a certain rule is 'fair' to them or others is up to them. I think we can agree that the rules are remarkably complex, from origin to execution. And a moving target. You can see just from the history of this site how older questions are often revisited as code changes occur.\"", "title": "" }, { "docid": "202140", "text": "Is it worth saving HSA funds until retirement? Yes Are there pros and cons from a tax perspective? Mostly pros. This has all of the benefits of an IRA, but if you use it for medical expenses then you get to use the money tax free on the other side. Retirement seems to be the time you are most likely to need money for medical expenses. So why wouldn't you want to start saving tax free to cover those expenses? The cons are similar to other tax advantaged retirement accounts. If you withdraw before retirement time for non-medical purposes, you will pay penalties, but if you withdraw at retirement time, you will pay the same taxes you would pay on an IRA. I should note that I put my money where my mouth is and I max out my contribution to my HSA every year.", "title": "" }, { "docid": "587727", "text": "\"IRAs have huge tax-advantages. You'll pay taxes when you liquidate gold and silver. While volatile, \"\"the stock market has never produced a loss during any rolling 15-year period (1926-2009)\"\" [PDF]. This is perhaps the most convincing article for retirement accounts over at I Will Teach You To Be Rich. An IRA is just a container for your money and you may invest the money however you like (cash, stocks, funds, etc). A typical investment is the purchase of stocks, bonds, and/or funds containing either or both. Stocks may pay dividends and bonds pay yields. Transactions of these things trigger capital gains (or losses). This happens if you sell or if the fund manager sells pieces of the fund to buy something in its place (i.e. transactions happen without your decision and high turnover can result in huge capital gains). In a taxable account you will pay taxes on dividends and capital gains. In an IRA you don't ever pay taxes on dividends and capital gains. Over the life of the IRA (30+ years) this can be a huge ton of savings. A traditional IRA is funded with pre-tax money and you only pay tax on the withdrawal. Therefore you get more money upfront to invest and more money compounds into greater amounts faster. A Roth IRA you fund with after-tax dollars, but your withdrawals are tax free. Traditional versus Roth comparison calculator. Here are a bunch more IRA and 401k calculators. Take a look at the IRA tax savings for various amounts compared to the same money in a taxable account. Compounding over time will make you rich and there's your reason for starting young. Increases in the value of gold and silver will never touch compounded gains. So tax savings are a huge reason to stash your money in an IRA. You trade liquidity (having to wait until age 59.5) for a heck of a lot more money. Though isn't it nice to be assured that you will have money when you retire? If you aren't going to earn it then, you'll have to earn it now. If you are going to earn it now, you may as well put it in a place that earns you even more. A traditional IRA has penalties for withdrawing before retirement age. With a Roth you can withdraw the principal at anytime without penalty as long as the account has been open 5 years. A traditional IRA requires you take out a certain amount once you reach retirement. A Roth doesn't, which means you can leave money in the account to grow even more. A Roth can be passed on to a spouse after death, and after the spouse's death onto another beneficiary. more on IRA Required Minimum Distributions.\"", "title": "" }, { "docid": "94496", "text": "First of all, there are some differences between the retirement accounts that you mentioned regarding taxes. Traditional IRA and 401(k) accounts allow you to make pre-tax contributions, giving you an immediate tax deduction when you contribute. Roth IRA, Roth 401(k) are funded with after tax money, and a non-retirement account is, of course, also funded with after tax money. So if you are looking for the immediate tax deduction, this is a point in favor of the retirement accounts. Roth IRA & Roth 401(k) accounts allow the investment to grow tax-free, which means that the growth is not taxed, even when taking the investment out at retirement. With Traditional IRA and 401(k) accounts, you need to pay tax on the gains realized in the account when you withdraw the money, just as you do with a non-retirement account. This is a point in favor of the Roth retirement accounts. To answer your question about capital gains, yes, it is true that you do not have a capital gain until an investment is sold. So, discounting the contribution tax deductions of the retirement accounts, if you only bought individual stocks that never paid a dividend, and never sold them until retirement, you are correct that it really wouldn't matter if you had it in a regular brokerage account or in a traditional IRA. However, even people dedicated to buy-and-hold rarely actually buy only individual stocks and hold them for 30 years. There are several different circumstances that will generally happen in the time between now and when you want to withdraw the money in retirement that would be taxable events if you are not in a retirement account: If you sell an investment and buy a different one, the gains would be taxable. If you want to rebalance your holdings, this also involves selling a portion of your investments. For example, if you want to maintain an 80% stock/20% bond ratio, and your stock values have gone up to 90%, you might want to sell some stock and buy bonds. Or if you are getting closer to retirement, you might decide to go with a higher percentage of bonds. This would trigger capital gains. Inside a mutual fund, anytime the management sells investments inside the fund and realizes capital gains, these gains are passed on to the investors, and are taxable. (This happens more often with managed funds than index funds, but still happens occasionally with index funds.) Dividends earned by the investments are taxable. Any of these events in a non-retirement account would trigger taxes that need to be paid immediately, even if you don't withdraw a cent from your account.", "title": "" }, { "docid": "508219", "text": "\"Basically, the idea of an IRA is that the money is earned by you and would normally be taxed at the individual rate, but the government is allowing you to avoid paying the taxes on it now by instead putting it in the account. This \"\"tax deferral\"\" encourages retirement savings by reducing your current taxable income (providing a short-term \"\"carrot\"\"). However, the government will want their cut; specifically, when you begin withdrawing from that account, the principal which wasn't taxed when you put it in will be taxed at the current individual rate when you take it out. When you think about it, that's only fair; you didn't pay taxes on it when it came out of your paycheck, so you should pay that tax once you're withdrawing it to live on. Here's the rub; the interest is also taxed at the individual rate. At the time, that was a good thing; the capital gains rate in 1976 (when the Regular IRA was established) was 35%, the highest it's ever been. Now, that's not looking so good because the current cap gains rate is only 15%. However, these rates rise and fall, cap gains more than individual rates, and so by contributing to a Traditional IRA you simplify your tax bill; the principal and interest is taxed at the individual rate as if you were still making a paycheck. A Roth IRA is basically the government trying to get money now by giving up money later. You pay the marginal individual rate on the contributions as you earn them (it becomes a \"\"post-tax deduction\"\") but then that money is completely yours, and the kicker is that the government won't tax the interest on it if you don't withdraw it before retirement age. This makes Roths very attractive to retirement investors as a hedge against higher overall tax rates later in life. If you think that, for any reason, you'll be paying more taxes in 30 years than you would be paying for the same money now, you should be investing in a Roth. A normal (non-IRA) investment account, at first, seems to be the worst of both worlds; you pay individual tax on all earned wages that you invest, then capital gains on the money your investment earns (stock gains and dividends, bond interest, etc) whenever you cash out. However, a traditional account has the most flexibility; you can keep your money in and take your money out on a timeline you choose. This means you can react both to market moves AND to tax changes; when a conservative administration slashes tax rates on capital gains, you can cash out, pay that low rate on the money you made from your account, and then the money's yours to spend or to reinvest. You can, if you're market- and tax-savvy, use all three of these instruments to your overall advantage. When tax rates are high now, contribute to a traditional IRA, and then withdraw the money during your retirement in times where individual tax rates are low. When tax rates are low (like right now), max out your Roth contributions, and use that money after retirement when tax rates are high. Use a regular investment account as an overage to Roth contributions when taxes are low; contribute when the individual rate is low, then capitalize and reinvest during times when capital gains taxes are low (perhaps replacing a paycheck deduction in annual contributions to a Roth, or you can simply fold it back into the investment account). This isn't as good as a Roth but is better than a Traditional; by capitalizing at an advantageous time, you turn interest earned into principal invested and pay a low tax on it at that time to avoid a higher tax later. However, the market and the tax structure have to coincide to make ordinary investing pay off; you may have bought in in the early 90s, taking advantage of the lowest individual rates since the Great Depression. While now, capital gains taxes are the lowest they've ever been, if you cash out you may not be realizing much of a gain in the first place.\"", "title": "" }, { "docid": "298108", "text": "\"If you have maxed out your IRA contribution for 2017 already (and it all went into your Roth IRA), then, until the 2017 Tax Day in April 2018, you can remove any part of this contribution (and the earnings therefrom) from your Roth IRA without any tax consequences or penalties. If you discover in early 2018 that you are not eligible (or only partially eligible) to contribute to a Roth IRA, then of course you must remove all (or part) of your 2017 contributions (and the earnings therefrom) from your Roth IRA by the 2017 Tax Day in April 2018. Indeed, if you have filed for an extension of time to submit your 2017 tax return, then you have until the extended due date to make the withdrawal. As NathanL's answer points out, for 2017, you and withdraw and re-contribute \"\"as many times as you like\"\" though if you push this idea to excess with the same IRA custodian, the custodian may start charging fees. Note that IRS Publication 590b says in the Roth IRA section, Withdrawals of contributions by due date. If you withdraw contributions (including any net earnings on the contributions) by the due date of your return for the year in which you made the contribution, the contributions are treated as if you never made them. If you have an extension of time to file your return, you can withdraw the contributions and earnings by the extended due date. The withdrawal of contributions is tax free, but you must include the earnings on the contributions in income for the year in which you made the contributions. Now, if in the middle of all these transactions, you need to take a distribution from your Roth IRA during 2017 (say because you have a cash flow problem), then it makes a lot of sense to first withdraw all your 2017 contributions and the earnings therefrom. If more money is needed, than you can take a distribution from your Roth IRA. What the distribution consists of is described in great detail in Publication 590b and you might have to pay a tax penalty for a premature distribution depending on how much the distribution is. (The first dollars coming are assumed to be previous contributions in the order in which you made them and these are tax-free and penalty-free; after that the rollover and conversion amounts start to come out and are penalized if they have not spent 5 years in the IRA etc) But you can put the money back into your Roth IRA within 60 days and avoid penalties. Important Notes regarding rollover transactions:\"", "title": "" }, { "docid": "399564", "text": "Your best bets are a Roth IRA or traditional IRA. If you roll it to a Roth, you will have to pay taxes on the amount you roll over (unless it was a Roth 401k), however what is in the Roth will grow tax free and it will be tax free when you withdraw. With a traditional IRA, you won't owe taxes on the money now but will pay taxes when you withdraw. You won't be able to withdraw this money until 59 1/2 years of age without paying a penalty, the same goes for your current 401k. If you take the money (for mortgage, other investment, etc.) and don't roll it over to a qualified account, you will owe taxes on it plus a 10% penalty. So you will only get between 60% and 70% of its value.", "title": "" }, { "docid": "159197", "text": ">I could be wrong but you will still get tax at 10% This isn't true for Roths. If I put 5k (post tax of course) money into a Roth 401k or a Roth IRA I can withdraw that 5k whenever I want penalty and tax free. Now lets say that 5k has grown to 7k and I take out all 7k the first 5k is penalty and tax free but the extra 2k is taxed (with the extra 10% penalty added on). So as long as you don't touch any growth in your roth accounts you can withdraw the principal amount with the same consequences you would experience if you were to take money out of your checking account at your bank. Also money in and IRA does not have to be invested it could be in a liquid position. Now a pre tax retirement account doesn't have the same luxury. If I stick 5k into a traditional IRA and it grows to 7k and I pull that money out the entire ammount gets taxed AND penalized (even the principal amount is subject the 10% penalty). Now if you do a Roth conversion (pre-tax to post-tax retirment account conversion) the principal ammount (the amount you paid taxes on) is still subject to the 10% penalty for 5 years. After the 5 years you can withdraw the converted ammount tax and penalty free (well you already paid the taxes) it would just be the growth that is subject to the penalty.", "title": "" }, { "docid": "41417", "text": "\"1) Usually, the choice between Traditional vs. Roth is whether you believe that your tax rate will be higher or lower in the future than it is now. Your income is probably in the 25% bracket now. It's hard to say whether that should be considered \"\"high\"\" or \"\"low\"\". Some people advocate Roth only for 15% bracket; but your income would probably go into higher brackets in the future, so Roth may be preferable from this point of view. Roth IRA also has another advantage that the principal of contributions can be taken out at any time without tax or penalty, so it can serve as an emergency fund just as well as money in taxable accounts. Given that you may not have a lot of money saved up right now, this is useful. 2) In a sense, it's nice to have a mix of Traditional and Roth when you withdraw to hedge against uncertainty in future tax rates and have the option of choosing whichever one is advantageous to withdraw when you need to withdraw. That said, you will likely have many years of access to a 401k and high income in your future working years, in which you can contribute to a Traditional 401k (or if no access to 401k, then Traditional IRA), so a mix will almost certainly happen even if you go all Roth IRA now. 3) I think that depends on you, whether you are a hands-on or hands-off kind of investor.\"", "title": "" }, { "docid": "92442", "text": "Is there any benefit to investing in a Roth 401(k) plan, as opposed to a Roth IRA? They have separate contribution limits, so how much you contribute to one does not change the amount you can contribute to the other. Which is relevant to your question because you said the earnings on that account compounded over the next 40 years growing tax-free will be much higher than what I'd save on current taxes on a traditional 401(k). This is only true if you max out your contribution limits. If you start with the same amount of money and have the same marginal tax rate in both years, it doesn't matter which one you pick. Start with $10,000 to invest. With the traditional, you can invest all $10,000. With the Roth, you pay taxes on it and then invest it. Let's assume a tax rate of 25%. So invest $7500. Let's assume that you invest either amount long enough to double four times (forty years at 7% return after inflation is about right). So the traditional has $160,000 and the Roth has $120,000. Now you withdraw them. For simplicity's sake, we'll pretend it's all one year. It's probably over several years, but the math is easier in a single year. With the Roth, you have $120,000. With the traditional, you have to pay tax. Again, let's assume 25%. So that's $40,000, leaving you with $120,000 from the traditional. That is the same amount as the Roth! So it would make sense to If you can max out both, great. You do that for forty years and your retirement will be as financially secure as you can make it. If you can't max them out, the most important thing is the employer match. That's free money. Then you may prefer your Roth IRA to the 401k. Note that you can also roll over your Roth 401k to a Roth IRA. Then you can withdraw your contributions from the Roth IRA without penalty or additional tax. Alternate source. Beyond answering your question, I would still like to reiterate that Roth or traditional does not have a big effect on your investment unless you max them out or you have different tax rates now versus in retirement. It may change other things. For example, you can roll over a Roth 401k to a Roth IRA without paying taxes. And the Roth IRA will act like it was contributed directly. You have to check with your employer what their rollover rules are. They may allow it any time or only at employment separation (when you leave the job). If you do max out your Roth accounts, then they will perform better than the traditional accounts at the same nominal contribution. This is because they are tax free while your returns in the other accounts will have to pay taxes. But it doesn't matter until you hit the limits. Until then, you could just invest the tax savings of the traditional as well as the money you could invest in a Roth.", "title": "" }, { "docid": "482768", "text": "There are a few incorrect assumptions in your question but the TL;DR version is: All, or most, of the withdrawal is taxable income that is reported on Lines 15a (total distribution) and 15b (taxable amount) of Form 1040. None of the distribution is given special treatment as Qualified Dividends or Capital Gains regardless of what happened inside the IRA, and none of the distribution is subject to the 3.8% Net Investment Income Tax that some high-income people need to compute on Form 8960. If the withdrawal is not a Qualified Distribution, it will be subject to a 10% excise tax (tax penalty on premature withdrawal). Not all contributions to Traditional IRAs are deductible from income for the year for which the contribution was made. People with high income and/or coverage by a workplace retirement plan (pension plan, 401(k) plan, 403(b) plan, etc) cannot deduct any contributions that they choose to make to a Traditional IRA. Such people can always make a contribution (subject to them having compensation (earned income such as salary or wages, self-employment income, commissions on sales, etc), but they don't get a tax deduction for it (just as contributions to Roth IRAs are not deductible). Whether it is wise to make such nondeductible contributions to a Traditional IRA is a question on which reasonable people can hold different opinions. Be that as it may, nondeductible contributions to a Traditional IRA create (or add to) what is called the basis of an IRA. They are reported to the IRS on Form 8606 which is attached to the Federal Form 1040. Note that the IRA custodian or trustee is not told that the contributions are not deductible. Earnings on the basis accumulate tax-deferred within the IRA just as do the earnings on the deductible contributions. Now, when you make a withdrawal from your Traditional IRA, no matter which of your various IRA accounts you take the money from, part of the money is deemed to be taken from the basis (and is not subject to income tax) while the rest is pure taxable income. That is, none of the rest is eligible for the reduced taxation rates for Qualified Dividends or Capital Gains and since it does not count as investment income, it is not subject to the 3.8% Net Investment Tax of Form 8960 either. Computation of how much of your withdrawal is nontaxable basis and how much is taxable income is done on Form 8606. Note that you don't get to withdraw your entire basis until such time as when you close all your Traditional IRA accounts. How is all this reported? Well, your IRA custodian(s) will send you Form 1099-R reporting the total amount of the withdrawal, what income tax, if any, was withheld, etc. The custodian(s) don't know what your basis is, and so Box 2b will say that the taxable amount is not determined. You need to fill out Form 8606 to figure out what the taxable amount is, and then report the taxable amount on Line 15b of Form 1040. (The total withdrawal is reported on Line 15a which is not included in the AGI computations). Note that as far as the IRS is concerned, you have only one Traditional IRA. The A in IRA stands for Arrangement, not Account as most everybody thinks, and your Traditional IRA can invest in many different things, stocks, bonds, mutual funds, etc with different custodians if you choose, but your basis is in the IRA, not the specific investment that you made with your nondeductible contribution. That's why the total IRA contribution is limited, not the per-account contribution, and why you need to look that the total value of your IRA in determining the taxable portion, not the specific account(s) from which you withdrew the money. So, how much basis did you withdraw? Well, if you withdrew $W during 2016 and the total value of all your Traditional IRA accounts was $X at the end of 2016 and your total basis in your Traditional IRA is $B, then (assuming that you did not indulge in any Traditional-to-Roth rollovers for 2016), multiply W by B/(W+X) to get the amount of nontaxable basis in the withdrawal. B thus gets reduced for 2017 by amount of basis withdrawal. What if you never made a nondeductible contribution to your Traditional IRA, or you made some nondeductible contributions many years ago and have forgotten about them? Well, you could still fill out Form 8606 reporting a zero basis, but it will just tell you that your basis continues $0. Or, you could just enter the total amount of your withdrawal in Lines 15a and 15b, effectively saying that all of the withdrawal is taxable income to you. The IRS does not care if you choose to pay taxes on nontaxable income.", "title": "" }, { "docid": "214174", "text": "\"A Roth IRA is simply a tax-sheltered account that you deposit funds into, and then invest however you choose (within the limits of the firm you deposit the funds with). For example, you could open a Roth IRA account with Vanguard. You could then invest the $3000 by purchasing shares of VOO, which tracks the S&P 500 index and has a very low expense ratio (0.04 as of last time I checked). Fidelity has a similar option, or Schwab, or whatever brokerage firm you prefer. IRAs are basically just normal investment accounts, except they don't owe taxes until you withdraw them (and Roth don't even owe them then, though you paid taxes on the funds you deposit). They have some limitations regarding options trading and such, but if you're a novice investor just looking to do basic investments, you'll not notice. Then, your IRA would go up or down in value as the market went up or down in value. You do have some restrictions on when you can withdraw the funds; Roth IRA has fewer than a normal IRA, as you can withdraw the capital (the amount you deposited) without penalty, but the profits cannot be withdrawn until you're retirement age (I won't put an actual year, as I suspect that actual year will change by the time you're that old; but think 60s). The reason not to invest in an IRA is if you plan on using the money in the near future - even as an \"\"emergency fund\"\". You should have some money that is not invested aggressively, that is in something very safe and very accessible, for your emergency fund; and if you plan to buy a house or whatever with the funds, don't start an IRA. But if this is truly money you want to save for retirement, that's the best place to start. *Note, this is not investment advice, and you should do your own homework prior to making any investment. You can lose some or all of the value of your account while investing.\"", "title": "" }, { "docid": "461084", "text": "Why shouldn't I just keep my money in the savings account and earn the same amount (both accounts have the same APY in this case)? I will assume that you are transferring money from your savings account into a Traditional IRA and deducting the contribution from your income. While you may think that the money that is being transferred is yours already -- it is sitting in your savings account, for Pete's sake! -- you are deducting that amount in getting to your taxable income, and so you are effectively contributing it from current income and not paying taxes on the amount contributed. So, consider the same amount of money sitting in your savings account versus the same amount of money sitting in your Traditional IRA account. While you will earn the same amount of interest in both accounts, you will have to pay taxes each year on the interest earned in the savings account. You might choose, as most people do, to not take money out of the savings account to pay theses taxes but just pay them from ready cash/checking account/current income etc., or these taxes might just reduce the refund that you will getting from the IRS and your State income tax authority, but in either case, you have paid taxes on the interest earned in your non-IRA savings account, and of course, long ago, you also paid taxes on the original amount in the non-IRA savings account. So, if you take any money out of the non-IRA savings account, you don't pay any taxes on the amount withdrawn except possibly for the interest earned from January 1 till the date of withdrawal (which you are paying from ready cash). On the other hand, consider the Traditional IRA. The original deposit was not taxed in the sense that you got a deduction (reduced tax or increased refund) when you made the contribution. The annual interest earned was not taxed each year either. So when you make a qualified withdrawal (after age 59.5 or by meeting one of the other exceptions allowing withdrawal before age 59.5), you are taking money on which you have not paid any taxes at all, and the IRS wants its cut. The money withdrawn is taxable income to you. Furthermore, the money withdrawn is not eligible for any kind of favorable treatment such as having it count as qualified dividends or as long-term capital gains even if your IRA was invested in stocks and the money in the account is all qualified dividends or long-term capital gains. If you make an unqualified withdrawal, you owe a penalty (technically named an excise tax) in addition to income tax on the amount withdrawn. If you are investing in a Roth IRA, you will not be getting a deduction when you make the contribution, and qualified withdrawals are completely tax-free, and so the answer is completely different from the above.", "title": "" }, { "docid": "452870", "text": "\"The IRA contribution limit is a limit on the total amount you can contribute to all of your Roth and traditional IRAs. It's not a per-account limit. (See here and here.) Once you've hit the contribution limit on one account, you've hit it on all of them. Even so, supposing you had a reason with try to take money out of one of the accounts, the answer to your question is \"\"sort of\"\". The limit is a limit on your gross contributions, not your net contributions. It is possible to withdraw Roth contributions if you do so before the tax filing deadline for that year, but you must also withdraw (and pay taxes on) any earnings accured during the time the money was in the Roth (see here). In addition, doing this may not be as simple as just taking the money out of your account; you should probably ask your bank about it and let them know you're \"\"undoing\"\" the contribution, since they may otherwise still record the amount as a real contribution and the withdrawal as unqualified early withdrawal (subject to penalties, etc.).\"", "title": "" }, { "docid": "598378", "text": "\"For 401(k) and regular IRA, you pay income tax on withdrawals from the account. At a certain age, there is a \"\"required minimum distribution\"\". This is an amount you must withdraw from the account or you face penalties. I've also read about, but am not familiar with, mechanisms by which you can retire early and start taking withdrawals before the regular official retirement age. (These may or may not be legit, I didn't do any research on it.) A Roth IRA, which is not \"\"tax deferred\"\" and thus not technically covered by your question, there is no tax on withdrawals (assuming you are at retirement age) and no required minimum distribution. Something to watch out for on your accounts are fees that they charge for withdrawals. I was in a 401(k) once that had a $50 fee per-withdrawal. A monthly check from this account would eat your money! I paid the fee once, when I rolled it into an account at a brokerage after leaving the company.\"", "title": "" }, { "docid": "308150", "text": "\"If I understand correctly, the Traditional IRA, if you have 401k with an employer already, has the following features: Actually, #1 and #2 are characteristics of Roth IRAs, not Traditional IRAs. Only #3 is a characteristic of a Traditional IRA. Whether you have a 401(k) with your employer or not makes absolutely no difference in how your IRAs are taxed for the vast majority of people. (The rules for IRAs are different if you have a very high income, though). You're allowed to have and contribute to both kinds of accounts. (In fact, I personally have both). Traditional IRAs are tax deferred (not tax-free as people sometimes mistakenly call them - they're very different), meaning that you don't have to pay taxes on the contributions or profits you make inside the account (e.g. from dividends, interest, profits from stock you sell, etc.). Rather, you pay taxes on any money you withdraw. For Roth IRAs, the contributions are taxed, but you never have to pay taxes on the money inside the account again. That means that any money you get over and above the contributions (e.g. through interest, trading profits, dividends, etc.) are genuinely tax-free. Also, if you leave any of the money to people, they don't have to pay any taxes, either. Important point: There are no tax-free retirement accounts in the U.S. The distinction between different kinds of IRAs basically boils down to \"\"pay now or pay later.\"\" Many people make expensive mistakes in their retirement strategy by not understanding that point. Please note that this applies equally to Traditional and Roth 401(k)s as well. You can have Roth 401(k)s and Traditional 401(k)s just like you can have Roth IRAs and Traditional IRAs. The same terminology and logic applies to both kinds of accounts. As far as I know, there aren't major differences tax-wise between them, with two exceptions - you're allowed to contribute more money to a 401(k) per year, and you're allowed to have a 401(k) even if you have a high income. (By way of contrast, people with very high incomes generally aren't allowed to open IRAs). A primary advantage of a Traditional IRA is that you can (in theory, at least) afford to contribute more money to it due to the tax break you're getting. Also, you can defer taxes on any profits you make (e.g. through dividends or selling stock at a profit), so you can grow your money faster.\"", "title": "" }, { "docid": "461933", "text": "\"So you are paying taxes on your contributions regardless, the timing is just different. I am failing to see why would a person get an IRA, instead of just putting the same amount of money into a mutual fund (like Vanguard) or something like that. What am I missing? You are failing to consider the time value of money. Getting $1 now is more valuable to you than a promise to get $1 in a year, even though the nominal amount is the same. With a certain amount of principal now, you can invest it and it will (likely) grow into a bigger amount of money (principal + earnings) at a later time, and we can consider the two to have approximately equivalent value (the principal now has the same value as the principal + earnings later). With pre-tax money in Traditional IRA, the principal + earnings are taxed once at the time of withdrawal. Assuming the same flat rate of tax at contribution and withdrawal, this is equivalent to Roth IRA, where the principal is taxed at the time of contribution, because the principal now has the same value as the principal + earnings later, so the same rate of tax on the two have the same value of tax, even though when you look at nominal amounts, it might seem you are paying a lot less tax with Roth IRA (since the earnings are never \"\"taxed\"\"). With actual numbers, if we take a $1000 pre-tax contribution to Traditional IRA, it grows at 5% for 10 years, and a 25% flat rate tax, we are left with $1000 1.05^10 * 0.75 = $1221.67. With the same $1000 pre-tax contribution (so after 25% tax it's a $750 after-tax contribution) to a Roth IRA, growing at the same 5% for 10 years, and no tax at withdrawal, we are left with $1000 * 0.75 * 1.05^10 = $1221.67. You can see they are equivalent even though the nominal amount of tax is different (the lower amount of tax paid now is equivalent to the bigger amount of tax later). With a taxable investment which you will not buy and sell until you take it out, you contribute with after-tax money, and when you take it out, the \"\"earnings\"\" portion is subject to capital-gains tax. But remember that the principal + earnings later is equivalent to the principal now, which is already all taxed once, and if we tax the \"\"earnings\"\" portion later, that is effectively taxing a portion of the money again. Another way to look at it is the contribution is just like the Roth IRA, but the withdrawal is worse because you have to pay capital-gains tax instead of no tax. You can take the same numbers as for the Roth IRA, $1000 * 0.75 * 1.05^10 = $1221.67, but where the $1221.67 - $750 = $471.67 is \"\"earnings\"\" and is taxed again at, say, a 15% capital-gains rate, so you lose another $70.75 in tax and are left with $1150.92. You would need a capital-gains tax rate of 0% to match the advantage of the pre-tax Traditional IRA or Roth IRA. After-tax money in Traditional IRA has a similar problem -- the contribution is after tax, but after it grows into principal + earnings, the \"\"earnings\"\" part is taxed again, except it is worse than the capital-gains case because it is taxed as regular income. Like above, you can take the same numbers as for the Roth IRA, $1000 * 0.75 * 1.05^10 = $1221.67, but where the $471.67 \"\"earnings\"\" is taxed again at 25%, so you lose another $117.92 in tax and are left with $1103.75. So although the nominal amount of tax paid is the same as for pre-tax money in Traditional IRA, it ends up being a lot worse. (Everything I said above about pre-tax money in Traditional IRA, after-tax money in Traditional IRA, and Roth IRA, also applies to pre-tax money in Traditional 401(k), after-tax money in Traditional 401(k), and Roth 401(k), respectively.) Regarding the question you raise in the title of your question, why someone would get contribute to a Traditional IRA if they already have a 401(k), the answer is, mostly, they wouldn't. First, note that if you merely have a 401(k) account but neither you nor your employer contributes to it during the year, then that doesn't prevent you from deducting Traditional IRA contributions for that year, so basically you can contribute to one or the other; so if you only want to contribute below the IRA contribution limit, and don't need the bigger 401(k) contribution limit, and the IRA's investment options are more attractive to you than your 401(k)'s, then it might make sense for you to contribute to only Traditional IRA. If you or your employer is already contributing to your 401(k) during the year, then you cannot deduct your Traditional IRA contributions unless your income is very low, and if your income is really that low, you are in such a low tax bracket that Roth IRA may be more advantageous for you. If you make a Traditional IRA contribution but cannot deduct it, it is a non-deductible Traditional IRA contribution, i.e. it becomes after-tax money in a Traditional IRA, which as I showed in the section above has much worse tax situation in the long run because its earnings are pre-tax and thus taxed again. However, there is one good use for non-deductible Traditional IRA contributions, and that is as one step in a \"\"backdoor Roth IRA contribution\"\". Basically, there is an income limit for being able to make Roth IRA contributions, but there is no income limit for being able to make Traditional IRA contributions or for being able to convert money from Traditional IRA to Roth IRA. So what you can do is make a (non-deductible) Traditional IRA contribution, and then immediately convert it to Roth IRA, and if you did not previously have any pre-tax money in Traditional IRAs, this achieves the same as a regular Roth IRA contribution, with the same tax treatment, but you can do it at any income level.\"", "title": "" } ]
PLAIN-2517	Preventing Alzheimer’s Disease with Diet	[ { "docid": "MED-3417", "text": "The aim of this work is to assess the association between vasculogenic erectile dysfunction (ED) and coronary artery disease in men above the age of 40 y. The study included 40 patients above 40 y of age with vasculogenic ED of more than 3 months duration. A dynamic duplex study after intracavernosal injection of a bimix solution (60 mg papaverine + 2 mg phentolamine mesylate) was carried out using a color ultrasound machine. The patients underwent a stress ECG test, carried out on a motor-driven treadmill according to the 'Bruce Protocol'. A total of 12 patients were diagnosed with positive ischemic heart disease (IHD). Their mean peak systolic velocity (PSV) was PSV = 19.58 cm/s. In all, patients were diagnosed with negative IHD; their mean PSV was 36.21 cm/s. A statistically significant difference was observed between patients with positive IHD and patients with negative IHD regarding PSV (P = 0.003). The sensitivity of a PSV of less than 35 cm/s in predicting IHD was 50% with a specificity of 100%. Positive predictive value for abnormal stress ECG to predict a PSV of less than 35 cm/s was 100%. In conclusion, the PSV of cavernosal arteries is a reliable measure for predicting IHD in patients with vasculogenic ED. Patients with a PSV of less than 35 cm/s should be referred for cardiologic assessment as they carry a real risk of having silent IHD.", "title": "Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction." }, { "docid": "MED-3282", "text": "BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.", "title": "Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment." }, { "docid": "MED-1700", "text": "Objective To relate dietary fat types to cognitive change in healthy community-based elders. Methods Among 6,183 older participants in the Women’s Health Study, we related intake of major fatty acids (FAs) (saturated [SFA], mono-unsaturated [MUFA], total poly-unsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years post-dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariable-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake. Results Higher SFA intake was associated with worse global cognitive (p-linear-trend=0.008) and verbal memory (p-linear-trend=0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest vs. lowest SFA quintiles: the multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) was 1.64 (1.04,2.58) for global cognition and 1.65 (1.04,2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p-linear-trend<0.001) and verbal memory (p-linear-trend=0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31,0.88]) and verbal memory (0.56 [0.34,0.94]). Total fat, PUFA, and trans fat intakes were not associated with cognitive trajectory. Interpretation Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, while higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging.", "title": "Dietary fat types and 4-year cognitive change in community-dwelling older women" }, { "docid": "MED-4079", "text": "BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of a modified elimination diet and a supplemental medical food on clinical symptoms of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ), metallothionein mRNA expression, and urinary toxic element excretion. METHODS: Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a sequential design. During the initial 4-week Program A (control), participants consumed a modified US Department of Agriculture food pyramid diet and a rice protein powder supplement that provided basic macronutrient support. During the second 4-week Program B (intervention), participants consumed a modified elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to baseline, both programs showed trends toward lower mean FIQ total score, MSQ total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest headaches score. Compared to Program A, Program B resulted in a significant decrease (P< .05) in the FIQpain score and stiffness score. Participants also had better pain tolerance at five tender points during Program B than during Program A. Higher metallothionein mRNA expression was observed during Program B. An increase in creatinine-adjusted mercury excretion and suggestive increase in creatinine-adjusted arsenic excretion were noted when Program B was compared to baseline. Urinary mercury/arsenic concentrations were inversely associated with FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and efficacious botanically derived medical food treatment program for the amelioration of FM symptoms.", "title": "A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyalgia symptoms and promoted toxic-element deto..." }, { "docid": "MED-3439", "text": "Erectile dysfunction (ED) is common, affecting 40% of men over 40 years of age (so-called 40 over 40) and 1 in 3 men over 70 years of age. It is predominantly a vascular condition, often preceding a cardiovascular event by 3-5 years. ED is associated as a consequence with acute coronary syndromes and increased cardiovascular and all-cause mortality. Its early identification therefore offers a window of opportunity for cardiovascular risk reduction. ED has for many a devastating impact on a couple's relationship. Its treatment is often successful, maintaining quality of life in the middle aged and elderly. ED should always be queried as part of the ongoing health care worker and patient relationship - its early detection may prevent early death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Erectile dysfunction and coronary disease: evaluating the link." }, { "docid": "MED-3407", "text": "The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.", "title": "The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease" }, { "docid": "MED-4084", "text": "Experiences with food intake, diet manipulations and fast were registered in rheumatic patients. The study was a questionnaire-based survey in which 742 patients participated. It comprised 290 patients with rheumatoid arthritis, 51 patients with juvenile rheumatoid arthritis, 87 patients with ankylosing spondylitis, 51 patients with psoriatic arthropathy, 65 patients with primary fibromyalgia and 34 patients with osteoarthritis. One third of the patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthropathy reported aggravation of disease symptoms after intake of certain foods while 43% of the patients with juvenile rheumatoid arthritis and 42% of the patients with primary fibromyalgia stated the same. Twenty-six percent of the patients with juvenile rheumatoid arthritis and 23% of the patients with rheumatoid arthritis, ankylosing spondylitis and primary fibromyalgia had previously tried certain diets in the attempt to alleviate disease symptoms, whereas 13% of the patients with psoriatic arthropathy and 10% with osteoarthritis had tried diet therapy. Less pain and stiffness were reported by 46% of the patients and 36% reported reduced joint swelling. Similar beneficial effects of diet were also reported in other rheumatic disease groups. Fifteen percent of the patients with rheumatoid arthritis and ankylosing spondylitis had been through a fasting period. Less pain and stiffness were reported by 2/3 of the patients in both groups and half of the patients in both groups reported a reduced number of swollen joints.", "title": "Diet and disease symptoms in rheumatic diseases--results of a questionnaire based survey." }, { "docid": "MED-4581", "text": "We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.", "title": "Fruit and vegetable consumption and cognitive decline in aging women." }, { "docid": "MED-3274", "text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.", "title": "Olfactory detection of human bladder cancer by dogs: proof of principle study" }, { "docid": "MED-4789", "text": "Objectives To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design Six-month, randomized, controlled, clinical trial. Setting Veterans Affairs Puget Sound Health Care System clinical research unit. Participants Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42. Results Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. Conclusions This study provides support, using rigorous controlled methodology, for a potent nonpharma-cologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.", "title": "Effects of Aerobic Exercise on Mild Cognitive Impairment" }, { "docid": "MED-3276", "text": "Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension." }, { "docid": "MED-3427", "text": "Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "The link between erectile and cardiovascular health: the canary in the coal mine." }, { "docid": "MED-2664", "text": "In the 21st century, human aging will be one of the biggest challenges for most societies throughout the world. The decline in human fitness is a typical hallmark of the aging process. Aside from the cardiovascular system, the brain most often suffers significantly from the life-long impact of stressors, such as reactive oxygen and nitrogen species. Oxytosis, i.e. oxidative stress-induced cell death, has been identified to play a major role in the development and onset of chronic diseases. Foods, especially of plant origin, are rich in antioxidants and numerous in vivo data suggest that a diet rich in fruits and vegetables supports the maintenance of animal and human health. These beneficial effects also extend to the central nervous system, which, due to the presence of the blood-brain barrier, tightly controls the influx of metabolites and nutrients. In earlier studies the impact of antioxidant vitamins, such as alpha-tocopherol and ascorbic acid, on brain health has been of interest. Recently, the focus moved to assessing the potential of unsaturated fatty acids and secondary plant metabolites, particularly of polyphenols, to act as neuroprotectants. Considerable experimental evidence suggests that polyphenols and other plant-derived bioactivities affect animal and human brain function not only by directly lowering oxidative stress load but also by modulating various signal transduction pathways.", "title": "Plant foods and brain aging: a critical appraisal." }, { "docid": "MED-3432", "text": "Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.", "title": "Mediterranean diet improves erectile function in subjects with the metabolic syndrome." }, { "docid": "MED-2667", "text": "Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.", "title": "Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry ..." }, { "docid": "MED-3421", "text": "INTRODUCTION: Although penile blood flow (PBF) has been recommended as an additional diagnostic test in identifying erectile dysfunction (ED) patients at risk for latent cardiovascular disease, no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events (MACE). AIM: The aim of this study is to investigate whether severity of ED, PBF, and other factors related to a couple's relationship predict incident MACE. METHODS: A consecutive series of 1,687 patients was studied. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound) parameters were evaluated. MAIN OUTCOME MEASURES: Information on MACE was obtained through the City of Florence Registry Office. RESULTS: During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression analysis, after adjustment for age and Chronic Disease Score, showed that severe ED predicted MACE (hazard ratio [HR] 1.75; 95% confidence interval 1.10-2.78; P < 0.05). In addition, lower PBF, evaluated both in flaccid (before) and dynamic (after prostaglandin-E1 stimulation) conditions, was associated with an increased risk of MACE (HR = 2.67 [1.42-5.04] and 1.57 [1.01-2.47], respectively, for flaccid [<13 cm/second] and dynamic [<25 cm/second] peak systolic velocity; both P < 0.05). Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE. CONCLUSIONS: The investigation of male sexuality, and in particular PBF, and sexual desire, could provide insights not only into present cardiovascular status but also into prospective risk.", "title": "Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction." }, { "docid": "MED-4081", "text": "This article reviews the existing literature on fibromyalgia (FM) and diet, discusses the possible role of diet on central sensitization in FM, proposes a novel hypothesis of possible food-related contributors to central sensitization, and makes recommendations for future dietary research directions.", "title": "Potential dietary links to central sensitization in fibromyalgia: past reports and future directions." }, { "docid": "MED-4850", "text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.", "title": "Antioxidants in vegan diet and rheumatic disorders." }, { "docid": "MED-3424", "text": "The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.", "title": "Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of ..." }, { "docid": "MED-3141", "text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.", "title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome." }, { "docid": "MED-4582", "text": "Objective: Diet may be associated with risk of dementia and Alzheimer's disease (AD). We examined the association between fruit and vegetable consumption in midlife and risk for all types of dementia and AD. Methods: Participants were 3,779 members of the Swedish Twin Registry who completed a diet questionnaire approximately 30 years prior to cognitive screening and full clinical evaluation for dementia as part of the HARMONY study. Among the participants, 355 twins were diagnosed with dementia. Among these, 81 twin pairs were discordant for dementia (50 discordant for AD). Data were analyzed with logistic regression for the entire sample using generalized estimating equations to adjust for relatedness of twins, and with conditional logistic regression for the co-twin control design. Results: In fully-adjusted models, a medium or great proportion of fruits and vegetables in the diet, compared to no or small, was associated with a decreased risk of dementia and AD. This effect was observed among women and those with angina. Similar, but non-significant, odds ratios were found in the co-twin control analyses. Conclusion: Our findings suggest that higher fruit and vegetable consumption may reduce the risk of dementia, especially among women and those with angina pectoris in midlife.", "title": "Midlife Fruit and Vegetable Consumption and Risk of Dementia in Later Life in Swedish Twins" }, { "docid": "MED-2670", "text": "As the population of people in the United States over the age of 65 years continues to increase, so too will the incidence of age-related pathologies, including decreases in cognitive and motor function. In cases of severe deficits in memory or motor function, hospitalization and/or custodial care would be a likely outcome. This means that unless some way is found to reduce these age-related decrements in neuronal function, health care costs will continue to rise exponentially. Evidence is accumulating that consumption of blueberries may be one strategy to forestall or even reverse age-related neuronal deficits, as well as their subsequent behavioral manifestations, in order to increase healthy aging. Research suggests that the polyphenolic compounds found in blueberries exert their beneficial effects either through their ability to lower oxidative stress and inflammation or directly by altering the signaling involved in neuronal communication. These interventions, in turn, may protect against age-related deficits in cognitive and motor function. Appropriately, the US Department of Agriculture has figured prominently in these discoveries, through the efforts of two USDA researchers who worked for the department 100 years apart. Copyright © 2012 S. Karger AG, Basel.", "title": "Blueberries and neuronal aging." }, { "docid": "MED-3422", "text": "In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.", "title": "Mediterranean diet improves sexual function in women with the metabolic syndrome." }, { "docid": "MED-3438", "text": "Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection satisfactory for sexual performance. Evidence is accumulating to consider ED as a vascular disorder. Common risk factors for atherosclerosis are frequently found in association with ED, and ED is frequently reported in vascular syndromes, such as coronary artery disease (CAD), hypertension, cerebrovascular disease, peripheral arterial disease, and diabetes mellitus. Finally, similar early impairment of endothelium-dependent vasodilatation and late obstructive vascular changes has been reported in both ED and other vascular syndromes. Recently, we proposed a pathophysiologic mechanism to explain the link between ED and CAD called the artery size hypothesis. Given the systemic nature of atherosclerosis, all major vascular beds should be affected to the same extent. However, symptoms rarely become evident at the same time. This difference in rate of occurrence of different symptoms is proposed to be caused by the different size of the arteries supplying different vascular beds that allow a larger vessel to better tolerate the same amount of plaque compared with a smaller one. According to this hypothesis, because penile arteries are smaller in diameter than coronary arteries, patients with ED will seldom have concomitant symptoms of CAD, whereas patients with CAD will frequently complain of ED. Available clinical evidence appears to support this hypothesis.", "title": "The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease." }, { "docid": "MED-4583", "text": "Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.", "title": "Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study." }, { "docid": "MED-4088", "text": "The influence of a 3-week vegetarian diet and fasting on serum concentration of peroxides, lipids, apolipoproteins, and plasma fibrinogen was studied in ten middle-aged fibromyalgia/fibrositis patients (eight women, two men). Mean serum peroxide concentration (estimated as thiobarbituric acid reacting substances) was reduced from 3.60 +/- 0.14 to 2.82 +/- 0.15 umol/l (p = 0.01) and plasma fibrinogen from 3.33 +/- 0.25 to 2.74 +/- 0.15 g/l (p = 0.02). Serum total cholesterol fell from 6.61 +/- 0.50 to 4.83 +/- 0.35 mmol/l (p < 0.0001), apolipoprotein B from 1.77 +/- 0.14 to 1.31 +/- 0.11 g/l (p < 0.0001), and apolipoprotein A from 1.41 +/- 0.09 to 1.23 +/- 0.05 g/l (p = 0.03). High density lipoprotein cholesterol concentration also decreased somewhat (from 1.26 +/- 0.09 to 1.07 +/- 0.04 mmol/l, p = 0.03) An atherogenic index, reflecting the balance between low and high density lipoproteins, was reduced by 31% (from 5.74 +/- 0.79 to 3.97 +/- 0.60, p = 0.02). The results suggest that vegetarian diet/fasting may have a beneficial influence on the concentration of serum peroxides and plasma fibrinogen concentration, and on the serum level of several lipoprotein-related coronary risk factors.", "title": "Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet." }, { "docid": "MED-3429", "text": "Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction." }, { "docid": "MED-1703", "text": "There are currently approximately 33.9 million individuals with Alzheimer's disease (AD) worldwide, and prevalence is expected to triple over the next 40 years. The goal of this review was to summarize the evidence regarding seven potentially modifiable AD risk factors: diabetes, mid-life hypertension, mid-life obesity, smoking, depression, low educational attainment and physical inactivity. In addition, we projected the impact of risk factor reduction on AD prevalence by calculating population attributable risks (PARs, the percent of cases attributable to a given factor) and the number of AD cases that could potentially be prevented by 10% and 25% risk factor reductions worldwide and in the US. Together, these factors contributed to up to half of AD cases globally (17.2 million) and in the US (2.9 million). A 10%–25% reduction in all seven risk factors could potentially prevent as many as 1.1–3.0 million cases worldwide and 184,000–492,000 cases in the US.", "title": "The Projected Impact of Risk Factor Reduction on Alzheimer's Disease Prevalence" }, { "docid": "MED-3271", "text": "Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.", "title": "Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?" }, { "docid": "MED-3275", "text": "In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.", "title": "The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture" }, { "docid": "MED-3281", "text": "INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.", "title": "Targeting methionine auxotrophy in cancer: discovery & exploration." }, { "docid": "MED-3426", "text": "OBJECTIVES: The purpose of our study was to assess the prevalence and extent of coronary artery atherosclerosis in asymptomatic patients with vascular erectile dysfunction (ED). BACKGROUND: An association between ED and ischemic heart disease has been suggested, but it is unknown if it represents a marker of subclinical coronary atherosclerosis. METHODS: We studied 70 consecutive patients with vascular ED, evaluated by penile Doppler, and 73 control subjects with no history of coronary artery disease. We measured traditional coronary risk factors, circulating levels of C-reactive protein (CRP), endothelial function by ultrasound of brachial artery, and coronary artery calcification by multi-slice computed tomography. RESULTS: The patients and the control group were similar for age, race, and coronary risk score. Patients with ED had significantly higher high-sensitivity C-reactive protein levels (2.62 vs. 1.03 mg/l, p < 0.001). Flow-mediated dilation of the brachial artery was more impaired in patients with ED than in controls (2.36 vs. 3.92, p < 0.001). Coronary artery calcification was more frequent in individuals with ED than in control subjects (p = 0.01). Multiple logistic regression analysis showed that patients with ED had an overall odds ratio of 3.68 for having calcium score above the 75th percentile, compared to the controls. CONCLUSIONS: Coronary atherosclerosis is more severe in patients with vascular ED; ED predicts the presence and extent of subclinical atherosclerosis independent of traditional risk factors for cardiovascular disease. Thus, ED may be considered an additional, early warning sign of coronary atherosclerosis.", "title": "Subclinical coronary artery atherosclerosis in patients with erectile dysfunction." }, { "docid": "MED-3143", "text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.", "title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial." }, { "docid": "MED-3139", "text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.", "title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women" }, { "docid": "MED-3280", "text": "Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.", "title": "Methionine dependency and cancer treatment." }, { "docid": "MED-2669", "text": "Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with CVD, and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In addition, preliminary animal data have indicated improvement in memory and motor function with grape juice supplementation, suggesting potential for cognitive benefit in ageing humans. In this initial investigation of neurocognitive effects, we enrolled twelve older adults with memory decline but not dementia in a randomised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. We observed significant improvement in a measure of verbal learning and non-significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with early memory decline and establish a basis for more comprehensive investigations to evaluate potential benefit and assess mechanisms of action.", "title": "Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment." }, { "docid": "MED-3428", "text": "OBJECTIVES: The aim of this study was to assess erectile dysfunction prevalence, time of onset and association with risk factors in patients with acute chest pain and angiographically documented coronary artery disease. METHODS: 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease were assessed using a semi-structured interview investigating their medical and sexual histories, the International Index of Erectile Function and other instruments. RESULTS: Patient mean age was 62.5+/-8 years (range 33-86 years). Mean duration of symptoms or signs of myocardial ischaemia prior to enrollment in the study was 49 months (range 1-200). Coronary angiography showed 1-, 2- and 3-vessel disease in 98 (32.6%), 88 (29.3%) and 114 (38%) patients, respectively. The prevalence of ED among all patients was 49% (147/300). Erectile dysfunction was scored as mild, mild to moderate, moderate and severe in 21 (14%), 31 (21%), 20 (14%), and 75 (51%) of patients, respectively. There was no significant difference between patients with ED (n=147) or without ED (n=153) as far as clinical and angiographic characteristics were concerned. In the 147 patients with co-existing ED and CAD, ED symptoms were reported as having become clinically evident prior to CAD symptoms by 99/147 (67%) patients. The mean time interval between the onset of ED and CAD was 38.8 months (range 1-168). There was no significant difference in terms of risk factor distribution and clinical and angiographic characteristics between patients with the onset of ED before vs. after CAD diagnosis. Interestingly, all patients with type I diabetes and ED actually developed sexual dysfunction before CAD onset (p<0.001). CONCLUSIONS: Our study suggests that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases. Future studies including a control group of patients with coronary artery disease and normal erectile function are required in order to verify whether erectile dysfunction may be considered a real predictor of ischemic heart disease.", "title": "Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographic..." }, { "docid": "MED-4790", "text": "It is a pleasure and an honor to contribute a paper to a special issue of the Journal of the American College of Nutrition honoring Stanley Wallach and Pearl Small. In this brief review I advance the hypothesis that copper toxicity is the major cause of the epidemic of mild cognitive impairment and Alzheimer's disease engulfing our aging population. This epidemic is recent, exploding in the last 50-60 years. The disease was virtually unknown 100 years ago. And it involves only developed countries that use copper plumbing. Something in our environment associated with development is poisoning the minds of our aged. The epidemic is associated with the use of copper plumbing, and the taking of copper in multi-mineral supplements. Food copper (organic copper) is processed by the liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly. This copper is potentially toxic because it may penetrate the blood/brain barrier. I review a web of animal and human data that tightens the noose around the hypothesis that copper toxicity is causing the epidemic of Alzeimer's disease and loss of cognition in our aging population.", "title": "The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease." }, { "docid": "MED-3435", "text": "INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the \"Longitudinal Health Insurance Database.\" The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.", "title": "Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study." }, { "docid": "MED-4085", "text": "The effect of a strict, low-salt, uncooked vegan diet rich in lactobacteria on symptoms in 18 fibromyalgia patients during and after a 3-month intervention period in an open, non-randomized controlled study was evaluated. As control 15 patients continued their omnivorous diet. The groups did not differ significantly from each other in the beginning of the study in any other parameters except in pain and urine sodium. The results revealed significant improvements in Visual analogue scale of pain (VAS) (p=0.005), joint stiffness (p=0.001), quality of sleep (p=0.0001), Health assessment questionnaire (HAQ) (p=0.031), General health questionnaire (GHQ) (p=0.021), and a rheumatologist's own questionnaire (p=0.038). The majority of patients were overweight to some extent at the beginning of the study and shifting to a vegan food caused a significant reduction in body mass index (BMI) (p=0.0001). Total serum cholesterol showed a statistically significant lowering (p=0.003). Urine sodium dropped to 1/3 of the beginning values (p=0.0001) indicating good diet compliance. It can be concluded that vegan diet had beneficial effects on fibromyalgia symptoms at least in the short run.", "title": "Vegan diet alleviates fibromyalgia symptoms." }, { "docid": "MED-4080", "text": "Background Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome. Methods During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients. Results We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora. Conclusion Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.", "title": "Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study" }, { "docid": "MED-3270", "text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.", "title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals." }, { "docid": "MED-3437", "text": "INTRODUCTION: The use of the penile peak systolic velocity (PSV) measured in the flaccid state during penile color Doppler ultrasound (PCDU) examination has been questioned without substantial evidence. AIM: To assess the validity of PSV measured in the flaccid state during PCDU, in patients consulting for erectile dysfunction (ED). METHODS: A consecutive series of 1,346 (mean age 55.0 +/- 12.0 years) male patients was studied. MAIN OUTCOMES MEASURES: All patients underwent PCDU performed both in the flaccid state and dynamic (after prostaglandin E1 stimulation) conditions. A subset of 20 subjects with uncomplicated type 2 diabetes underwent diagnostic testing for silent coronary heart disease by means of adenosine stress myocardial perfusion scintigraphy (SPECT). In these subjects penile arterial flow was simultaneously assessed by PCDU before and after systemic adenosine administration. RESULTS: Flaccid PSV showed a significant (r = 0.513, P < 0.0001) correlation with dynamic PSV. Receiver operating characteristic (ROC) curve analysis demonstrated that when a threshold of 13 cm/seconds was chosen, flaccid PSV was predictive for dynamic PSV < 25 and <35 cm/seconds with an accuracy of 89% and 82%, respectively. Among the subset of patients who underwent SPECT, an impaired coronary flow reserve (ICFR) occurred in nine cases (45%). When the same threshold of <13 cm/seconds was chosen, PSV before SPECT was predictive of ICFR with an accuracy of 80% (area under the ROC curve = 0.798 +/- 0.10; P < 0.05). After adjustment for confounders, anxiety symptoms were related to dynamic PSV (Adj. r = -0.154, P < 0.05) but not to flaccid PSV. CONCLUSIONS: Our results show that flow in the cavernosal arteries can be routinely evaluated by PCDU in the flaccid state. Performing PCDU only in the flaccid state allows identifying subjects with pathological dynamic PSV with accuracy higher than 80%. Furthermore, our preliminary data suggest that the same examination could identify diabetic subjects with ICFR with an accuracy of 80%.", "title": "Penile doppler ultrasound in patients with erectile dysfunction (ED): role of peak systolic velocity measured in the flaccid state in predicting ar..." }, { "docid": "MED-3272", "text": "Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.", "title": "Colorectal cancer screening with odour material by canine scent detection" }, { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-3136", "text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.", "title": "Influence of frequent and long-term bean consumption on colonic function and fermentation." }, { "docid": "MED-3137", "text": "A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.", "title": "Americans Do Not Meet Federal Dietary Recommendations" }, { "docid": "MED-3277", "text": "Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.", "title": "Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture." }, { "docid": "MED-3420", "text": "Introduction Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms and often co-occur. Yet it is not known whether ED provides an early warning for increased CVD or other causes of mortality. Aim We sought to examine the association of ED with all-cause and cause-specific mortality. Methods Prospective, population-based study of 1,709 men (of 3,258 eligible) aged 40–70 years. ED was measured by self-report. Subjects were followed for a mean of 15 years. Hazard ratios (HR) were calculated using the Cox proportional hazards regression model. Main outcome measures Mortality due to all causes, CVD, malignant neoplasms, and other causes. Results Of 1,709 men, 1,284 survived to the end of 2004 and had complete ED and age data. Of 403 men who died, 371 had complete data. After adjustment for age, body mass index, alcohol consumption, physical activity, cigarette smoking, self-assessed health, and self-reported heart disease, hypertension, and diabetes, ED was associated with HRs of 1.26 [95% confidence interval (CI), 1.01–1.57] for all-cause mortality and 1.43 (95% CI, 1.00–2.05) for CVD mortality. The HR for CVD mortality associated with ED is of comparable magnitude to HRs of some conventional CVD risk factors. Conclusions These findings demonstrate that ED is significantly associated with increased all-cause mortality, primarily through its association with CVD mortality.", "title": "Erectile Dysfunction and Mortality" }, { "docid": "MED-1699", "text": "BACKGROUND: Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia. METHODS: We conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January 2012. Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia. RESULTS: Twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent. CONCLUSIONS: Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia.", "title": "Mediterranean diet, cognitive function, and dementia: a systematic review." }, { "docid": "MED-3433", "text": "OBJECTIVES: Our goal was to evaluate the association between erectile dysfunction (ED) and risk of cardiovascular disease (CVD) and all-cause mortality by conducting a meta-analysis of prospective cohort studies. BACKGROUND: Observational studies suggest an association between ED and the incidence of CVD. However, whether ED is an independent risk factor of CVD remains controversial. METHODS: The PubMed database was searched through January 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twelve prospective cohort studies involving 36,744 participants were included in the meta-analysis. The overall combined relative risks for men with ED compared with the reference group were 1.48 (95% confidence interval [CI]: 1.25 to 1.74) for CVD, 1.46 (95% CI: 1.31 to 1.63) for coronary heart disease, 1.35 (95% CI: 1.19 to 1.54) for stroke, and 1.19 (95% CI: 1.05 to 1.34) for all-cause mortality. Sensitivity analysis restricted to studies with control for conventional cardiovascular risk factors yielded similar results. No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that ED significantly increases the risk of CVD, coronary heart disease, stroke, and all-cause mortality, and the increase is probably independent of conventional cardiovascular risk factors. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies." }, { "docid": "MED-3140", "text": "To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.", "title": "Legumes: the most important dietary predictor of survival in older people of different ethnicities." }, { "docid": "MED-3278", "text": "Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.", "title": "Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening" }, { "docid": "MED-3425", "text": "OBJECTIVES: We examined whether common coronary heart disease (CHD) risk factors measured in mid-life predict erectile dysfunction (ED) 25 years later. BACKGROUND: Retrospective and cross-sectional studies have suggested that ED is associated with classic CHD risk factors, but few prospective studies have studied these associations. METHODS: In this prospective study of community-dwelling men age 30 to 69 years, seven classic CHD risk factors (age, smoking, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, and obesity) were assessed from 1972 to 1974. In 1998, after an average follow-up of 25 years, surviving male participants were asked to complete the International Index of Erectile Function (IIEF-5), which allows stratification of ED into five groups. RESULTS: Sixty-eight percent of the surviving men returned, and 60% completed the IIEF-5 questionnaire. Respondents had more favorable levels of all heart disease risk factors at baseline than non-respondents. At baseline, the average age of the 570 ED study participants was 46 years; at follow-up, their average age was 72 years. Mean age, body mass index, cholesterol, and triglycerides were each significantly associated with an increased risk of ED. Cigarette smoking was marginally more common in those with severe/complete ED, as compared with those without ED. Blood pressure and fasting blood glucose were not significantly associated with ED, likely due to selective mortality. CONCLUSIONS: Improving CHD risk factors in mid-life may decrease the risk of ED as well as CHD. Erectile dysfunction should be included as an outcome in clinical trials of lipid-lowering agents and lifestyle modifications.", "title": "Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study." }, { "docid": "MED-3440", "text": "INTRODUCTION: It is unclear whether men with erectile dysfunction (ED) ultimately die of cardiovascular (CV) causes. AIM: This study examined the causes of death in men with ED and their risk of CV death. METHODS: Based on statutory death registrations and hospital morbidity data, the risk of CV death in men with ED in a linked-data study was assessed against the CV mortality risk in a reference male population. MAIN OUTCOME MEASURES: Deaths from CV causes as proportions of all deaths. Age-specific rate, mortality rate ratio (MRR), standardized mortality rate ratio (SMRR), and adjusted hazard ratio (HR). RESULTS: CV mortality was 4.0%. Compared with the reference population, the risk of CV death was higher in men with ED (SMRR 2.2; 95% confidence interval [CI] 1.6, 3.0). Risk of CV mortality was higher in men with CV disease prior to ED (adjusted HR 1.7; 95% CI 1.1, 2.6) or with history of hospital admissions for CV events (adjusted HR 2.2; 95% CI 1.3, 3.8), compared with those without the respective history. MRR was significantly increased in the 40-69 years age group (MRR 4.1; 95% CI 3.2, 5.2). The median time interval between manifestation of ED and CV death was 10.0 years. A greater proportion of deaths from oncological than from CV causes (25.0% vs. 10.8%) occurred within the first 5 years of the manifestation of ED. CONCLUSIONS: Although the risk of CV mortality is greater in men with ED, almost as many men die of oncological as of CV causes, with a higher proportion of oncological deaths occurring sooner subsequent to the first manifestation of ED. © 2011 International Society for Sexual Medicine.", "title": "Cardiovascular mortality in men with erectile dysfunction: increased risk but not inevitable." }, { "docid": "MED-2663", "text": "Today, tens of millions of elderly individuals worldwide suffer from dementia. While the pathogenesis of dementia is complex and incompletely understood, it may be, at least to a certain extent, the consequence of systemic vascular pathology. The metabolic syndrome and its individual components induce a proinflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic. Associations have been established between the metabolic syndrome, its constituents and dementia. A relationship has also been observed between certain dietary factors, such as constituents of the 'Mediterranean diet', and the metabolic syndrome; similar associations have been noted between these dietary factors and dementia. Fruit juices and extracts are under investigation as treatments for cognitive impairment. Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared. The benefits of fruit products are thought to be a result of its polyphenol content. A grape polyphenol found in grapes, resveratrol, now being studied in humans, and one in grapes and blueberries, pterostilbene, have been found to improve cognition in rodents. In the design of future human trials, one ought to consider the poor bioavailability of these products, the possible need to initiate the experimental therapy long before the onset of symptoms, and currently limited knowledge about the appropriate form (e.g. juice, powder or individual polyphenol) of treatment.", "title": "A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders." }, { "docid": "MED-3434", "text": "INTRODUCTION: Although epidemiological evidence seems to support a role for lifestyle factors in the pathogenesis of erectile dysfunction (ED), limited data are available suggesting that dietary changes may improve ED. AIM: To provide an update on clinical evidence regarding the role of dietary factors in ED. METHODS: A systematic literature search was performed using MEDLINE and other database (EMBASE, SCOPUS) with MeSH terms and keywords for \"erectile dysfunction\", \"diet\", \"dietary patterns\", \"Mediterranean diet\", and \"lifestyle\". MAIN OUTCOME MEASURES: To examine the data relating to erectile dysfunction with dietary factors, its relationship and the impact of dietary treatment. RESULTS: Only few studies assessed the role or the effect of diet on ED. A dietary pattern which is high in fruit, vegetables, nuts, whole grains, and fish but low in red and processed meat and refined grains is more represented in subjects without ED. Mediterranean diet has been proposed as a healthy dietary pattern based on evidence that greater adherence to this diet is associated with lower all-cause and disease-specific survival. In type 2 diabetic men, those with the highest adherence to the Mediterranean diet had the lowest prevalence of ED and were more likely to be sexually active. In clinical trials, Mediterranean diet was more effective than a control diet in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome. CONCLUSION: The adoption of a Mediterranean diet may be associated with an improvement of erectile dysfunction.", "title": "Dietary factors, Mediterranean diet and erectile dysfunction." }, { "docid": "MED-3436", "text": "Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.", "title": "How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors." }, { "docid": "MED-4087", "text": "Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.", "title": "Fibromyalgia and nutrition, what do we know?" }, { "docid": "MED-3279", "text": "Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.", "title": "Chitin synthesis and degradation as targets for pesticide action." }, { "docid": "MED-3283", "text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.", "title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..." }, { "docid": "MED-2668", "text": "Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline.", "title": "Concord grape juice supplementation and neurocognitive function in human aging." }, { "docid": "MED-1702", "text": "Background We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. Objectives To examine the association between MeDi and mortality in patients with AD. Methods A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. Results Eighty-five patients with AD (44%) died during the course of 4.4 (±3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence fertile, those at the middle fertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years’ longer survival), whereas subjects at the highest fertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years’ longer survival; p for trend = 0.003). Conclusion Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose–response effect.", "title": "Mediterranean diet and Alzheimer disease mortality" }, { "docid": "MED-2665", "text": "Objective Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women. Methods Beginning in 1980, a semi-quantitative food frequency questionnaire was administered every four years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at two-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariable-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes. Results Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (e.g., for a global score averaging all six cognitive tests, for blueberries: p-trend=0.014 and mean difference=0.04 [95% CI=0.01, 0.07] comparing extreme categories of intake; for strawberries: p-trend= 0.022 and mean difference=0.03 [95% CI=0.00, 0.06] comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we find for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends= 0.015 and 0.053, respectively, for the global score). Interpretation Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.", "title": "Dietary intake of berries and flavonoids in relation to cognitive decline" }, { "docid": "MED-3142", "text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.", "title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China." }, { "docid": "MED-1701", "text": "Cardiovascular disease prevention is of high priority in developed countries. Healthy eating habits including the regular intake of an antithrombotic diet (fruit and vegetables) may contribute to prevention. Platelet function is a critical factor in arterial thrombosis and the effect strawberries have is still unclear. Therefore, the aim of this study was to systematically examine the action of strawberries in preventing platelet activation and thrombus formation. Strawberry extract concentration-dependently (0.1-1 mg/ml) inhibited platelet aggregation induced by ADP and arachidonic acid. At the same concentrations as strawberry inhibits platelet aggregation, it significantly decreased sP-selectin, sCD40L, RANTES, and IL-1β levels. The strawberry may exert significant protective effects on thromboembolic-related disorders by inhibiting platelet aggregation. Also, this suggests that antithrombotic activity may have novel anti-inflammatory effects.", "title": "Strawberry extract presents antiplatelet activity by inhibition of inflammatory mediator of atherosclerosis (sP-selectin, sCD40L, RANTES, and IL-1β..." }, { "docid": "MED-3430", "text": "BACKGROUND: Erectile dysfunction (ED) shares similar modifiable risks factors with coronary artery disease (CAD). Lifestyle modification that targets CAD risk factors may also lead to improvement in ED. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of lifestyle interventions and pharmacotherapy for cardiovascular (CV) risk factors on the severity of ED. METHODS: A comprehensive search of multiple electronic databases through August 2010 was conducted using predefined criteria. We included randomized controlled clinical trials with follow-up of at least 6 weeks of lifestyle modification intervention or pharmacotherapy for CV risk factor reduction. Studies were selected by 2 independent reviewers. The main outcome measure of the study is the weighted mean differences in the International Index of Erectile Dysfunction (IIEF-5) score with 95% confidence intervals (CIs) using a random effects model. RESULTS: A total of 740 participants from 6 clinical trials in 4 countries were identified. Lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in sexual function (IIEF-5 score): weighted mean difference, 2.66 (95% CI, 1.86-3.47). If the trials with statin intervention (n = 143) are excluded, the remaining 4 trials of lifestyle modification interventions (n = 597) demonstrate statistically significant improvement in sexual function: weighted mean difference, 2.40 (95% CI, 1.19-3.61). CONCLUSION: The results of our study further strengthen the evidence that lifestyle modification and pharmacotherapy for CV risk factors are effective in improving sexual function in men with ED.", "title": "The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis." }, { "docid": "MED-4860", "text": "The prevalence of dementia is increasing with expansion of the older adult population. In the absence of effective therapy, preventive approaches are essential to address this public health problem. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with increased neuronal signaling in brain centers mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration. We investigated the effects of daily consumption of wild blueberry juice in a sample of nine older adults with early memory changes. At 12 weeks, we observed improved paired associate learning (p = 0.009) and word list recall (p = 0.04). In addition, there were trends suggesting reduced depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10). We also compared the memory performances of the blueberry subjects with a demographically-matched sample who consumed a berry placebo beverage in a companion trial of identical design and observed comparable results for paired associate learning. The findings of this preliminary study suggest that moderate-term blueberry supplementation can confer neurocognitive benefit and establish a basis for more comprehensive human trials to study preventive potential and neuronal mechanisms.", "title": "Blueberry Supplementation Improves Memory in Older Adults" }, { "docid": "MED-3423", "text": "INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.", "title": "Adherence to Mediterranean diet and sexual function in women with type 2 diabetes." }, { "docid": "MED-3273", "text": "Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.", "title": "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy." } ]	[ { "docid": "MED-1705", "text": "Despite an archive of over 73,000 research papers published in the last two decades on the subject of Alzheimer's disease (AD), little clinical progress has been made relative to how people get sporadic AD and what can be done to help them avoid it. This review spotlights strategic steps that could be a turning point in the dramatic lowering of Alzheimer prevalence. The main strategy includes application of four pillars of prevention: 1) early identification of AD vascular risk factors; 2) early detection of AD vascular risk factors; 3) early intervention of AD vascular risk factors based on evidence-based medical decisions; 4) patient follow-up to assess and modify interventions as needed. Tandem to these four pillars of prevention, a proactive lifestyle consisting of a healthy diet coupled to physical and mental activity should be applied as part of any therapeutic intervention. We are persuaded by mounting and compelling evidence that AD is a multifactorial disorder kindled by vascular risk factors that generate chronic brain hypoperfusion (CBH) during advanced aging. A pathobiological cascade of biochemical events in the presence of CBH that leads to oxidative stress and neurodegeneration appears to involve multiple biofactors including micronutrients, trace metals, lipids, and pro-oxidants, as reviewed in this special issue of BioFactors. Modulation of these biofactors may help prevent or control incipient AD. © 2012 International Union of Biochemistry and Molecular Biology, Inc. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "A turning point for Alzheimer's disease?" }, { "docid": "MED-983", "text": "BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. METHODS: A stochastic, multistate model was used in conjunction with United Nations worldwide population forecasts and data from epidemiological studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will quadruple, by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care, equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050, with nearly the entire decline attributable to decreases in persons needing a high level of care. CONCLUSIONS: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in the onset and progression of Alzheimer's disease can significantly reduce the global burden of this disease.", "title": "Forecasting the global burden of Alzheimer's disease." }, { "docid": "MED-1408", "text": "OBJECTIVE: This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease. METHODS: Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence. RESULTS: Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age. INTERPRETATION: Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies. © 2013 American Neurological Association.", "title": "Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis." }, { "docid": "MED-1504", "text": "BACKGROUND: Numerous studies have investigated risk factors for Alzheimer disease (AD). However, at a recent National Institutes of Health State-of-the-Science Conference, an independent panel found insufficient evidence to support the association of any modifiable factor with risk of cognitive decline or AD. OBJECTIVE: To present key findings for selected factors and AD risk that led the panel to their conclusion. DATA SOURCES: An evidence report was commissioned by the Agency for Healthcare Research and Quality. It included English-language publications in MEDLINE and the Cochrane Database of Systematic Reviews from 1984 through October 27, 2009. Expert presentations and public discussions were considered. STUDY SELECTION: Study inclusion criteria for the evidence report were participants aged 50 years and older from general populations in developed countries; minimum sample sizes of 300 for cohort studies and 50 for randomized controlled trials; at least 2 years between exposure and outcome assessment; and use of well-accepted diagnostic criteria for AD. DATA EXTRACTION: Included studies were evaluated for eligibility and data were abstracted. Quality of overall evidence for each factor was summarized as low, moderate, or high. DATA SYNTHESIS: Diabetes mellitus, hyperlipidemia in midlife, and current tobacco use were associated with increased risk of AD, and Mediterranean-type diet, folic acid intake, low or moderate alcohol intake, cognitive activities, and physical activity were associated with decreased risk. The quality of evidence was low for all of these associations. CONCLUSION: Currently, insufficient evidence exists to draw firm conclusions on the association of any modifiable factors with risk of AD.", "title": "Risk factors and preventive interventions for Alzheimer disease: state of the science." }, { "docid": "MED-1704", "text": "The dramatic rising incidence and costs of Alzheimer's disease (AD) require that research efforts and funding be primarily directed on either finding a cure or applying preventive measures to curb this disorder. A cure for AD appears unlikely when significant cognitive loss has occurred because the neuronal networks that controlled the perturbed cognitive abilities are either dead or irreversibly damaged and replacing them, even if it were technically possible, would not reconstruct the intellectual identity of the host. Prevention of risk factors to sporadic AD is a more realistic stratagem and treatment, when indicated, ideally should begin in cognitively intact individuals as part of a mass screening effort. Prevention of modifiable risk factors to AD is cost-effective because it reduces hospice or hospital stay, repeated doctor visits, and long-term care. Presently, neurocognitive and neuroimaging tests are used with partial success in identifying persons at higher risk of AD but these tests can not pinpoint either a cause or a specific intervention that could attenuate disease progress. We previously proposed that carotid artery ultrasound +echocardiography together with ankle-brachail index (CAUSE+ABI) as mass screening tests in asymptomatic persons could detect not only cardio-cerebrovascular risk factors to AD, but also identify an indicated intervention. CAUSE+ABI are simple to perform, cost-effective, non-invasive, and reasonably accurate for the intended purpose. Additionally, detection of cardio-cerebrovasacular abnormalities long before expression of cognitive deterioration allows higher success rate with earlier treatment. Evidence-based medicine is recommended for optimizing clinical decision-making in evaluating AD risk factors and their treatment.", "title": "Alzheimer's disease is incurable but preventable." }, { "docid": "MED-994", "text": "Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.", "title": "Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment" }, { "docid": "MED-3452", "text": "Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.", "title": "Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation?" }, { "docid": "MED-1499", "text": "Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and nuts. The diverse array of bioactive nutrients present in these natural products plays a pivotal role in prevention and cure of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and other neuronal dysfunctions. Accumulated evidence suggests that naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function. Nuts such as walnut have also demonstrated neuroprotective effect against AD. The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signalling pathways associated with protein folding and neuroinflammation. The neuroprotective effects of various naturally occurring compounds in AD is evaluating in this review.", "title": "Neuroprotective effect of natural products against Alzheimer's disease." }, { "docid": "MED-2794", "text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.", "title": "Dietary turmeric potentially reduces the risk of cancer." }, { "docid": "MED-1498", "text": "Many studies have documented the role of risk and protective factors for late life dementing illnesses, particularly Alzheimer's disease. A \"Systematic Review\" from the US Agency for Healthcare Research and Quality and the National Institute on Aging concluded that because the overall quality of evidence was low, recommendations for public health could not be made. In order to gain evidence for the efficacy of lifestyle interventions, we propose a \"Modest Proposal\" to study 10,000 subjects over 40 years randomly assigned to groups of low or high saturated fat in the diet, head injury, and high or low levels of mental activity, physical activity, or inactivity as well as smoking or non-smoking. This proposed study cannot be accomplished. The \"Modest Proposal\" illustrates that the absence of definitive evidence should not restrict physicians from making reasonable recommendations based on the evidence that is available.", "title": "A modest proposal for a longitudinal study of dementia prevention (with apologies to Jonathan Swift, 1729)." }, { "docid": "MED-4553", "text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.", "title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?" }, { "docid": "MED-2212", "text": "With the republication of Grant (18), the first paper providing epidemiologic evidence linking diet to the development of Alzheimer's disease (AD), it is an appropriate time to review the findings and hypotheses therein in light of the subsequent literature. The main findings, that dietary fat and energy in old age are high risk factors, while fish and cereals are risk-reduction factors, have been supported in various recent epidemiologic studies. Diet contributes to the development of AD through modulating oxidative stress and inflammation, which is also linked to oxidative stress, but may also arise from series 2 prostaglandins. Thus, as one ages, dietary modifications and additional supplements designed to reduce free radical production and inflammation provide a significant measure of reduction in risk for the development of AD.", "title": "Dietary links to Alzheimer's disease: 1999 update." }, { "docid": "MED-1436", "text": "PURPOSE OF REVIEW: Sirtuins are a family of enzymes highly conserved in evolution and involved in mechanisms known to promote healthy ageing and longevity. This review aims to discuss recent advances in understanding the role of sirtuins, in particular mammalian SIRT1, in promoting longevity and its potential molecular basis for neuroprotection against cognitive ageing and Alzheimer's disease pathology. RECENT FINDINGS: Accumulative increase in oxidative stress during ageing has been shown to decrease SIRT1 activity in catabolic tissue, possibly by direct inactivation by reactive oxygen. SIRT1 overexpression prevents oxidative stress-induced apoptosis and increases resistance to oxidative stress through regulation of the FOXO family of forkhead transcription factors. In addition, resveratrol strongly stimulates SIRT1 deacetylase activity in a dose-dependent manner by increasing its binding affinity to both the acetylated substrate and NAD(+). Recently, SIRT1 has been shown to affect amyloid production through its influence over the ADAM10 gene. Upregulation of SIRT1 can also induce the Notch pathway and inhibit mTOR signalling. SUMMARY: Recent studies have revealed some of the mechanisms and pathways that are associated with the neuroprotective effects of SIRT1.", "title": "Sirtuins in cognitive ageing and Alzheimer's disease." }, { "docid": "MED-2216", "text": "BACKGROUND: Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD. OBJECTIVE: This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible. METHODS: This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data. RESULTS: For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan. CONCLUSION: Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.", "title": "Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries." }, { "docid": "MED-1512", "text": "BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: \"placebo ingestion\" (n = 11), \"curcumin ingestion\" (n = 11), \"exercise training with placebo ingestion\" (n = 11), or \"exercise training with curcumin ingestion\" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.", "title": "Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study." }, { "docid": "MED-1282", "text": "Excitement about neurogenetics in the last two decades has diverted attention from environmental causes of sporadic ALS. Fifty years ago endemic foci of ALS with a frequency one hundred times that in the rest of the world attracted attention since they offered the possibility of finding the cause for non-endemic ALS throughout the world. Research on Guam suggested that ALS, Parkinson's disease and dementia (the ALS/PDC complex) was due to a neurotoxic non-protein amino acid, beta-methylamino-L-alanine (BMAA), in the seeds of the cycad Cycas micronesica. Recent discoveries that found that BMAA is produced by symbiotic cyanobacteria within specialized roots of the cycads; that the concentration of protein-bound BMAA is up to a hundred-fold greater than free BMAA in the seeds and flour; that various animals forage on the seeds (flying foxes, pigs, deer), leading to biomagnification up the food chain in Guam; and that protein-bound BMAA occurs in the brains of Guamanians dying of ALS/PDC (average concentration 627 microg/g, 5 mM) but not in control brains have rekindled interest in BMAA as a possible trigger for Guamanian ALS/PDC. Perhaps most intriguing is the finding that BMAA is present in brain tissues of North American patients who had died of Alzheimer's disease (average concentration 95 microg/g, 0.8mM); this suggests a possible etiological role for BMAA in non-Guamanian neurodegenerative diseases. Cyanobacteria are ubiquitous throughout the world, so it is possible that all humans are exposed to low amounts of cyanobacterial BMAA, that protein-bound BMAA in human brains is a reservoir for chronic neurotoxicity, and that cyanobacterial BMAA is a major cause of progressive neurodegenerative diseases including ALS worldwide. Though Montine et al., using different HPLC method and assay techniques from those used by Cox and colleagues, were unable to reproduce the findings of Murch et al., Mash and colleagues using the original techniques of Murch et al. have recently confirmed the presence of protein-bound BMAA in the brains of North American patients dying with ALS and Alzheimer's disease (concentrations >100 microg/g) but not in the brains of non-neurological controls or Huntington's disease. We hypothesize that individuals who develop neurodegenerations may have a genetic susceptibility because of inability to prevent BMAA accumulation in brain proteins and that the particular pattern of neurodegeneration that develops depends on the polygenic background of the individual.", "title": "Beyond Guam: the cyanobacteria/BMAA hypothesis of the cause of ALS and other neurodegenerative diseases." }, { "docid": "MED-4590", "text": "Increased oxidative stress contributes to the decline in cognitive performance during normal aging and in neurodegenerative conditions such as Alzheimer's disease. Dietary supplementation with fruits and vegetables that are high in antioxidant potential have in some cases compensated for oxidative stress. Herein, we examined whether apple juice could alleviate the neurotoxic consequences of exposure of cultured neuronal cells to amyloid-beta (Abeta), since at least a portion of the neurotoxicity of Abeta is due to oxidative stress. Apple juice concentrate (AJC; 70 degree brix) was diluted into culture medium of SH-SY-5Y human neuroblastoma cells that had been differentiated for 7 days with 5 microM retinoic acid concurrent with the addition of 20 microM Abeta. AJC prevented the increased generation of reactive oxygen species (ROS) normally induced by Abeta treatment under these conditions. AJC also prevented Abeta-induced calcium influx and apoptosis, each of which results in part due to increased ROS. These findings suggest that the antioxidant potential of apple products can prevent Abeta-induced oxidative damage.", "title": "Apple juice prevents oxidative stress induced by amyloid-beta in culture." }, { "docid": "MED-3535", "text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.", "title": "Cherries and health: a review." }, { "docid": "MED-2211", "text": "BACKGROUND: China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. METHODS: In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. FINDINGS: Our search returned 12,642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340,247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254,367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0-44·4) at 65-69 years, and 42·1% (0·0-88·9) at age 95-99 years. In 2010 prevalence was 2·6% (0·0-28·2) at age 65-69 years and 60·5% (39·7-81·3) at age 95-99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22-5·14) in 1990, 5·62 million (4·42-6·82) in 2000, and 9·19 million (5·92-12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15-2·71) in 1990, 3·71 million (2·84-4·58) people in 2000, and 5·69 million (3·85-7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20,157 healthy controls, who were followed up for 3-7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74-2·45). INTERPRETATION: Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. FUNDING: Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia-China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis." }, { "docid": "MED-2218", "text": "OBJECTIVE: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. DESIGN AND SETTING: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. PARTICIPANTS: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. MAIN OUTCOME MEASURES: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. RESULTS: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. CONCLUSIONS: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.", "title": "Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study." }, { "docid": "MED-987", "text": "BACKGROUND: In cross-sectional studies, elevated plasma homocysteine levels have been associated with poor cognition and dementia. Studies of newly diagnosed dementia are required in order to establish whether the elevated homocysteine levels precede the onset of dementia or result from dementia-related nutritional and vitamin deficiencies. METHODS: A total of 1092 subjects without dementia (667 women and 425 men; mean age, 76 years) from the Framingham Study constituted our study sample. We examined the relation of the plasma total homocysteine level measured at base line and that measured eight years earlier to the risk of newly diagnosed dementia on follow-up. We used multivariable proportional-hazards regression to adjust for age, sex, apolipoprotein E genotype, vascular risk factors other than homocysteine, and plasma levels of folate and vitamins B12 and B6. RESULTS: Over a median follow-up period of eight years, dementia developed in 111 subjects, including 83 given a diagnosis of Alzheimer's disease. The multivariable-adjusted relative risk of dementia was 1.4 (95 percent confidence interval, 1.1 to 1.9) for each increase of 1 SD in the log-transformed homocysteine value either at base line or eight years earlier. The relative risk of Alzheimer's disease was 1.8 (95 percent confidence interval, 1.3 to 2.5) per increase of 1 SD at base line and 1.6 (95 percent confidence interval, 1.2 to 2.1) per increase of 1 SD eight years before base line. With a plasma homocysteine level greater than 14 micromol per liter, the risk of Alzheimer's disease nearly doubled. CONCLUSIONS: An increased plasma homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer's disease.", "title": "Plasma homocysteine as a risk factor for dementia and Alzheimer's disease." }, { "docid": "MED-3936", "text": "Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.", "title": "Elevated Serum Pesticide Levels and Risk of Parkinson Disease" }, { "docid": "MED-4669", "text": "RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer's disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer's disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).", "title": "A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease." }, { "docid": "MED-1848", "text": "BACKGROUND: In a cross-sectional case-control study conducted in northern Italy, 64 former aluminium dust-exposed workers were compared with 32 unexposed controls from other companies matched for age, professional training, economic status, educational and clinical features. The findings lead the authors to suggest a possible role of the inhalation of aluminium dust in pre-clinical mild cognitive disorder which might prelude Alzheimer's disease (AD) or AD-like neurological deterioration. METHODS: The investigation involved a standardised occupational and medical history with particular attention to exposure and symptoms, assessments of neurotoxic metals in serum: aluminium (Al-s), copper (Cu-s) and zinc (Zn-s), and in blood: manganese (Mn-b), lead (Pb-b) and iron (Fe-b). Cognitive functions were assessed by the Mini Mental State Examination (MMSE), the Clock Drawing Test (CDT) and auditory evoked Event-Related Potential (ERP-P300). To detect early signs of mild cognitive impairment (MCI), the time required to solve the MMSE (MMSE-time) and CDT (CDT-time) was also measured. RESULTS: Significantly higher internal doses of Al-s and Fe-b were found in the ex-employees compared to the control group. The neuropsychological tests showed a significant difference in the latency of P300, MMSE score, MMSE-time, CDT score and CDT-time between the exposed and the control population. P300 latency was found to correlate positively with Al-s and MMSE-time. Al-s has significant effects on all tests: a negative relationship was observed between internal Al concentrations, MMSE score and CDT score; a positive relationship was found between internal Al concentrations, MMSE-time and CDT-time. All the potential confounders such as age, height, weight, blood pressure, schooling years, alcohol, coffee consumption and smoking habit were taken into account. CONCLUSIONS: These findings suggest a role of aluminium in early neurotoxic effects that can be detected at a pre-clinical stage by P300, MMSE, MMSE-time, CDT-time and CDT score, considering a 10 micrograms/l cut-off level of serum aluminium, in aluminium foundry workers with concomitant high blood levels of iron. The authors raise the question whether pre-clinical detection of aluminium neurotoxicity and consequent early treatment might help to prevent or retard the onset of AD or AD-like pathologies.", "title": "Neurotoxic effects of aluminium among foundry workers and Alzheimer's disease." }, { "docid": "MED-4580", "text": "Preclinical studies demonstrate that apple juice exerts multiple beneficial effects including reduction of central nervous system oxidative damage, suppression of Alzheimer's disease (AD) hallmarks, improved cognitive performance, and organized synaptic signaling. Herein, we initiated an open-label clinical trial in which 21 institutionalized individuals with moderate-to-severe AD consumed 2 4-oz glasses of apple juice daily for 1 month. Participants demonstrated no change in the Dementia Rating Scale, and institutional caregivers reported no change in Alzheimer's Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) in this brief study. However, caregivers reported an approximate 27% (P < .01) improvement in behavioral and psychotic symptoms associated with dementia as quantified by the Neuropsychiatric Inventory, with the largest changes in anxiety, agitation, and delusion. This pilot study suggests that apple juice may be a useful supplement, perhaps to augment pharmacological approaches, for attenuating the decline in mood that accompanies progression of AD, which may also reduce caregiver burden.", "title": "Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer's disease in an open-label pilot study." }, { "docid": "MED-3577", "text": "PROBLEM/CONDITION: During the twenty first century, growth in the number of older adults (persons aged > or =65 years) in the United States will produce an unprecedented increase in the number of persons at risk for costly age-associated chronic diseases and other health conditions and injuries. REPORTING PERIOD: 1995-1996. DESCRIPTION OF SYSTEMS: This report uses data from CDC's National Center for Health Statistics (NCHS) to report on leading causes of death in 1996 (from the National Vital Statistics System), major causes of hospitalization (1996 National Hospital Discharge Survey [NHDSI), and major chronic conditions (1995 National Health Interview Survey [NHIS]). The National Vital Statistics System compiles information regarding all death certificates filed in the United States. NHDS is an annual probability sample of discharges from nonfederal, short-stay hospitals. NHIS is an ongoing annual cross-sectional household survey of the U.S. civilian, noninstitutionalized population. In addition, health-care expenditures for older adults are examined by using information obtained from published reports from the U.S. Health Care Financing Administration (HCFA) and health-services literature. RESULTS: The leading causes of death among adults aged > or =65 years were heart disease (1,808 deaths/100,000 population), malignant neoplasms (1,131/100,000), and cerebrovascular disease (415/100,000). Several leading causes of mortality among older adults differed by race, with deaths caused by Alzheimer's disease more frequent among whites and deaths caused by diabetes, kidney diseases, septicemia, and hypertension more frequent among blacks. Rates of hospitalization and length of hospital stays increased with age. Hospitalizations for heart disease represented the highest proportion of all discharges among older adults (23%). Discharge rates for malignant neoplasms, stroke, and pneumonia were similar for adults aged > or =65 years and, as with heart disease, were higher for men than for women. However, the rate of hospitalization for fractures among women exceeded the rate among men. Arthritis was the most prevalent chronic condition among adults aged > or =65 years (48.9/100 adults), followed by hypertension (40.3/100) and heart disease (28.6/100). In 1995, adults aged > or =65 years comprised 13% of the population but accounted for 35% of total personal health care dollars spent ($310 billion), and real per capita personal health-care expenditure for this age group increased at an average annual rate of 5.8% during 1985-1995. Projections for future medical expenditures for older adults vary; however, all project substantial increases after the year 2000. Hip fracture, dementia, and urinary incontinence are discussed as examples of prevalent and costly health conditions among older adults that differ in potential for prevention. These conditions were selected because they result in substantial medical and social costs and they differ in potential for prevention. INTERPRETATION: The higher prevalence of serious and costly health conditions among adults aged > or =65 years highlights the importance of implementing preventive health measures in this population. PUBLIC HEALTH ACTIONS: Data regarding causes of morbidity, mortality, and health-care expenditures among older adults provide information for measuring the effectiveness of public health efforts to reduce modifiable risk factors for morbidity and mortality in this population.", "title": "Surveillance for morbidity and mortality among older adults--United States, 1995-1996." }, { "docid": "MED-1939", "text": "Introduction Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. Methods We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Results Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL). Conclusions Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound. Trial registration ClinicalTrials.gov Identifier: NCT00099710.", "title": "Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study" }, { "docid": "MED-1506", "text": "Intake of saturated fats and simple carbohydrates, two of the primary components of a modern Western diet, is linked with the development of obesity and Alzheimer's Disease. The present paper summarizes research showing that Western diet intake is associated with cognitive impairment, with a specific emphasis on learning and memory functions that are dependent on the integrity of the hippocampus. The paper then considers evidence that saturated fat and simple carbohydrate intake is correlated with neurobiological changes in the hippocampus that may be related to the ability of these dietary components to impair cognitive function. Finally, a model is described proposing that Western diet consumption contributes to the development of excessive food intake and obesity, in part, by interfering with a type of hippocampal-dependent memory inhibition that is critical in the ability of animals to refrain from responding to environmental cues associated with food, and ultimately from consuming energy intake in excess of that driven solely by caloric need.", "title": "Western Diet Consumption and Cognitive Impairment: Links to Hippocampal Dysfunction and Obesity" }, { "docid": "MED-726", "text": "OBJECTIVE: The relationship between lipid profiles and Alzheimer disease (AD) pathology at the population level is unclear. We searched for evidence of AD-related pathologic risk of abnormal lipid metabolism. METHODS: This study included brain specimens from a series of 147 autopsies performed between 1998 and 2003 of residents in Hisayama town, Japan (76 men and 71 women), who underwent clinical examinations in 1988. Lipid profiles, such as total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDLC), were measured in 1988. Low-density lipoprotein cholesterol (LDLC) was calculated using the Friedewald formula. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines (CERAD) and neurofibrillary tangles (NFTs) were assessed according to Braak stage. Associations between each lipid profile and AD pathology were examined by analysis of covariance and logistic regression analyses. RESULTS: Adjusted means of TC, LDLC, TC/HDLC, LDLC/HDLC, and non-HDLC (defined as TC-HDLC) were significantly higher in subjects with NPs, even in sparse to moderate stages (CERAD = 1 or 2), compared to subjects without NPs in multivariate models including APOE ε4 carrier and other confounding factors. The subjects in the highest quartiles of these lipid profiles had significantly higher risks of NPs compared to subjects in the lower respective quartiles, which may suggest a threshold effect. Conversely, there was no relationship between any lipid profile and NFTs. CONCLUSION: The results of this study suggest that dyslipidemia increases the risk of plaque-type pathology.", "title": "Association of Alzheimer disease pathology with abnormal lipid metabolism: the Hisayama Study." }, { "docid": "MED-1500", "text": "BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.", "title": "Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies." } ]
5a8f868f55429918e830d24f	Evey Hammond is a fictional character and the protagonist of the comic book series, "V for Vendetta", created by which two people, she becomes involved in V 's life, when he rescues her from a gang of London's secret police, V is the title character of the comic book series "V for Vendetta"?	[ { "docid": "4566771", "text": "Evey Hammond is a fictional character and the protagonist of the comic book series, \"V for Vendetta\", created by Alan Moore and David Lloyd. She becomes involved in V's life when he rescues her from a gang of London's secret police.", "title": "" }, { "docid": "4553266", "text": "V is the title character of the comic book series \"V for Vendetta\", created by Alan Moore and David Lloyd. He is a mysterious anarchist, vigilante, and freedom fighter who is easily recognizable by his Guy Fawkes mask, long hair and dark clothing. He strives to topple a totalitarian government of a dystopian United Kingdom through acts of terrorism. According to Moore, he was designed to be morally ambiguous, so that readers could decide for themselves whether he was a hero fighting for a cause or simply insane.", "title": "" } ]	[ { "docid": "73257", "text": "V for Vendetta is a British graphic novel written by Alan Moore and illustrated by David Lloyd (with additional art by Tony Weare), published by DC Comics. Later versions were published by Vertigo, an imprint of DC Comics. The story depicts a dystopian and post-apocalyptic near-future history version of the United Kingdom in the 1990s, preceded by a nuclear war in the 1980s which had devastated most of the rest of the world. The fascist Norsefire party has exterminated its opponents in concentration camps and rules the country as a police state. The comics follow its title character and protagonist, V, an anarchist revolutionary dressed in a Guy Fawkes mask, as he begins an elaborate and theatrical revolutionist campaign to kill his former captors, bring down the fascist state and convince the people to abandon democracy in favour of anarchy, while inspiring a young woman, Evey Hammond, to be his protégé.", "title": "" }, { "docid": "5860947", "text": "Adam James Susan is a fictional character and the main antagonist of the comic book series (later graphic novel) \"V for Vendetta\", created by writer Alan Moore and illustrator David Lloyd. He is renamed Adam Sutler (the surname being a portmanteau of \"Susan\" and \"Hitler\") in the film adaptation, in which he is portrayed by John Hurt.", "title": "" }, { "docid": "1891886", "text": "V for Vendetta is a 2005 dystopian political thriller film directed by James McTeigue and written by The Wachowskis, based on the 1988 DC/Vertigo Comics limited series of the same name by Alan Moore and David Lloyd. The film is set in an alternative future where a neo-fascist regime has subjugated the United Kingdom. Hugo Weaving portrays V, an anarchist freedom fighter who attempts to ignite a revolution through elaborate terrorist acts and Natalie Portman plays Evey, a young, working-class woman caught up in V's mission, while Stephen Rea portrays the detective leading a desperate quest to stop V.", "title": "" }, { "docid": "4973646", "text": "Norsefire is the fictional fascist political party ruling the United Kingdom in Alan Moore and David Lloyd's \"V for Vendetta\" comic book series.", "title": "" }, { "docid": "1850041", "text": "Citizen V is the codename of several fictional superheroes appearing in American comic books published by Marvel Comics. The original incarnation was an obscure hero from the Golden Age of Comic Books, but the character's identity was revived in the modern day in the pages of \"Thunderbolts\". The various incarnations of the character have usually been affiliated with the V-Battalion organization. The \"V\" in the character's and group's name is the letter \"V\" - as opposed to the Roman numeral 5 - and is derived from the World War II-era slogan \"V for Victory\".", "title": "" }, { "docid": "8264027", "text": "The V-Battalion is the name of two incarnations of a fictional secret organization composed of Golden Age superheroes and their descendents appearing in American comic books published by Marvel Comics. The organization featured prominently in the original Thunderbolts series and \"The New Invaders\".", "title": "" }, { "docid": "17704519", "text": "Maria V. Snyder is an American fantasy author best known for her \"Study Series\". Her first novel, \"Poison Study\", was published on October 2005, and won the 2006 Compton Crook Award for Best First Novel. the next two books in the series are \"Magic Study\" and \"Fire Study\". Snyder then released another trilogy of books, the \"Glass\" series, following the character Opal Cowan from the \"Study Series\". The books in the series are \"Storm Glass\", \"Sea Glass\" and \"Spy Glass\" respectively. On 24 February, Snyder went back to the main characters of the \"Study Series\" and released the first book of he next trilogy, the \"Soulfinder Series\", the first book of which is \"Shadow Study\". Aside from writing, her interests include \"traveling, photography, making jewelry, and volleyball.\"", "title": "" }, { "docid": "9105", "text": "DC Comics, Inc. is an American comic book publisher. It is the publishing unit of DC Entertainment, a subsidiary of Warner Bros. Entertainment, Inc., a division of Time Warner. DC Comics is one of the largest and oldest American comic book companies, and produces material featuring numerous well-known heroic characters including Superman, Batman, Wonder Woman, Green Lantern, the Flash, Aquaman, Hawkman, and Green Arrow. Most of their material takes place in the fictional DC Universe, which also features teams such as the Justice League, the Justice Society of America, the Suicide Squad, and the Teen Titans, and well-known villains such as the Joker, Lex Luthor, The Cheetah, Harley Quinn, Darkseid, Catwoman, Ra's al Ghul, Deathstroke, Reverse-Flash, Sinestro, Black Adam, and Brainiac. The company has also published non-DC Universe-related material, including \"Watchmen\", \"V for Vendetta\", and many titles under their alternative imprint Vertigo.", "title": "" }, { "docid": "4302881", "text": "V for Vendetta: Music From The Motion Picture is the soundtrack from the 2006 film \"V for Vendetta\", released by Astralwerks Records on March 21, 2006. Most of the music was written by Dario Marianelli. Other artists include Julie London, Cat Power and Antony and the Johnsons.", "title": "" }, { "docid": "25881097", "text": "Darwin Jones is a fictional scientist, a comic book character published by DC Comics. He first appeared in \"Strange Adventures\" #1 (August 1950), and was created by David V Reed and Paul Norris.", "title": "" }, { "docid": "12717210", "text": "The Crow is a fictional character and the protagonist of \"The Crow\" comic book series, originally created by American artist James O'Barr in 1989. The titular character is an undead vigilante brought back to life by a supernatural crow to avenge his murder and that of his fiancée. The character has subsequently appeared in several feature films, a television series, and spin-off novels and comics. In the various incarnations, films, and spin-offs, many people have taken on the Crow persona in order to avenge their own wrongful deaths. In 2011, IGN ranked the Crow 37th in the Top 100 Comic Book Heroes.", "title": "" }, { "docid": "54195638", "text": "Killeroo is a fictional character appearing in Australian comic book \"Captain Koala\". All of the characters in the series were created by James Clifton. Killeroo started as a Level 2 agent in Captain Koala #1, by issue #10 gets promoted to Level 1. He is now appearing in solo titles such as Killeroo: Gang Wars by artist Tim Stiles Professional comic book artist Darren Close has created many comics featuring Killeroo. Killeroo also appeared in Gold Age comics", "title": "" }, { "docid": "966193", "text": "Jade is a fictional character from the \"Mortal Kombat\" fighting game series by Midway Games. Debuting in 1993's \"Mortal Kombat II\" as an unplayable secret character who was a green palette swap of Kitana, Jade made her first playable appearance in \"Ultimate Mortal Kombat 3\". She has since become a regular supporting character in the franchise, appearing on series merchandise in addition to alternate \"Mortal Kombat\" media, such as comic books and the feature film \".\"", "title": "" }, { "docid": "30487893", "text": "Solstice is a fictional comic book super heroine published by DC Comics. The character is set to appear as a new member in DC's long-running \"Teen Titans\" comic book series, and was created by JT Krul and Nicola Scott. Krul has described the character as being \"a positive spirit - influenced by the various cultures she’s encountered during her travels throughout the world. She embraces life and all the adventure and experiences it offers.\"", "title": "" }, { "docid": "15154793", "text": "Maggy (original \"Magali\"), is a character of the popular Brazilian comic book series \"Monica's Gang\". She was created by Mauricio de Sousa, who based the character on one of his daughters, Magali Spada e Souza. Monica, Mary Angela (Jimmy's sister) and Marina were also based on Mauricio's daughters. Maggy has her own comic book, in which there are also stories of her cat, Vanilla.", "title": "" }, { "docid": "3352265", "text": "Vendetta for the Saint is a 1964 mystery novel featuring the character of Simon Templar, alias \"The Saint\". The novel is credited to Leslie Charteris, who created the Saint in 1928, but the book was actually authored by Harry Harrison, a noted science fiction author who also wrote the syndicated \"Saint\" comic strip. Although Harrison wrote the majority of the book as a ghost writer, he indicates in an interview that Charteris did contribute to the final book (albeit in a very minor way)..", "title": "" }, { "docid": "25677986", "text": "Hit-Girl (Mindy McCready (comic) or Macready (film)) is a fictional character appearing in the \"Kick-Ass\" series, published by Marvel Comics under the company's imprint Icon Comics. The character was created by artist John Romita, Jr. and writer Mark Millar. She is a young but effective vigilante, trained by her father Damon McCready (a.k.a. Big Daddy) from an early age to be a costumed superhero and assassin. In \"Kick-Ass\", she is introduced as a supporting character. She featured in her own self-titled comic book series, \"Hit-Girl\", which was first published on 27 June 2012. She is portrayed by Chloë Grace Moretz in the feature film adaptations \"Kick-Ass\" and \"Kick Ass 2\".", "title": "" }, { "docid": "29871663", "text": "Kick-Ass (real name David \"Dave\" Lizewski) is a title character and the protagonist of the \"Kick-Ass\" series, published by Marvel Comics under the company’s imprint Icon Comics. The character was created by artist John Romita, Jr. and writer Mark Millar. Prior to the series, Dave Lizewski is a high school student and comic book fan whose dreams inspire him to become a real life superhero, going by the name \"Kick-Ass\", with no superpowers or training of any kind. He is portrayed by Aaron Taylor-Johnson in the feature film adaptations \"Kick-Ass\" and \"Kick-Ass 2\".", "title": "" }, { "docid": "3683472", "text": "Mister E is a fictional character, appearing in magazines published by American company DC Comics. Created by Bob Rozakis and Jack C. Harris, the character first appeared in \"Secrets of Haunted House\" and was a recurring character for ten issues. He was then radically redesigned by Neil Gaiman for use in \"The Books of Magic\", after which he appeared in his own mini-series and was a recurring character in Vertigo Comics titles owned by DC.", "title": "" }, { "docid": "43098096", "text": "Livewire is a fictional character that appears in comic books published by Valiant Comics. Created by Bob Layton and Joe St. Pierre. Bob came up with the name Livewire and assigned her the electromagnetic harbinger abilities. Joe did everything else, designed the character, named her Amanda McKee, filled in her personal history where he could. Livewire first appeared in \"Harbinger\" #14 (1993). She later played a major role in the \"Secret Weapons\" (1993) limited series. Valiant Entertainment is the current owner of Livewire and the rest of the original Valiant Comics characters.", "title": "" }, { "docid": "54477477", "text": "Secret Warriors is a Marvel Comics title. The title has been used for two comic book series focusing on two separate teams of young superpowered characters.", "title": "" }, { "docid": "2071717", "text": "Lucas \"Snapper\" Carr is a fictional character appearing in American comic books published by DC Comics. The character, whose fictional nickname is almost always used by other characters in favor of his given name, was created by Gardner Fox (writer) and Mike Sekowsky (penciller), and made his first appearance in \"The Brave and the Bold\" in February 1960. From 1960 to 1969, Snapper Carr appeared as a supporting character to the Justice League of America, a superhero team. The character occasionally appeared in comics featuring the Justice League from 1969 to 1989, when the \"Invasion!\" limited-series comic book gave him superpowers. He was associated with a new superhero team, The Blasters, in various comics until 1993, when he lost his powers and became a main character in the \"Hourman\" comic book. After the cancellation of \"Hourman\" in April 2001, he became a main character in the \"Young Justice\" comic book beginning in December 2001. \"Young Justice\" was cancelled in May 2003, and he became associated with the governmental organization Checkmate, a role revealed when the character played a small but important role in the 2007-2008 limited series comic book \"52 Aftermath: The Four Horsemen\". The character made major appearances in \"Final Crisis: Resist\" in December 2008 and \"Justice League of America 80-Page Giant\" in November 2009.", "title": "" }, { "docid": "42634977", "text": "Elaine Banner or Elaine Walters is a fictional and supporting character appearing in American comic books published by Marvel Comics. The character appeared later in multiple spin-offs and dramatizations of the \"Hulk\" and She-Hulk comic book titles. She was created by writer David Kraft and artist Mike Vosburg. She first appeared in \"The Savage She-Hulk\" Vol 1 #15 of April, in 1981. She is the sister of Susan and Brian Banner, the wife of Morris Walters, and the Aunt of Bruce Banner who would grow up to be the Gamma-Powered superhero known as the Hulk; while her daughter and Bruce's cousin would become the super-heroine known as The She-Hulk, when Bruce saved her life with a blood transfusion.", "title": "" }, { "docid": "33969123", "text": "Razor is a fictional character from the London Night Studios series \"Razor\". She was introduced in \"Razor\" #1 in October 1992, in her own self-titled comic book by writer/creator Everette Hartsoe.", "title": "" }, { "docid": "49224270", "text": "\"Lucifer\" is an American fantasy police procedural dramedy television series developed by Tom Kapinos that premiered on Fox on January 25, 2016. It features a character created by Neil Gaiman, Sam Kieth, and Mike Dringenberg taken from the comic book series \"The Sandman\", which later became the protagonist of the spin-off comic book series \"Lucifer\" written by Mike Carey, both published by DC Comics' Vertigo imprint.", "title": "" }, { "docid": "30871487", "text": "Dead Girl (Moonbeam) is a fictional character, a mutant superheroine appearing in American comic books published by Marvel Comics. The character appeared primarily in the \"X-Statix\" series. She is a mixture of ghost and zombie. Her civilian name has never been fully revealed, but she admitted after some cajoling that her first name is/was \"Moonbeam.\" Dead Girl's mutant gene allows her to return to semi-life after dying; she is also able to become intangible and communicate with other dead people.", "title": "" }, { "docid": "47600187", "text": "Nero is a Flemish comic book character and the main protagonist in Marc Sleen's long running comic book strip series \"The Adventures of Nero\" (1947–2002). He is one of the most recognizable comic book characters in Belgium and comparable to Lambik from the \"Suske en Wiske\" series by Willy Vandersteen.", "title": "" }, { "docid": "853327", "text": "John V. Romita Sr., often credited as simply John Romita ( ; born January 24, 1930), is an American comic-book artist best known for his work on Marvel Comics' \"The Amazing Spider-Man\" and for co-creating the character The Punisher. He was inducted into the Will Eisner Comic Book Hall of Fame in 2002.", "title": "" }, { "docid": "3997446", "text": "Milla Donovan is a fictional character appearing in American comic books published by Marvel Comics. She is usually depicted as a supporting character in the comic-book series \"Daredevil\". She was created by Brian Michael Bendis and Alex Maleev and first appeared in \"Daredevil\" vol. 2 #41 (2003). Her appearance was modeled after that of Maleev's wife.", "title": "" }, { "docid": "41360454", "text": "Tara Chambler is a fictional character from the horror drama television series \"The Walking Dead\", which airs on AMC in the United States and is based on the comic book series of the same name\".\" The character is based on Tara Chalmers from \"\", a novel based on the comic book series and the past of the Governor. She is portrayed by Alanna Masterson. She is the first character identified as LGBT to be introduced in the series.", "title": "" } ]
5a836efa554299123d8c211d	Which is native to farther east, Punch or Chimayó Cocktail?	[ { "docid": "441561", "text": "Punch is a wide assortment of drinks, both non-alcoholic and alcoholic, generally containing fruit or fruit juice. The drink was introduced from India to the United Kingdom in the early seventeenth century, and from there its use spread to other countries. Punch is typically served at parties in large, wide bowls, known as \"punch bowls\".", "title": "" }, { "docid": "15978737", "text": "The Chimayó cocktail was created by Arturo Jaramillo, owner of the Rancho de Chimayó restaurant in Chimayó, New Mexico in 1965, the Chimayó Cocktail is a tequila and apple cider based drink. Legend has it that Jaramillo was looking for use for the apples that are plentiful in the Chimayó valley when he stumbled onto what would soon become the signature drink of his restaurant.", "title": "" } ]	[ { "docid": "46678089", "text": "Donkey Punch is a punch or cocktail made of 1 part rum, 3 parts orange juice, 2 parts ginger ale, 1 part pineapple juice and Grenadine syrup. The ingredients are poured into shaker filled with ice and shaken well befoure pouring it into a large glass filled with ice cubes. The ingredients can also be mixed together in a punch bowl and served with ice and orange slices floating on top.", "title": "" }, { "docid": "31069876", "text": "Curacao Punch is a cocktail that comes from Harry Johnson's New and Improved Bartender's Manual (1882). Dale DeGroff, a notable bartender and author of The Craft of the Cocktail (Clarkson Potter, 2002), holds this to be his favorite forgotten potation.", "title": "" }, { "docid": "18317856", "text": "Planter's Punch is an IBA Official Cocktail made of dark rum, several juices, grenadine syrup, sugar syrup, and Angostura bitters.", "title": "" }, { "docid": "13119009", "text": "Pacific Union Club Punch is a drink in William \"Cocktail\" Boothby's 1908 work \"The World's Drinks And How To Mix Them\" with the recipe:", "title": "" }, { "docid": "53777101", "text": "The Russian Spring Punch is a highball cocktail of vodka and liqueur, per IBA specified ingredients, the International Bartenders Association lists the beverage in its New Era Drinks category", "title": "" }, { "docid": "150791", "text": "Chimayó is a census-designated place (CDP) in Rio Arriba and Santa Fe counties in the U.S. state of New Mexico; the name derives from a Tewa name for a local landmark, the hill of Tsi Mayoh. The town is unincorporated and includes many neighborhoods, called plazas or placitas, each with its own name, including El Potrero de Chimayó (the plaza near Chimayó's communal pasture) and the Plaza del Cerro (plaza by the hill). The cluster of plazas called Chimayó lies near Santa Cruz about 25 miles north of Santa Fe. The population was 3,177 at the 2010 census.", "title": "" }, { "docid": "2471254", "text": "Farther Common is a geographical region of East Hampshire in the Parish of Liss, Hampshire, England. It is characterised by greensand topography, woodland and heath, which was a common on the Money-Coutts estate centred at Stodham House, Liss. The name of this common land is in fact \"Farther Commons\" which can be verified by reference to the ordnance survey map of the area.", "title": "" }, { "docid": "45545482", "text": "Picon Punch, or simply Picon, is a highball cocktail made with an Amaro liqueur, soda water, grenadine, a splash of lemon, and a bit of brandy floating on top. The drink is identified as Basque, but was created by Basque immigrants in the U.S. and taken back to the Basque region in the Pyrenees. It is popular in Basque Restaurants and Bars in Boise and southern Idaho, in Bakersfield, California, and Northern Nevada.", "title": "" }, { "docid": "21926080", "text": "The List of towns in Farther Pomerania includes towns that lost their town status over time as well as towns which lie west of the Oder river, but east of the Oder-Neisse line (\"Stettiner Zipfel\" area), and thus historically are associated rather with Vorpommern. The list also includes towns merged into the Province of Pomerania as late as 1938 and thus might not be regarded historically belonging to Farther Pomerania either.", "title": "" }, { "docid": "4122876", "text": "El Santuario de Chimayó is a Roman Catholic church in Chimayó, New Mexico, United States. (\"Santuario\" is Spanish for \"sanctuary\".) This shrine, a National Historic Landmark, is famous for the story of its founding and as a contemporary pilgrimage site. It receives almost 300,000 visitors per year and has been called \"no doubt the most important Catholic pilgrimage center in the United States.\"", "title": "" }, { "docid": "929458", "text": "The Suffolk Punch, also historically known as the Suffolk Horse or Suffolk Sorrel, is an English breed of draught horse. The breed takes the first part of its name from the county of Suffolk in East Anglia, and the name \"Punch\" from its solid appearance and strength. It is a heavy draught horse which is always chestnut in colour, traditionally spelled \"chesnut \" by the breed registries. Suffolk Punches are known as good doers, and tend to have energetic gaits.", "title": "" }, { "docid": "46781350", "text": "Arnoglossum reniforme (great Indian plantain) is a North American species of plants in the sunflower family. It is native to the central and east-central United States primarily in the Appalachian Mountains, the Ohio/Tennessee Valley, and the Mississippi Valley. There are additional populations in the east (New Jersey, Maryland, Pennsylvania, South Carolina) and farther west in Oklahoma.", "title": "" }, { "docid": "17600154", "text": "Broughton Strait is a strait off the north coast of Vancouver Island, British Columbia, Canada, separating that island from Malcolm and Cormorant Islands, on the farther side of which is the larger Queen Charlotte Strait, which also lies beyond the western end of Brouhgton Strait, and the mouth of Knight Inlet. Farther east from Broughton Strait is the beginning of Johnstone Strait, which leads via Discovery Passage to the Strait of Georgia.", "title": "" }, { "docid": "2315540", "text": "Farther Pomerania, Further Pomerania, Transpomerania or Eastern Pomerania (German: \"Hinterpommern, Ostpommern\" ), is the part of Pomerania which comprised the eastern part of the Duchy and later Province of Pomerania. It stretched roughly from the Oder River in the West to Pomerelia in the East. Since 1945 Farther Pomerania has been part of Poland; the bulk of former Farther Pomerania is within the West Pomeranian Voivodeship, while its easternmost parts are within the Pomeranian Voivodeship. The Polish term \"Pomorze Zachodnie\" (\"Western Pomerania\"), in modern Polish usage, is a synonym to the West Pomeranian Voivodship; in Polish historical usage it applied to all areas west of Pomerelia (i.e. whole narrow Pomerania).", "title": "" }, { "docid": "908981", "text": "A cocktail party is a party at which cocktails are served. It is sometimes called a cocktail reception. A cocktail party organized for purposes of social or business networking is called a mixer.", "title": "" }, { "docid": "17790689", "text": "Ribes missouriense, the Missouri gooseberry, Missouri currant or wild gooseberry, is a prickly, many-stemmed shrub native to the north-central United States (Great Lakes, upper Mississippi and lower Missouri Valleys). Scattered populations have been found farther east, most of them very likely escapes from cultivation.", "title": "" }, { "docid": "29386041", "text": "Tradescantia bracteata, the longbract spiderwort, or prairie spiderwort, is a species of \"Tradescantia\". It is native to the northern and central Great Plains and Mississippi Valley regions of the United States, from Arkansas and Oklahoma north to Minnesota and Montana, with a few isolated populations farther east. It is grown for its purple flowers. It blooms from May to July in the US.", "title": "" }, { "docid": "11836276", "text": "Squid cocktail is a seafood dish, which is usually served as an hors d'œuvre. It is similar to a prawn cocktail, but uses squid as the main ingredient.", "title": "" }, { "docid": "17699823", "text": "A leather punch is a hole punch specifically for making holes in leather. The working tip of the punch is a hollow steel cylinder with a sharp circular knife-like edge. The leather piece is placed on a hard surface, which may be a part of the tool set, and the punch is forced through it, cutting out a small circular piece which is discarded. The punch may be a simple metal tool struck with a hammer; or several such punches may be mounted on a rotary turret on a pliers-like tool with an anvil, with the desired size selected by rotating the turret. Hole diameters typically range from about 1mm to 6mm.", "title": "" }, { "docid": "4996440", "text": "A sucker punch (American English), also known as a coward punch, or cold-cock (American English), is a punch made without warning, allowing no time for preparation or defense on the part of the recipient. The term is generally used in situations where the way in which the punch has been delivered is considered unfair or unethical. In practice, this often includes punches delivered from behind. While the one hit punch and king hit (Australian English) is a different style of one-on-one fighting - pitting one individual against another . It can be considered as a sucker punch when the recipient isn't expecting it, or if they are unevenly matched by weight - which some people use to help strengthen the amount of force used .", "title": "" }, { "docid": "452268", "text": "Punch buggy (also called punch bug, punch car, punch dub, piggy punch, slug bug, or beetle bug) is a car game generally played by children in which participants punch each other on the arm upon first sight of a Volkswagen Beetle while calling out \"Punch buggy!\" or \"Slug bug!\" in reference to the Beetle's nickname, the Bug. The color of the Beetle is also sometimes stated.", "title": "" }, { "docid": "16662448", "text": "The Bay Breeze is a cocktail which has a Cape Codder as its base. This drink is also sometimes called a Downeaster, Hawaiian Sea Breeze or a Paul Joseph. This cocktail is similar to the Sea Breeze, which is an IBA Official Cocktail with grapefruit juice instead of pineapple juice.", "title": "" }, { "docid": "9361238", "text": "A wine cocktail is a mixed drink, similar to a true cocktail. It is made predominantly with wine (including Champagne and Prosecco), into which distilled alcohol or other drink mixer is combined.", "title": "" }, { "docid": "18697322", "text": "An Old Etonian is a gin cocktail which enjoyed great popularity in London, circa 1925. The cocktail takes its name from Eton College and from the college's alumni, who are often referred to as Old Etonians. The Garden Hotel in London is an example of an establishment that had mastered the Old Etonian cocktail during that era.", "title": "" }, { "docid": "46842817", "text": "Bradburia pilosa (soft goldenaster) is a North American species of flowering plants in the daisy family, native to the south-central United States, primarily the southeastern Great Plains and lower Mississippi Valley, in the states of Texas, Oklahoma, Kansas, Missouri, Arkansas, Louisiana, Tennessee, Mississippi, and Alabama. Additional populations are reported farther east (from Florida to Virginia) but these appear to be introductions.", "title": "" }, { "docid": "19984891", "text": "A punch bowl is a vessel in which punch is served.", "title": "" }, { "docid": "19184272", "text": "Punch-Out!! (パンチアウト!! , Panchi-Auto!! ) is a series of boxing video games created by Nintendo's general manager Genyo Takeda, and his partner Makoto Wada. It started in the Nes simply as \"Punch-Out!!\", which was followed by a sequel \"Super Punch-Out!!\". It has since spanned home consoles, including the Famicom and NES \"\"Punch-Out!! / Mike Tyson's Punch-Out!!\", an SNES and Super Famicom sequel \"Super Punch-Out!!\", and a Wii sequel \"Punch-Out!!\". In November 2009, Platinum Club Nintendo members received a code to download \"Doc Louis's Punch-Out!!\", which features a fight between series protagonist Little Mac and his mentor Doc Louis. The series also had a spin-off called \"Arm Wrestling\". Arm Wrestling was released only in North American arcades, and was Nintendo's last arcade game they independently developed and released.", "title": "" }, { "docid": "7051816", "text": "The Bronx Cocktail is essentially a Perfect Martini with orange juice added. It was ranked number three in \"The World's 10 Most Famous Cocktails in 1934\", making it a very popular rival to the Martini (#1) and the Manhattan (#2). Today, it remains a popular choice in some markets, and was formerly designated as an Official Cocktail by the International Bartender Association. Like the Manhattan, the Bronx is one of five cocktails named for one of New York City's five boroughs, but is perhaps most closely related to the Queens, which substitutes pineapple for the Bronx's orange.", "title": "" }, { "docid": "14041023", "text": "A punch bowl is a bowl, often large and wide, in which the drink punch is served.", "title": "" }, { "docid": "26832757", "text": "Melbourne Punch (from 1900, simply titled \"Punch\") (2 August 1855 – December 1925) was an Australian illustrated magazine founded by Edgar Ray and Frederick Sinnett, modelled closely on \"Punch\" of London which was founded fifteen years earlier. A similar magazine, \"Adelaide Punch\", was published in South Australia from 1878 to 1884.", "title": "" } ]
224	Cancer-associated fibroblasts (CAFs) are constituents of tumor microenvironments	[ { "docid": "6944800", "text": "Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.", "title": "Microenvironmental regulation of tumor progression and metastasis" } ]	[ { "docid": "952111", "text": "Cancer associated fibroblasts (CAFs) is one of the most crucial components of the tumor microenvironment which promotes the growth and invasion of cancer cells by various mechanisms. CAFs demonstrate a high degree of heterogeneity due to their various origins; however, many distinct morphological features and physiological functions of CAFs have been identified. It is becoming clear that the crosstalk between the cancer cells and the CAFs plays a key role in the progression of cancer, and understanding this mutual relationship would eventually enable us to treat cancer patients by targeting CAFs. In this review, we will discuss the latest findings on the role of CAFs in tumorigenesis and metastasis as well as potential therapeutic implication of CAFs.", "title": "Cancer associated fibroblasts (CAFs) in tumor microenvironment." }, { "docid": "32742683", "text": "Among cells present in the tumor microenvironment, activated fibroblasts termed cancer-associated fibroblasts (CAFs), play a critical role in the complex process of tumor-stroma interaction. CAFs, one of the prominent stromal cell populations in most types of human carcinomas, have been involved in tumor growth, angiogenesis, cancer stemness, extracellular matrix remodeling, tissue invasion, metastasis, and even chemoresistance. During the past decade, these activated tumor-associated fibroblasts have also been involved in the modulation of the anti-tumor immune response on various levels. In this review, we describe our current understanding of how CAFs accomplish this task as well as their potential therapeutic implications.", "title": "Alteration of the Antitumor Immune Response by Cancer-Associated Fibroblasts" }, { "docid": "8702697", "text": "AIMS Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-κB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination. RESULTS We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma. CONCLUSION The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease.", "title": "miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts." }, { "docid": "10812605", "text": "Fibroblasts regulate the structure and function of healthy tissues, participate transiently in tissue repair after acute inflammation, and assume an aberrant stimulatory role during chronic inflammatory states including cancer. Such cancer-associated fibroblasts (CAFs) modulate the tumor microenvironment and influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. These pleiotropic functions highlight the inherent plasticity of fibroblasts and may provide new avenues to understand and therapeutically intervene in malignancies. We discuss the emerging themes of CAF biology in the context of tumorigenesis and therapy.", "title": "Fibroblast heterogeneity in the cancer wound" }, { "docid": "35993767", "text": "Fibroblasts are rich in the surrounding microenvironment of hepatocellular carcinoma (HCC) because most HCCs occur in fibrotic or cirrhotic livers. However, the role of cancer-associated fibroblasts (CAFs) in HCC metastasis remains obscure. Here, we reported that CAFs promote the migration and invasion of HCC cells in vitro and facilitate the HCC metastasis to the bone, brain and lung in NOD/SCID mice. The RayBio human chemokine antibody array revealed that CAFs secret higher levels of CCL2, CCL5, CCL7 and CXCL16 than peri-tumor fibroblasts. CCL2 and CCL5 increase the migration but not the invasion of HCC cells, while CCL7 and CXCL16 promote both migration and invasion of HCC cells. Moreover, CCL2 and CCL5 stimulate the activation of the hedgehog (Hh) pathway, while CCL7 and CXCL16 enhance the activity of the transforming growth factor-β (TGF-β) pathway in HCC cells. The neutralizing antibodies of chemokines notably attenuate the effect of CAFs on HCC metastasis and compromised the activation of Hh and TGF-β pathways in HCC cells. In summary, CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells.", "title": "Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways." }, { "docid": "9648896", "text": "Lung cancer is the leading cause of cancer-related mortality in humans worldwide. Moreover, the overall 5-year survival rate is only 15%. Pathologically almost 80% of all lung cancer cases are non-small cell lung cancer (NSCLC). Cancer-associated fibroblasts (CAFs) have been found to exist in a large number of NSCLCs. CAFs have been proven to promote tumor progression, metastasis and resistance to therapy through paracrine effects in most solid tumors. In the present study, firstly we isolated CAFs from patient tissues and demonstrated that they promoted cell proliferation and chemoresistance to cisplatin in the lung cancer cell lines A549 and 95D in a paracrine manner. Secondly, using ELISA and quantative PCR, we found that a higher amount of stromal cell-derived factor 1 (SDF-1) existed in the CAFs rather than that observed in the normal fibroblasts (NFs). Thirdly, we detected that SDF-1 facilitated lung cancer cell proliferation and drug resistance via the CXCR4-mediated signaling pathway which involved NF-κB and Bcl-xL. Moreover, we also confirmed that the expression level of SDF-1 in the CAFs was negatively regulated by microRNA mir-1 through microRNA overexpression and quantitative PCR. Overall, our data provide one explanation for the effects of CAFs on lung cancer cells. Meanwhile, our results also suggest CAFs as a potential therapeutic target in tumor treatment.", "title": "mir-1-mediated paracrine effect of cancer-associated fibroblasts on lung cancer cell proliferation and chemoresistance." }, { "docid": "3559136", "text": "Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with a CXCR2 antagonist blocked granulocyte infiltration of tumors and showed strong anti-tumor effects.", "title": "Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors." }, { "docid": "1727493", "text": "Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer.", "title": "Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1" }, { "docid": "15832146", "text": "Fibroblasts often constitute the majority of the stromal cells within a breast carcinoma, yet the functional contributions of these cells to tumorigenesis are poorly understood. Using a coimplantation tumor xenograft model, we demonstrate that carcinoma-associated fibroblasts (CAFs) extracted from human breast carcinomas promote the growth of admixed breast carcinoma cells significantly more than do normal mammary fibroblasts derived from the same patients. The CAFs, which exhibit the traits of myofibroblasts, play a central role in promoting the growth of tumor cells through their ability to secrete stromal cell-derived factor 1 (SDF-1); CAFs promote angiogenesis by recruiting endothelial progenitor cells (EPCs) into carcinomas, an effect mediated in part by SDF-1. CAF-secreted SDF-1 also stimulates tumor growth directly, acting through the cognate receptor, CXCR4, which is expressed by carcinoma cells. Our findings indicate that fibroblasts within invasive breast carcinomas contribute to tumor promotion in large part through the secretion of SDF-1.", "title": "Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion" }, { "docid": "3727986", "text": "Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.", "title": "A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion" }, { "docid": "27647593", "text": "Cancer cells do not exist as pure homogeneous populations in vivo. Instead they are embedded in \"cancer cell nests\" that are surrounded by stromal cells, especially cancer associated fibroblasts. Thus, it is not unreasonable to suspect that stromal fibroblasts could influence the metabolism of adjacent cancer cells, and visa versa. In accordance with this idea, we have recently proposed that the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria. An in depth analysis of this phenomenon reveals that aggressive cancer cells are \"parasites\" that use oxidative stress as a \"weapon\" to extract nutrients from surrounding stromal cells. Oxidative stress in fibroblasts induces the autophagic destruction of mitochondria, by mitophagy. Then, stromal cells are forced to undergo aerobic glycolysis, and produce energy-rich nutrients (such as lactate and ketones) to \"feed\" cancer cells. This mechanism would allow cancer cells to seed anywhere, without blood vessels as a food source, as they could simply induce oxidative stress wherever they go, explaining how cancer cells survive during metastasis. We suggest that stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm \"The Autophagic Tumor Stroma Model of Cancer Metabolism\", or the \"Reverse Warburg Effect\". We also discuss how glutamine addiction (glutaminolysis) in cancer cells fits well with this new model, by promoting oxidative mitochondrial metabolism in aggressive cancer cells.", "title": "Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment." }, { "docid": "26735905", "text": "The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the epithelium are poorly understood. Here we show that p62 levels were reduced in the stroma of several tumors and that its loss in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism, resulting in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through the modulation of metabolism in the tumor stroma.", "title": "Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis." }, { "docid": "313403", "text": "The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells and infiltrating immune cells, which may inhibit or promote tumor growth and progression. The objectives of this retrospective study were to characterize the density of tumor-associated macrophages (TAMs) in breast cancer, and to correlate the density of TAMs with clinicopathological parameters. Paraffin-embedded specimens and clinicopathological data, including up to 5 years follow-up information, were obtained from 172 breast cancer patients. Immunohistochemical staining for CD68 (marker for macrophages) was performed and evaluated in a blinded fashion. We found that TAMs were significantly frequent in high histopathological grade breast cancer patients. Breast cancer patients with a high density of TAMs had significantly lower rates of disease-free survival and 5-year overall survival than patients with low density of TAMs. Furthermore, high-infiltration of TAMs indicated worse survival rate for patients with node-negative breast cancer. In conclusion, the number of TAMs in the tumor stroma is an independent predictor of survival time for breast cancer patients. High-infiltration of TAMs is a significant unfavorable prognostic factor for patients with invasive breast cancer and, as such, is a potentially useful prognostic marker for breast cancer.", "title": "High-Infiltration of Tumor-Associated Macrophages Predicts Unfavorable Clinical Outcome for Node-Negative Breast Cancer" }, { "docid": "3376731", "text": "Various factors and cellular components in the tumor microenvironment are key drivers associated with drug resistance in many cancers. Here, we analyzed the factors and molecular mechanisms involved in chemoresistance in patients with esophageal squamous cell carcinoma (ESCC). We found that interleukin 6 (IL6) derived mainly from cancer-associated fibroblasts played the most important role in chemoresistance by upregulating C-X-C motif chemokine receptor 7 (CXCR7) expression through signal transducer and activator of transcription 3/nuclear factor-κB pathway. CXCR7 knockdown resulted in the inhibition of IL6-induced proliferation and chemoresistance. In addition, CXCR7 silencing significantly decreased gene expression associated with stemness, chemoresistance and epithelial–mesenchymal transition and suppressed the proliferation ability of ESCC cells in three-dimensional culture systems and angiogenesis assay. In clinical samples, ESCC patients with high expression of CXCR7 and IL6 presented a significantly worse overall survival and progression-free survival upon receiving cisplatin after operation. These results suggest that the IL6–CXCR7 axis may provide a promising target for the treatment of ESCC.", "title": "IL6 derived from cancer-associated fibroblasts promotes chemoresistance via CXCR7 in esophageal squamous cell carcinoma" }, { "docid": "22712546", "text": "Over the past years, plenty of evidence has emerged illustrating how metabolism supports many aspects of cellular function and how metabolic reprogramming can drive cell differentiation and fate. Here, we present a method to assess the metabolic configuration of single cells within their native tissue microenvironment via the visualization and quantification of multiple enzymatic activities measured at saturating substrate conditions combined with subsequent cell type identification. After careful validation of the approach and to demonstrate its potential, we assessed the intracellular metabolic configuration of different human immune cell populations in healthy and tumor colon tissue. Additionally, we analyzed the intercellular metabolic relationship between cancer cells and cancer-associated fibroblasts in a breast cancer tissue array. This study demonstrates that the determination of metabolic configurations in single cells could be a powerful complementary tool for every researcher interested to study metabolic networks in situ.", "title": "Exploring Metabolic Configurations of Single Cells within Complex Tissue Microenvironments." }, { "docid": "4429118", "text": "The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.", "title": "Cancer-related inflammation" }, { "docid": "15727984", "text": "Non-small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed \"stromal cells\") that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenvironment alter the tumor cell secretome, including those proteins required for tumor growth and dissemination, and we developed an in vitro model to test this hypothesis. Coculturing a murine K-ras mutant lung adenocarcinoma cell line (LKR-13) with a murine lung stromal cell (macrophage, endothelial cell, or fibroblast) enhanced stromal cell migration, induced endothelial tube formation, increased LKR-13 cell proliferation, and regulated the secretion of proteins involved in angiogenesis, inflammation, cell proliferation, and epithelial-to-mesenchymal transition. Among these proteins, CXCL1 has been reported to promote NSCLC development, whereas interleukin-18 (IL-18) has an undefined role. Genetic and pharmacologic strategies to inhibit CXCL1 and IL-18 revealed that stromal cell migration, LKR-13 cell proliferation, and LKR-13 cell tumorigenicity required one or both of these proteins. We conclude that stromal cells enhanced LKR-13 cell tumorigenicity partly through their effects on the secretome of LKR-13 cells. Strategies to inhibit tumor/stromal cell interactions may be useful as therapeutic approaches in NSCLC patients.", "title": "Identification of secreted proteins that mediate cell-cell interactions in an in vitro model of the lung cancer microenvironment." }, { "docid": "24349992", "text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.", "title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells." }, { "docid": "6807122", "text": "Activated fibroblasts are associated with many different tumors. Myofibroblasts, activated fibroblasts, and perivascular mesenchymal cells such as pericytes play a role in cancer progression. Many studies suggest that myofibroblasts facilitate tumor growth and cancer progression. The source for myofibroblasts and other activated fibroblasts within the tumors is still debated. Although de novo activation of quiescent fibroblasts into alpha-smooth muscle actin (alpha SMA)-positive myofibroblasts is one likely source, epithelial to mesenchymal transition and bone marrow recruitment are also evolving as possible mechanisms for the emergence of a heterogeneous population of carcinoma-associated fibroblasts. Here, we show that transforming growth factor-beta1 could induce proliferating endothelial cells to undergo a phenotypic conversion into fibroblast-like cells. Such endothelial to mesenchymal transition (EndMT) is associated with the emergence of mesenchymal marker fibroblast-specific protein-1 (FSP1) and down-regulation of CD31/PECAM. Additionally, we show EndMT in tumors using the B16F10 melanoma model and the Rip-Tag2 spontaneous pancreatic carcinoma model. Crossing Tie2-Cre mice with R26Rosa-lox-Stop-lox-LacZ mice allows for irreversible tagging of endothelial cells. We provide unequivocal evidence for EndMT at the invasive front of the tumors in these transgenic mice. Collectively, our results show that EndMT is a unique mechanism for the accumulation of carcinoma-associated fibroblasts and suggest that antiangiogenic treatment of tumors may have a direct effect in decreasing activated fibroblasts that likely facilitate cancer progression.", "title": "Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts." }, { "docid": "13007205", "text": "Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion. Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided. Tumor-derived fibroblasts promoted higher levels of invasion than normal fibroblasts (p = 0.041). When IPC was related to genotype, higher levels of IPC were generated by tumor fibroblasts with the high-expressing MMP-3 5A/5A genotype compared with the 5A/6A and 6A/6A genotypes (p = 0.05 and 0.07, respectively), and this was associated with enhanced MMP-3 release. The functional importance of MMP-3 was demonstrated by enhanced invasion in the presence of recombinant MMP-3, whereas reduction occurred in the presence of a specific MMP-3 inhibitor. An inverse relationship was demonstrated between fibroblast IPC and the high-expressing MMP-1 genotype (p = 0.031), but no relationship was seen with MMP-9 SNP status. In contrast, normal fibroblasts showed no variation in IPC in relation to MMP genotype, with MMP-3 5A/5A fibroblasts exhibiting significantly lower levels of IPC than their tumor-derived counterparts (p = 0.04). This study has shown that tumor-derived fibroblasts exhibit higher levels of IPC than normal fibroblasts and that the MMP-3 5A/5A genotype contributes to this through enhanced MMP-3 release. Despite a high-expressing genotype, normal fibroblasts do not exhibit higher IPC or enhanced MMP release. This suggests that more complex changes occur in tumor-derived fibroblasts, enabling full expression of the MMP SNP genotype and these possibly are epigenetic in nature. The results do suggest that, in women with breast cancer, a high-expressing MMP-3 genotype may promote tumor progression more effectively.", "title": "Intrinsic genetic characteristics determine tumor-modifying capacity of fibroblasts: matrix metalloproteinase-3 5A/5A genotype enhances breast cancer cell invasion" }, { "docid": "9767444", "text": "Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy. These data indicate that the type I IFN response is required for effective in vivo antitumorigenic actions of the DNMTi 5-azacytidine (AZA). Through type I IFN signaling, AZA increases the numbers of CD45+ immune cells and the percentage of active CD8+ T and natural killer (NK) cells in the tumor microenvironment, while reducing tumor burden and extending survival. AZA also increases viral defense gene expression in both tumor and immune cells, and reduces the percentage of macrophages and myeloid-derived suppressor cells in the tumor microenvironment. The addition of an HDACi to AZA enhances the modulation of the immune microenvironment, specifically increasing T and NK cell activation and reducing macrophages over AZA treatment alone, while further increasing the survival of the mice. Finally, a triple combination of DNMTi/HDACi plus the immune checkpoint inhibitor α-PD-1 provides the best antitumor effect and longest overall survival, and may be an attractive candidate for future clinical trials in ovarian cancer.", "title": "Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden." }, { "docid": "8963413", "text": "PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy.", "title": "PD-L1 expression in human cancers and its association with clinical outcomes" }, { "docid": "52925737", "text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.", "title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration" }, { "docid": "7986878", "text": "We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation therapy and intetumumab in human cancer xenograft models in nude rats to assess effects on both tumor cells and the tumor microenvironment. Nude rats bearing human head and neck cancer and non-small cell lung cancer (NSCLC) xenografts were treated with intetumumab and fractionated local tumor radiotherapy. Effects on tumor growth and metastasis, blood perfusion, oxygenation, and gastrointestinal toxicity were studied. Intetumumab alone had a moderate effect on tumor growth. When combined with fractionated radiation therapy, intetumumab significantly inhibited tumor growth and produced a tumor response rate that was significantly better than with radiation therapy alone. Treatment with intetumumab also significantly reduced lung metastasis in the A549 NSCLC xenograft model. The oxygenation and blood perfusion in xenograft tumors measured by microbubble-enhanced ultrasound imaging were substantially increased after treatment with intetumumab. The combined use of intetumumab and radiation therapy reduced the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. Toxicity studies showed that treatment with intetumumab did not cause the histopathologic changes in the lungs and did not sensitize the sensitive gastrointestinal epithelium to the effect of radiation therapy. Intetumumab can potentiate the efficacy of fractionated radiation therapy in human cancer xenograft tumors in nude rats without increased toxicity.", "title": "Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats." }, { "docid": "23576165", "text": "Aerobic glycolysis, i.e., the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e., the \"reverse Warburg effect\". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.", "title": "Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication." }, { "docid": "19130782", "text": "Interferon-gamma (IFN-γ) is a pleiotropic molecule with associated antiproliferative, pro-apoptotic and antitumor mechanisms. This effector cytokine, often considered as a major effector of immunity, has been used in the treatment of several diseases, despite its adverse effects. Although broad evidence implicating IFN-γ in tumor immune surveillance, IFN-γ-based therapies undergoing clinical trials have been of limited success. In fact, recent reports suggested that it may also play a protumorigenic role, namely, through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, and upregulation of indoleamine 2,3-dioxygenase and of checkpoint inhibitors, as programmed cell-death ligand 1. However, the IFN-γ-mediated responses are still positively associated with patient's survival in several cancers. Consequently, major research efforts are required to understand the immune contexture in which IFN-γ induces its intricate and highly regulated effects in the tumor microenvironment. This review discusses the current knowledge on the pro- and antitumorigenic effects of IFN-γ as part of the complex immune response to cancer, highlighting the relevance to identify IFN-γ responsive patients for the improvement of therapies that exploit associated signaling pathways.", "title": "Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion" }, { "docid": "4583180", "text": "Conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets, along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification.", "title": "Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression." }, { "docid": "15335331", "text": "BACKGROUND Both tumor-associated macrophages (TAMs) and the epithelial to mesenchymal transition (EMT) of cancer cells play key roles in promoting tumor progression. However, whether TAMs could induce EMT in the progression of oral squamous cell carcinoma (OSCC) remains undefined. RESULTS Here we detected the expression of macrophages markers CD68 and CD163, epithelial marker E-cadherin and mesenchymal marker vimentin in 127 OSCC patients by using semi-quantitative immunohistochemistry. CD68 and CD163 expression was not confined to the infiltrating TAMs, but also detected in cancer cells. The high number of CD68-positive macrophages was correlated with poor overall survival. Meanwhile, the expression of CD163 both in macrophages and in cancer cells was associated with poor overall survival and had a significant prognostic impact in OSCC. Importantly, the expression of CD163 in cancer cells had a significant relationship with E-cadherin and vimentin. Furthermore, the incubation of TAMs conditioned medium resulted in a fibroblast-like appearance of cancer cells (HN4, HN6 and SCC9) together with the decreased/increased expression of E-cadherin/ vimentin, which were correlated with the enhanced ability of migration and invasion. CONCLUSIONS Our results indicate that TAMs could promote the EMT of cancer cells, thereby leading to the progression of oral cancer.", "title": "Tumor-associated macrophages correlate with the clinicopathological features and poor outcomes via inducing epithelial to mesenchymal transition in oral squamous cell carcinoma" }, { "docid": "25726838", "text": "The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17-producing cells are detected in cancer patients and tumor-bearing mice, the role of IL-17 in tumor development is controversial, and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17R-deficient mice. A defect in IFN-gammaR increased tumor growth, whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals. Further experiments showed that neutralization of IL-17 by Abs inhibited tumor growth in wild-type mice, whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration, whereas it reduced the infiltration of myeloid-derived suppressor cells (MDSCs) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSCs in tumors. Further analysis indicated that IL-17 was required for the development and tumor-promoting activity of MDSCs in tumor-bearing mice. These data demonstrate that IL-17-mediated responses promote tumor development through the induction of tumor-promoting microenvironments at tumor sites. IL-17-mediated regulation of MDSCs is a primary mechanism for its tumor-promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.", "title": "IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells." }, { "docid": "3419802", "text": "Most human cancers, including myeloma, are preceded by a precursor state. There is an unmet need for in vivo models to study the interaction of human preneoplastic cells in the bone marrow microenvironment with non-malignant cells. Here, we genetically humanized mice to permit the growth of primary human preneoplastic and malignant plasma cells together with non-malignant cells in vivo. Growth was largely restricted to the bone marrow, mirroring the pattern in patients with myeloma. Xenografts captured the genomic complexity of parental tumors and revealed additional somatic changes. Moreover, xenografts from patients with preneoplastic gammopathy showed progressive growth, suggesting that the clinical stability of these lesions may in part be due to growth controls extrinsic to tumor cells. These data demonstrate a new approach to investigate the entire spectrum of human plasma cell neoplasia and illustrate the utility of humanized models for understanding the functional diversity of human tumors.", "title": "Microenvironment-dependent growth of pre-neoplastic and malignant plasma cells in humanized mice" } ]
7656	How do I build wealth?	[ { "docid": "296799", "text": "\"You got some answers that essentially inform you that CEOs that have £200k written on their paysheet may in fact get much more. I'll take the opposite point of view and talk about people who (according to whatever definition) have a £200k/year income. How can they afford it Guess no 1: not all of them can (in the sense that it is quite possible to end up with negative net worth at £200k/year income - particularly if you immediately want to show off with brand new luxury cars, luxury holidays and a large house in a very representative region). Guess no 2: not all of the £200k/year CEOs are equally visible. There is a trade-off between going for wealth, large house, and luxury car. I deliberately ordered the three points according to increased display of \"\"wealth\"\". However, display of wealth usually comes at a cost (in a very monetary sense). And there are ways to get much display without having much wealth (see below: lease the car, also the mortgage on the house usually isn't displayed on the outside). You also need to take into account how long they are already building up wealth. I guess the typical CEO with £200k/year you're asking about did not just finish school and enter his work life in this position. It would be very interesting to see how income, accumulating wealth (and possibly \"\"displayed wealth\"\") correlate. My guess is that the correlation between income and accumulated wealth isn't that high, and the correlation between displayed and actual wealth is probably even lower. they possess luxury cars, large house and huge savings Are you sure these are the same managers? E.g. the ones with the huge savings are and the ones with the luxury cars? I'm asking particularly about the luxury cars, because such cars loose value very quickly and/or are often not owned by the driver but rather by the bank or leasing company. Which on the other hand offers the more savings-oriented CEO who is not that much interested in having a brand new luxury car the possibility to go for a one-year-old and save the rest. Knowing that, your CEO should be able to buy a one-year-old Mercedes SL 350 / year. Or a new one every 1 1/2 years (without building up savings or buying a house). However, building up wealth will be much faster with the CEO going for the one-year-old as the brand-new car option amounts to loosing ca. £20 - 30k within a year. An even-more-savings-oriented CEO who keeps his existing Mercedes 300 TD for another few years, thinking that this conservative choice of car will be trust-inspiring to the customers. Or goes for the SLK thinking that most people anyways don't know that the K between SL and SLK halves the price... However, if you just want to be seen with the car: after an initial payment of say £8-10k, you can get a decent SLK 350 (not the base model, either) at a monthly rate of ca. 600£/month or less than £7k/year. Note however, that this money does not count towards any kind of wealth, it's just renting a nice car. In other words: If driving the SLK 350 is your absolute goal, you could in theory have that with a net salary of £25k/year (according to your tax calculation, that should be somewhere around £35k / year gross), if you have the savings for the initial payment (being able to make the initial payment may also help convincin the leasing company that you're serious about it and able to pay your rates). There are also huge differences in value between large houses, compare e.g. these 2: And, last but not least, there is a decided one-way component in the timing of priorities here: it is much easier to go and get a luxury car when you have savings than first going for the luxury car and then trying to make up with the savings... I forgot to answer the question in the caption of your question: How do I build wealth By going on to live as if your income were only £50k (as far as that is compatible with your job) - I gather the median gross income in the UK is about £30k, so aiming at £50k leaves you a very comfortable budget for luxury spending. If you want to build up wealth faster, adjust that. In general, if you can manage to withhold much of any income increase from spending, that will help (trivial but powerful truth). From the leasing calculation you can conclude that you basically have no chance to show off your wealth by luxury cars. That is, you'd need to go for luxury cars that are completely incompatible with with building if you want to show your built up wealth by the car: there are too many people who even destroy their existing wealth in order to display luxury. At least if anyone is around who has either a correct idea what luxury cars cost (or don't cost) or will look that up in the internet. Also, people who know such things may also have the idea that the probability that such a car was downright paid (wealth) is small compared to the probability of meeting a leased or (mortgaged) car. Which means, the plan to show off doesn't work out that well with the people you'd want to impress. As for the other people: just a bit of display you can get far cheaper: If you really want to drive the SLK, rent it for an occasion (weekend) rather than for years. I met a sales manager who told me which rental cars they get when important customers from far east are visiting. The rest of the year they drive normal business cars. You may want to choose a rental company that doesn't write their name on the license plate. Apply the same ideas to the decision of buying a house. Think about what you want for yourself, and then look where you can get how much of that for how much money. Oh, and by the way: if I understand correctly, the average UK CEO wage is £120k, not £200k.\"", "title": "" }, { "docid": "159952", "text": "\"As others have stated, CEO's often make more than 200K, and when they do, they're compensated with stock options and other lucrative bonuses and deals that allow them to build wealth above and beyond the face value of their salary. However, remember that having wealth makes it easier to build further wealth. As Victor pointed out, having wealth allows you to increase your wealth in different kinds of investments. Also, it gives you access to more human capital, e.g. wealth management services at firms like Northern Trust, a greater ability to diversify into investments like hedge funds, more abilities to invest abroad through foreign trusts, etc. Also, you have to realize that wealthier people often pay a lower percentage in taxes than people who earn a salary. In the US, long-term capital gains are taxed at a much lower rate than income, so wealthy individuals who earn much of their money from long-term investments won't pay nearly as high a rate. In my case, my current salary places me at the top of the 25% tax bracket (in the US), but if I earned all of my income through long-term capital gains instead of salary, I would only pay around 15-20% in taxes. Plus, I could afford numerous tax accounting firms to help me find ways to pay fewer taxes. It's not altruism that causes CEOs like Steve Jobs and Mark Zuckerberg to take a $1 salary. This isn't directly related to CEOs, and I'm not leveling accusations of corruption against high net worth individuals, but I remember spending a few months in a small town in a country known for its corruption. The mayor had recently purchased a home worth the equivalent of several million dollars, on his annual civil servant salary of approximately $20K. One of the students asked him how he managed to afford such a sizable property, and he replied \"\"I live very frugally.\"\" This is probably a relatively rare case (I'm sure it depends on the country), but nevertheless, it illustrates another way that some people build wealth.\"", "title": "" }, { "docid": "82304", "text": "Many CEOs I have heard of earn a lot more than 200k. In fact a lot earn more than 1M and then get bonuses as well. Many wealthy people increase there wealth by investing in property, the stock market, businesses and other assets that will produce them good capital growth. Oh yeh, and luck usually has very little to do with their success.", "title": "" }, { "docid": "161068", "text": "Another possibility is that a lot of it is bought using borrowed money. Especially if much of your own money is in the stock market, it may be beneficial to take out a loan to buy something compared to selling other assets to raise the same amount of cash. Even going by the likely relatively conservative £200K/year before taxes, you are looking at a very nice house going for perhaps around 3-5 years' worth of pre-tax income. Let's say you have good contacts at the bank and can secure a loan for £500K at 3.5% interest (not at all unreasonable if you make half that before taxes in a single year and purchase something that can be used as collateral for the money borrowed; with a bit of negotiating, I wouldn't be surprised if one could push the interest rate even lower, and stock in a publicly traded company can also trivially be used as collateral). That's less than £1500/month in interest, before any applicable tax effects -- less than 10% of the before-tax income. And like @Victor wrote, I think it's reasonable to say that especially if the company is publicly traded, the CEO makes more than £200K/year. Given an income of £200K/year and assuming 30% taxes on that amount (the marginal tax would likely be higher, and this includes e.g. interest expense deductions), the money left over after taxes and interest payments on a £500K 3.5% debt is still about £10K/month. Even with a pretty rapid amortization schedule and even if the actual tax rate is higher, that leaves quite a bit of money to be socked away in savings and other investments.", "title": "" }, { "docid": "313186", "text": "Share options. If you get options on £200,000-worth of a company and then its share price increases five-fold then you make £800,000, which is often taxed more favourably than salary.", "title": "" }, { "docid": "229110", "text": "CEOs are compensated with stocks and options on top of their salary. Most is in the form of stocks and options. You may see them with a fancy car, but they don't necessarily possess the car, house, etc. They merely control it, which is nearly as good. You may lease it, or time share it. It might be owned by the company and provided as a perk. To earn a million, there are 4 ways: a job, self-employed, own a business, and invest. The fastest way is to own a business. The slowest way is a job or self-employed. Investing is medium. To learn more, read Rich Dad's Cashflow Quadrants.", "title": "" } ]	[ { "docid": "534988", "text": "\"Given that a poor person probably has much less to invest, how can odds be in their favor? To add to Lan's great answer, if one is \"\"poor\"\" because they don't have enough income to build wealth (invest), then there are only two ways to change the situation - earn more or spend less. Neither are easy but both are usually possible. One can take on side jobs, look for a better-paying career, etc. Cutting spending can also be hard but is generally easier than adding income. In general, wealth building is more about what you do with your income than about how much you make. Obviously the more you make, the easier it is, but just about anyone can build wealth if they spend less than they make. Once your NET income is high enough that you have investible income, THEN you can start building wealth. Unfortunately many people have piles of debts to clean up before they are able to get to that point. What could a small guy with $100 do to make himself not poor anymore, right? Just having $100 is not going to make you \"\"rich\"\". There is a practical limit to how much return you can make short of high-risk activities like gambling, lottery tickets, etc. (I have actually seen this as a justification for playing the lottery, which I disagree with but is an interesting point). If you just invest $100 at 25% per year (for illustration - traditional investments typically only make 10-12% on average), in 10 years you'll have about $931. If instead you invest $100 per month at 12% annualized, in 10 years you'll have over $23,000. Not that $23,000 makes you rich - the point is that regularly saving money is much more powerful than having money to start with.\"", "title": "" }, { "docid": "195113", "text": "\"I think you came up with a worthy Masters/PhD research project, it is a great question. This is in Australia so it is difficult for me to have complete perspective. However, I can speak about the US of A. To your first point relatively few people inherit their wealth. According to a brief web search about 38% of billionaires, and 20% of millionaires inherited their wealth. The rest are self-made. Again, in the US, income mobility is very common. Some act like high level earners are just born that way, but studies have shown that a great deal of income mobility exists. I personally know people that have grown up without indoor plumbing, and extremely poor but now earn in the top 5% of wage earners. Quid's points are valid. For example a Starbucks, new I-Phone, and a brake job on your car are somewhat catastrophic if your income is 50K/year, hurts if your income is 100K, and an inconvenience if you make 250K/year. These situations are normal and happen regularly. The first person may have to take a pay day loan to pay for these items, the second credit card interest, the third probably has the money in the bank. All of this exaggerates the effect of an \"\"emergency\"\" on one's net worth. To me there is also a chicken-and-egg effect in wealth building and income. How does one build wealth? By investing wisely, planning ahead, budgeting, delaying gratification, finding opportunities, etc... Now if you take those same skills to your workplace isn't it likely you will receive more responsibility, promotions and raises? I believe so. And this too exaggerates the effect on one's net worth. If investing helps you to earn more, then you will have more to invest. To me one of the untold stories of this graph is not just investing, but first building a stable financial base. Having a sufficient emergency fund, having enough and the right kind of insurance, keeping loans to a minimum. Without doing those things first investments might need to be withdrawn, often at an inopportune time, for emergency purposes. Thanks for asking this!\"", "title": "" }, { "docid": "469701", "text": "\"How on Earth could there not be racial inequality in a nation that was 99% ethnically homogenous for a couple thousand years, during its greatest imperial (wealth building) stretch. And only in the post-war era of e 20th century did it begin to have very significant ethnic minority groups. And those minorities were mostly poor and uneducated on arrival. By what magic would that wealth be equally distributed now, just a few decades later? And in what universe is wealth equality by race now to be expected? Doors were opened to other cultures. This is a good thing. But.. Was the plan to re divide the wealth of individuals upon doing so? Where was that written? The immigrant groups in the UK are largely Pakistani and Indian... And in more recent years, Middle Eastern. They came with vast cultural and educational differences. Not to mention challenges like higher rates of birth defects and genetic abnormalities, crime rates and massive cultural impediments to female career success. Why would wealth equality have happened, and how? It would be more \"\"shocking\"\" if there actually was racial wealth equality now.\"", "title": "" }, { "docid": "487861", "text": "You can't force a horse to eat carrots. You have to make him hungry... It's good that you're ready to start saving. The hardest part about building wealth is that most people live in denial. They think a bigger hat is wealth. That said, you need to get your husband excited about the idea of saving. If you're capable of sparking a little passion in him for saving then you'll see your wealth grow almost over night. So, how do you make someone excited about something as boring as saving? Great question. If you find a way, write a book. Honestly, I think it's different for everyone. For me it was like someone turned on a light. I was blind but then I saw. If he is a reader then I would suggest the following books in this order. If he makes it through those and has any argument at all against saving then write a book about him haha. Now I want to be clear, the other two answers above mine were also spot on. If you can't get him passionate about it then you need to take the initiative and start doing it yourself. I can't stress enough though that you both need to be engaged in order to do it quickly and efficiently. Good luck!", "title": "" }, { "docid": "33912", "text": "There isn't any place you can put $300 and turn it into significant passive income. What you need to do instead is manage the active (work) income that you have so that your money goes farther, freeing income up for reducing debt and investing. Investing $300 one time won't add up to much, but investing $100 a month will turn into wealth over time. Making a monthly budget is the key to managing your income. In the process, you'll find out where your income is going, and you can be intentional about how much you want to spend on different things in your life. You can allocate some of your income to paying down debt and investing, which is what you need to do to get ahead. For some general guidelines on what to do with your money first, read this question: Oversimplify it for me: the correct order of investing. For more specifics on creating a budget, eliminating debt, and building wealth, I recommend the book The Total Money Makeover by Dave Ramsey.", "title": "" }, { "docid": "70243", "text": "\"You can't get started investing. There are preliminary steps that must be taken prior to beginning to invest: Only once these things are complete can you think about investing. Doing so before hand will only likely lose money in the long run. Figure these steps will take about 2.5 years. So you are 2.5 years from investing. Read now: The Total Money Makeover. It is full of inspiring stories of people that were able to turn things around financially. This is good because it is easy to get discouraged and believe all kind of toxic beliefs about money: The little guy can't get ahead, I always will have a car payment, Its too late, etc... They are all false. Part of the book's resources are budgeting forms and hints on budgeting. Read later: John Bogle on Investing and Bogle on Mutual Funds One additional Item: About you calling yourself a \"\"dummy\"\". Building personal wealth is less about knowledge and more about behavior. The reason you don't have a positive net worth is because of how you behaved, not knowledge. Even sticking a small amount in a savings account each paycheck and not spending it would have allowed you to have a positive net worth at this point in your life. Only by changing behavior can you start to build wealth, investing is only a small component.\"", "title": "" }, { "docid": "313500", "text": "This is possible. In fact in the cases of debt settlement the collection companies typically issue a 1099 for the difference on what is owed and what is settled, making that taxable income. So the IRS sees it as income (in the US). However, this kind of dishonesty is not conducive to building long term wealth or wealth of significant means. As others have said this is fraud, but provided that one is truthful on the loan application, it would be impossible to prove. How can one prove that a person has no intention of paying a loan back? Doing this once or twice may ruin your ability to receive a loan for legitimate purposes for life.", "title": "" }, { "docid": "296771", "text": "I agree with what you're saying, that people aren't completely rational. But to build an entire system on their irrationality is ludicrous... At some point, they figure it out. This is exactly how things change and change dramatically. > They are far too worried about the day-in day-out running of their business to spend their time day-dreaming of how to hide away all of their money once they become rich. Yeah, but if they don't think they're going to get rich, they'll simply stop minding the day-to-day. I would, and if they figure out that they're going to be patsies to be sacrificed at the altar of wealth redistribution, they're going to stop. Already, people are awaking to the fact that college educations do not bring them prosperity.", "title": "" }, { "docid": "139953", "text": "> The demand for fiat currencies comes from the fact they are necessary to pay taxes Only because the collective population has decided that the fiat currency has value. Taxes are not handed down by some benevolent leader, it is you and I deciding that we can do better things if we pool a portion of our wealth together. Let's say we want to build a road between our homes to improve the act of visiting each other. We decide to share the cost of building the road. I throw in 10 chicken, and you toss in 100 seashells. We work our way over to our road-building friend's place. We give him our offering in exchange for building the road. He doesn't like seashells, but he is willing to take 20 chickens in exchange for building the road. But now we are 10 chickens short from reaching our goal of having a new road between our homes. We decide to implement a strict agreement that all future pooling of wealth needs to be done with chickens. Seashells are not acceptable. And now we have a tax paid by a mutually agreed upon exchange medium. It works because everyone agrees that chickens have value. If everyone suddenly became vegetarian and saw chickens as having no value, our tax pool would become worthless. The fact that our tax is paid for in chickens does not mean that chickens will forever have value.", "title": "" }, { "docid": "454287", "text": "\"None of what I say is advice directed to you. It is how I would continue to analyse the situation you have, were it mine. First off, I prefer to work in certainties more than possibilities. Saying that, paying down the mortgage makes sense as I can calculate the amount I will save. I also believe that rate rises are coming in the future, based on the talk from the BofE, so any money I pay off now means guaranteed less interest to pay in the future. Also, the lower my loan-to-value ratio, the better/lower interest rates I can receive in the mortgage market. If I do not want to work until retirement age, it'd be nice to have as few bills as possible in the decade or so prior to retirement age. I could then do early-retirement or part-time work in the run-up to retirement. I could use my savings to fund life until retirement pays out. I'd be aiming to put 15% of my gross income into \"\"future investing\"\" - using ISAs to build up a savings pot, taking advantage of retirement products. That way all the money is not tied to a normal retirement age before it can accessed. And it's not touchable by future greedy Government taxation... Any income leftover above the 15%, I'd be throwing at the mortgage - taking advantage of the 10% overpay window, remortgaging as LTV comes down. In theory, overpaid mortgage equity is money that could still be accessed (provided house prices don't decline and remortgaging is a possibility). So, in short, I'd follow a plan along these lines of logic. 1) Make sure I have 4-6 months of living expenses as a Rainy Day Fund. Insulate myself from fluctuations in my financial situation. 2) Put away 15% of annual gross income towards \"\"future saving\"\". ISAs first, pension second. 3) Overpay the mortgage and look to remortgage as LTV drops. When LTV nears 60%, look to lock in to a longer-term fix. eg. 2 year fixes at 90% LTV, 5 year fixes at 60%. 4) Reassess steps 2 & 3 as life happens, circumstances change, work fluctuates, etc. 5) Once the mortgage is paid off, build as much wealth as possible - ISAs first, then non-tax efficient savings products. Aim for keeping expenses down and raising my savings % rate as much as possible. [Your analysis was thorough and shows you are thinking through consequences. Never forget to factor in the risk of carrying debt. Having no/low debt as you get older means there's more income left to build wealth. Ignore the American view of carrying debt for life and trusting investments to outperform the debt. You have to pay monthly to keep that debt around - and it ain't a pet!]\"", "title": "" }, { "docid": "57168", "text": "You cannot have off-campus employment in your first year, but investments are considered passive income no matter how much time you put into that effort. Obviously you need to stay enrolled full-time and get good enough grades to stay in good standing academically, so you should be cautious about how much time you spend day trading. If the foreign market is also active in a separate time zone, that may help you not to miss class or otherwise divert your attention from your investment in your own education. I have no idea about your wealth, but it seems to me that completing your degree is more likely to build your wealth than your stock market trades, otherwise you would have stayed home and continued trading instead of attending school in another country.", "title": "" }, { "docid": "396933", "text": "I would say you are typical. The way people are able to build their available credit, then subsequently build their average balances is buy building their credit score. According to FICO your credit score is made up as follows: Given that you had no history, and only new credit you are pretty much lacking in all areas. What the typical person does, is get a card, pay on it for 6 months and assuming good history will either get an automatic bump; or, they can request a credit limit increase. Credit score has nothing to do with wealth or income. So even if you had 100K in the bank you would likely still be facing the same issue. The bank that holds the money might make an exception. It is very easy to see how a college student can build to 2000 or more. They start out with a $200 balance to a department store and in about 6 months they get a real CC with a 500 balance and one to a second department store. Given at least a decent payment history, that limit could easily increase above 2500 and there could be more then one card open. Along the lines of what littleadv says, the companies even welcome some late payments. The fees are more lucrative and they can bump the interest rate. All is good as long as the payments are made. Getting students and children involved with credit cards is a goal of the industry. They can obtain an emotional attachment that goes beyond good business reasoning.", "title": "" }, { "docid": "244004", "text": "If you are looking to build wealth, leasing is a bad idea. But so is buying a new car. All cars lose value once you buy them. New cars lose anywhere between 30-60% of their value in the first 4 years of ownership. Buying a good quality, used car is the way to go if you are looking to build wealth. And keeping the car for a while is also desirable. Re-leasing every three years is no way to build wealth. The American Car Payment is probably the biggest factor holding many people back from building wealth. Don't fall into the trap - buy a used car and drive it for as long as you can until the maintenance gets too pricey. Then upgrade to a better used car, etc. If you cannot buy a car outright with cash, you cannot afford it. Period.", "title": "" }, { "docid": "283917", "text": "Its not a scam. The car dealership does not care how you pay for the car, just that you pay. If you come to them for a loan they will try and service you. If you come with cash, they will sell you a car and not try to talk you into financing. If you come with a check from another bank, they will happily accept it. I would try to work with Equifax or a local credit union to figure out what is going on. Somehow she probably had her credit frozen. Here are some really good things to mitigate this situation: Oh and make sure you do #1 and forget about financing cars ever again. I mean if you want to build wealth.", "title": "" }, { "docid": "458740", "text": "Don't be too scared of investing in the market. It has ups and downs, but over the long haul you make money in it. You can't jump in and out, just consistently add money to investments that you 1) understand and 2) trust. When I say understand, what I mean is you can follow how the money is generated, either because a company sells products, a government promises to pay back the bond, or compounding interest makes sense. You don't need to worry about the day to day details, but if you don't understand how the money is made, it isn't transparent enough and a danger could be afoot. Here are some basic rules I try (!) to follow The biggest trick is to invest what you can, and do so consistently. You can build wealth by earning more and spending less. I personally find spending less a lot easier, but earning more is pretty easy with some simple investment tools.", "title": "" }, { "docid": "475668", "text": "For reference see this article. This article does an okay job of explaining why, but it could be better. To expand on point #4 if you lose your job, you will be forced to repay the loan in 90 days. If do not pay it back in time, you will be hit with your highest marginal tax rate and a 10% penalty. How does borrowing money at 40% interest sound? Why do you have credit card debt? I'll give you the loving answer: bad behavior. The longer you hold this debt the more indicative it is about out of control behavior. To remedy this I would recommend the following: While you are behaving like most people (normal); most people are broke. Congratulations on having the desire to not be broke. Do you now have the courage to change? Having that courage could mean generational wealth building and freedom from debt. As a reformed overspender it has meant exactly that for me and my family.", "title": "" }, { "docid": "304641", "text": "\"Fred is correct ... MOST financial advisors (but not all) are paid either for managing your assets or for selling you financial products. But success at anything, especially building wealth, is all about PROCESS, not products. I applaud your desire to find a financial advisor to help you because this is not something that most people have the education, experience or capacity to do themselves (it is impossible to get the perspective you need to make the best choices). Start with a CERTIFIED FINANCIAL PLANNER professional - they have an ethical duty to do what is in your best interests ahead of their own (the \"\"fiduciary standard\"\"). You might interview two or three. Work with the one who is transparent about how they are paid and whose process is focused on helping you achieve your goals ... not following any rule of thumb or standard boilerplate. Your goals are different. Your financial life is different. Find someone who can help YOU follow YOUR agenda ... not their own.\"", "title": "" }, { "docid": "99658", "text": "\"I think the answer to how much you \"\"should\"\" spend depends on a few more questions: Once you answer these questions I think you'll have a better idea of what you should spend. If you have no financial goals then what kind of car you buy doesn't really matter. But if your goals are to build and accumulate wealth both in the short and long term then you should know that, by the numbers, a car is terrible financial investment. A new car loses thousands of dollars in value the moment you drive it off the lot. Buy the cheapest, reliable commuter you can ($5k or less) and use the extra money to pay off your debts. Then once your debts are paid off start investing that money. If you continue this frugal mindset with your other purchases (what house to buy, what food to eat, what indulgences to indulge in, etc...) and invest a bit, I think you'll find it pretty easy to create a giant amount of wealth.\"", "title": "" }, { "docid": "345403", "text": "\"Congratulations. The first savings goal should be an emergency fund. Think of this not as an investment, but as insurance against life's woes. They happen and having this kind of money earmarked allows one to invest without needing to withdraw at an inopportune time. This should go into a \"\"high interest\"\" savings account or money market account. Figure three to six months of expenses. The next goal should be retirement savings. In the US this is typically done through 401K or if your company does not offer one, either a ROTH IRA or Traditional IRA. The goal should be about 15% of your income. You should favor a 401k match over just about anything else, and then a ROTH over that. The key to transforming from a broke college student into a person with a real job, and disposable income, is a budget. Otherwise you might just end up as a broke person with a real job (not fun). Part of your budget should include savings, spending, and giving. All three areas are the key to building wealth. Once you have all of those taking care of the real fun begins. That is you have an emergency fund, you are putting 15% to retirement, you are spending some on yourself, and giving to a charity of your choice. Then you can dream some with any money left over (after expenses of course). Do you want to retire early? Invest more for retirement. Looking to buy a home or own a bunch of rental property? Start educating yourself and invest for that. Are you passionate about a certain charity? Give more and save some money to take time off in order to volunteer for that charity. All that and more can be yours. Budgeting is a key concept, and the younger you start the easier it gets. While the financiers will disagree with me, you cannot really invest if you are borrowing money. Keep debt to zero or just on a primary residence. I can tell you from personal experience that I did not started building wealth until I made a firm commitment to being out of debt. Buy cars for cash and never pay credit card interest. Pay off student loans as soon as possible. For some reason the idea of giving to charity invokes rancor. A cursory study of millionaires will indicate some surprising facts: most of them are self made, most of them behave differently than pop culture, and among other things most of them are generous givers. Building wealth is about behavior. Giving to charity is part of that behavior. Its my own theory that giving does almost no good for the recipient, but a great amount of good for the giver. This may seem difficult to believe, but I ask that you try it.\"", "title": "" }, { "docid": "385932", "text": "\"*(\"\"Fee-only\"\" meaning the only money they make is the fee your folks pay directly; no kickbacks from financial products they're selling.) The answer to this is: for God's sake, leave it alone! I commend you on wanting to help your family avoid more losses. You are right, that having most of one's retirement in one stock or sector is just silly. And again yes, if they're retired, they probably need some bonds. But here's the thing, if they follow your advise and it doesn't work out, it will be a SERIOUS strain on your relationship. Of course you'll still be a family and they'll still love you, but emotionally, you are the reason they lost the money, and that will an elephant in between you. This is especially the case since we're talking about a lot of money here (presumably), and retirement money to boot. You must understand the risk you're taking with your relationships. If you/they lose, at best it'll make things awkward, and you'll feel guilty about their impoverished retirement. At worst it can destroy your relationship with your folks. What about if you win? Won't you be feted and appreciated by your folks for saving them from themselves? Yes, for a short while. Then life moves on. Everything returns to normal. But here's the thing. You won't win. You can't. Because even if you're right here, and they win, that means both they and you will be eager for you to do it again. And at some point they'll take a hit based on your advise. Can I be blunt here? You didn't even know that you can't avoid capital gains taxes by reinvesting stock gains. You don't know enough, and worse, you're not experienced enough. I deduce you're either a college student, or a recent grad. Which means you don't have experience investing your own money. You don't know how the market moves, you just know the theory. You know who you are? You're me, 20 years ago. And thank God my grandparents ignored my advise. I was right about their utilities stocks back then, too. But I know from what I learned in the years afterwards, investing on my own account, that at some point I would have hurt them. And I would have had a very hard time living with that. So, tell your folks to go visit a fee-only financial adviser to create a retirement plan. Perhaps I'm reading into your post, but it seems like you're enthusiastic about investing; stocks, bonds, building wealth, etc. I love that. My advise -- go for it! Pull some money together, and open your own stock account. Do some trading! As much as people grouse about it, the market really is glorious. It's like playing Monopoly, but for keeps. I mean that in the best way possible. It's fun, you can build wealth doing it, and it provides a very useful social purpose. In the spirit of that, check out these ideas (just for you, not for your folks!), based on ideas in your post: Good luck.\"", "title": "" }, { "docid": "25859", "text": "Youre assuming that GDP shows the amount of wealth created and is an indicator of the standard of living, but it is not. Govt spending adds to gdp but takes away from the productive capabiliies of the private sector, which is the part of the economy that is making things that people want and need. The govt can spend 1 trillion on building a monument to obama, and that would increase gdp by 1 trillion, but no wealth is created and the govt jut shift a trillion of tax revenues to the workers who built the monument. If a company spends 1 trillion building building some new gadget, then the people who spend money to buy i have something to show for it and the workers have their wages as well. So now the company makes back 1.2 trillion and the consumers have their gadget, ie real wealth has been created. The wealthy may be sittin on hoards of cash, but its not just sitting under their mattress. Its spread out between investments and savings. Savings is neccessary to build up productive capabilities. The money the rich have sitting in banks is being used to help other businesses grow, not just collecting dust. I wish it were as simple as giving every poor person 10 grand and watching the economy take off, remember when bush gave everyone a 1000 tax refund? It sure was fun blowing that on a ps3, i cant argue with that. But prosperity can not be printed, it must be earned through hard work and productive activity. What we need is not monetary stimulus, we need the govt to stop destimulating the private sector with burdensome regulations and taxes. We need lower barriers to entry so we maximize competition in every industry. We need the govt spending less, and pushing more workers into the private sector, making things that american can get some utility from. Its not going to be a smooth ride getting there, there will be lots of lay offs in the short run as the economy restructures. But if the govt got out of the way and let the free market prosper, our society would be far better off in the future", "title": "" }, { "docid": "386803", "text": "Investing money in the stock market with [Compound Stock Earnings](http://www.compoundstockearnings.com) is a great way to build wealth and plan for the future. However, few people know what the stock market is let alone how to begin investing in it. It is important to understand how companies and stocks work before investing in them.", "title": "" }, { "docid": "298514", "text": "I dont see anything dystopian about this? Half the article is about new millionaires being created by 2021. That is a good thing isnt it? I know reddit is all about forcing millionaires to sell their stocks and real estate so Starbucks baristas and people folding shirts at the mall can make $50/hr and drive Mercedes though. How dare rich people own stock when the stock market doubles!!! The audacity of them to manage their money wisely and work hard to build their wealth.", "title": "" }, { "docid": "589607", "text": "I think the strongest reason against DHA purchases (I don't consider them investments) is points 3 and 5 mentioned above. The resale market is only to other investors that are convinced its a good investment.If you can't sell to owner occupiers, you've just removed the MAJORITY of your potential pool of people to resell to - this has a devastating effect on your ability to make any capital gain from your investment - if you're not chasing capital gain...be sure to understand why! (see article below)The marketing people will have you believe that DHA is a great investment from a yield perspective...maybe so, I haven't crunched the numbers. But in my opinion, I would wonder - who cares?Yield is important to ensure you can hold the property, but if there is no capital growth and you can't sell it for a profit or release some equity to buy the next investment, then you've just put a massive road block in your wealth building path.I am at the asset accumulation phase of my investing journey, so my opinion is skewed towards capital growth investments. Unless you have a sizable equity base already, in my opinion $4-5 Million in debt free assets, then you should be looking for capital growth assets...not high yield.This article from Your Investment Property magazine, although now dated, gives a good example to illustrate my point on why capital growth is the sensible strategy during the asset building phase of your wealth creation journey: Why capital growth is still king I think the strongest reason against DHA purchases (I don't consider them investments) is points 3 and 5 mentioned above. The resale market is only to other investors that are convinced its a good investment. If you can't sell to owner occupiers, you've just removed the MAJORITY of your potential pool of people to resell to - this has a devastating effect on your ability to make any capital gain from your investment - if you're not chasing capital gain...be sure to understand why! (see article below) The marketing people will have you believe that DHA is a great investment from a yield perspective...maybe so, I haven't crunched the numbers. But in my opinion, I would wonder - who cares? Yield is important to ensure you can hold the property, but if there is no capital growth and you can't sell it for a profit or release some equity to buy the next investment, then you've just put a massive road block in your wealth building path. I am at the asset accumulation phase of my investing journey, so my opinion is skewed towards capital growth investments. Unless you have a sizable equity base already, in my opinion $4-5 Million in debt free assets, then you should be looking for capital growth assets...not high yield. This article from Your Investment Property magazine, although now dated, gives a good example to illustrate my point on why capital growth is the sensible strategy during the asset building phase of your wealth creation journey: Why capital growth is still king", "title": "" }, { "docid": "436150", "text": "\"As an entrepreneur, I have nothing against ambitious people working hard to become rich. I do however have a problem with people who want to hear bad economic news on hopes the central banks will pump money into it and push the markets up. I get even more pissed seeing these undeserving pricks get rich when their dreams come true. I am not saying the stock market is a bad thing. But if you get rich why not start a business and build real wealth then maybe invest a little in it? Why depend on the stock market as a primary means of generating wealth? Some of these people are like parasitic traitors hoping for everyone else to suffer so they can get rich off of them (notice I said \"\"some\"\" not \"\"all.\"\" edit:if you are going to downvote me at least have the balls to tell me what you disagree with. Maybe I'm saying something stupid and being a dick. I admit it's happened before but at least call me out instead of being passive-aggressive about it.\"", "title": "" }, { "docid": "495774", "text": "I am sorry for your loss, this person blessed you greatly. For now I would put it in a savings account. I'd use a high yield account like EverBank or Personal Savings from Amex. There are others it is pretty easy to do your own research. Expect to earn around 2200 if you keep it there a year. As you grieve, I'd ask myself what this person would want me to do with the money. I'd arrive at a plan that involved me investing some, giving some, and spending some. I have a feeling, knowing that you have done pretty well for yourself financially, that this person would want you to spend some money on yourself. It is important to honor their memory. Giving is an important part of building wealth, and so is investing. Perhaps you can give/purchase a bench or part of a walkway at one of your favorite locations like a zoo. This will help you remember this person fondly. For the investing part, I would recommend contacting a company like Fidelity or Vanguard. The can guide you into mutual funds that suit your needs and will help you understand the workings of them. As far as Fidelity, they will tend to guide you toward their company funds, but they are no load. Once you learn how to use the website, it is pretty easy to pick your own funds. And always, you can come back here with more questions.", "title": "" }, { "docid": "248962", "text": "\"What is your biggest wealth building tool? Income. If you \"\"nerf\"\" your income with payments to banks, cable, credit card debt, car payments, and lattes then you are naturally handicapping your wealth building. It is sort of like trying to drive home a nail holding a hammer right underneath the head. Normal is broke, don't be normal. Normal obtains student loans while getting an education. You don't have to. You can work part time, or even full time and get a degree. As an example, here is one way to do it in Florida. Get a job working fast food and get your associates degree using a community college that are cheap. Then apply for the state troopers. Go away for about 5 months, earning an income the whole time. You automatically graduate with a job that pays for state schools. Take the next three years (or more if you want an advanced degree) to get your bachelors. Then start your desirable career. What is better to have \"\"wasted\"\" approx 1.5 years being a state trooper, or to have a student loan payment for 20 years? There is not even pressure to obtain employment right after graduation. BTW, I know someone who is doing exactly what I outlined. Every commercial you watch is geared toward getting you to sign on the line that is dotted, often going into debt to do so. Car commercials will tell you that you are a bad mom or not a real man if you don't drive the 2015 whatever. Think differently, throw out your numbers and shoot for zero debt. EDIT: OP, I have a MS in Comp Sci, and started one in finance. My wife also has a masters. We had debt. We paid that crap off. Work like a fiend and do the same. My wife's was significant. She planned on having her employer pay it off for each year she worked there. (Like 20% each year or something.) Guess what, that did not work out! She went to work somewhere else! Live like you are still in college and use all that extra money to get rid of your debt. Student loans are consumer debt.\"", "title": "" }, { "docid": "480773", "text": "Overall, I strongly recommend cashing out your savings and becoming debt free today, and then never borrowing again except for a house. Advantages: Disadvantages: My wife and I paid of all of my grad school debt last year, and we’re paying off all of her grad school debt this year. To pay that aggressively, we’ve had to learn to live on a much tighter budget. But when we’re done, if we simply invest what we have been paying toward debt into the stock market, our nest egg will compound to over $10 million by the time we retire. According to Dave Ramsey, when the Forbes 400 were polled, 75% of them cited becoming and staying debt-free as the single best way to build wealth: http://www.daveramsey.com/article/three-steps-to-wealth-building-for-young-adults/lifeandmoney_college/text4/", "title": "" }, { "docid": "149081", "text": "I think it's because there are people who build entire wealth-gain strategies around certain conditions. When those conditions change, their mechanism of gaining wealth is threatened and they may take a short term loss as they transform their holdings to a new strategy.", "title": "" }, { "docid": "230612", "text": "\"No you should not borrow money at 44.9%. I would recommend not borrowing money except for a home with a healthy deposit (called down payment outside UK). in December 2016, i had financial crisis So that was like 12 days ago. You make it sound like the crisis was a total random event, that you did nothing to cause it. Financial crises are rarely without fault. Common causes are failure to understand risk, borrowing too much, insuring too little, improper maintenance, improper reserves, improper planning, etc... Taking a good step or two back and really understanding the cause of your financial crisis and how it could be avoided in the future is very useful. Talk to someone who is actually wealthy about how you could have behaved differently to avoid the \"\"crisis\"\". There are some small set of crises that are no fault of your own. However in those cases the recipe to recovery is patience. Attempting to recover in 12 days is a recipe for further disaster. Your willingness to consider borrowing at 44% suggests this crisis was self-inflicted. It also indicates you need a whole lot more education in personal finance. This is reinforced by your insatiable desire for a high credit score. Credit score is no indication of wealth, and is meaningless until you desire to borrow money. From what I read, you should not be borrowing money. When the time comes for you to buy a home with a mortgage, its fairly easy to have a high enough credit score to borrow at a good rate. You get there by paying your bills on time and having a sufficient deposit. Don't chase a high credit score at the expense of building real wealth.\"", "title": "" } ]
PLAIN-1492	LDL cholesterol	[ { "docid": "MED-3253", "text": "OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.", "title": "Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis." }, { "docid": "MED-2846", "text": "OBJECTIVE: A cross-sectional institutional-based study was undertaken to know the prevalence of Gestational Diabetes Mellitus (GDM) among Indian pregnant women. SUBJECTS AND METHODS: 325 pregnant women were screened for evidence of diabetes who were previously not known to be diabetic. They underwent 75 g, 2 hour, oral glucose tolerance test (OGTT). Chi-square test was done for statistically association of variables in GDM. RESULTS AND CONCLUSIONS: The results of this study indicate that bad obstetrics history, obese patient on high calorie diet especially non vegetarian diet with less physical activity are highly prone to develop GDM.", "title": "A hospital based study of prevalence of gestational diabetes mellitus in an urban population of India." }, { "docid": "MED-4033", "text": "Saturated fatty acids (SFAs) produce an inflammatory response. Hyperinflammation is now recognized as one of the key underlying etiologic factors in periodontal disease. The longitudinal relationship between dietary SFAs and periodontal disease in 264 Japanese individuals, aged 75 years, for whom data were available for the years 2003-2004, was investigated. SFA intake was assessed with a brief self-administered diet history questionnaire. Participants were classified by quartiles of SFA intake. Full-mouth periodontal status, measured as the clinical attachment level (CAL), was recorded at baseline and follow-up examinations. The number of teeth with a loss of CAL≥3 mm at any site over a year was calculated as 'periodontal disease events'. Poisson regression analysis was conducted, with dietary SFAs as the primary predictor of interest, to estimate their influence on periodontal disease events. High dietary SFA intake was significantly associated with a greater number of periodontal disease events among non-smokers. The multivariate adjusted relative risk (95% confidence intervals) in the 1st, 2nd, 3rd, and 4th quartiles of dietary SFAs was 1.00, 1.19 (0.72-1.97), 1.55 (0.95-2.52), and 1.92 (1.19-3.11), respectively. These findings suggest an independent association of dietary SFA intake to the progression of periodontal disease in older Japanese non-smokers. ABBREVIATIONS: saturated fatty acid (SFA); clinical attachment level (CAL); Toll-like receptor (TLR); lipopolysaccharide (LPS); brief self-administered diet history questionnaire (BDHQ); decayed, missing, and filled teeth (DMFT); clinical attachment level (CAL); body mass index (BMI); relative risk (RR); confidence intervals (CI); nuclear factor-kappa B (NF-κB).", "title": "Relationship between saturated fatty acids and periodontal disease." }, { "docid": "MED-1253", "text": "OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19", "title": "Effects of soy as tofu vs meat on lipoprotein concentrations." }, { "docid": "MED-3432", "text": "Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.", "title": "Mediterranean diet improves erectile function in subjects with the metabolic syndrome." }, { "docid": "MED-4324", "text": "BACKGROUND: Increasingly the potential harm from high cholesterol intake, and specifically from egg yolks, is considered insignificant. We therefore assessed total plaque area (TPA) in patients attending Canadian vascular prevention clinics to determine if the atherosclerosis burden, as a marker of arterial damage, was related to egg intake. To provide perspective on the magnitude of the effect, we also analysed the effect of smoking (pack-years). METHODS: Consecutive patients attending vascular prevention clinics at University Hospital had baseline measurement of TPA by duplex ultrasound, and filled out questionnaires regarding their lifestyle and medications, including pack-years of smoking, and the number of egg yolks consumed per week times the number of years consumed (egg-yolk years). RESULTS: Data were available in 1262 patients; mean (SD) age was 61.5 (14.8) years; 47% were women. Carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and with egg-yolk years. Plaque area in patients consuming <2 eggs per week (n = 388) was 125 ± 129 mm(2), versus 132 ± 142 mm(2) in those consuming 3 or more eggs per week (n = 603); (p < 0.0001 after adjustment for age). In multiple regression, egg-yolk years remained significant after adjusting for coronary risk factors. INTERPRETATION: Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease. This hypothesis should be tested in a prospective study with more detailed information about diet, and other possible confounders such as exercise and waist circumference. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Egg yolk consumption and carotid plaque." }, { "docid": "MED-1252", "text": "The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol, 218 to 307 mg/dl. The diets were low in cholesterol, 200 mg/day, with 13 to 16% of energy as protein, 30 to 35% as fat, and a polyunsaturated to saturated fat ratio of 0.5. Of protein 65% was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats. Fresh egg yolk was added to balance the cholesterol content of the diets. Proteins from grains and vegetables were identical in both menus and contributed about 35% of dietary protein. Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol. Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups. Mean decreases in plasma cholesterol, 16 and 13%, for responders in the animal and soy groups were significant, p less than 0.01 and 0.05, respectively. Responders in both groups had higher initial plasma cholesterol values than nonresponders. Although plasma high-density lipoprotein cholesterol decreased slightly, the high-density lipoprotein cholesterol to cholesterol ratio (high-density lipoprotein cholesterol/total cholesterol) remained constant for most individuals. The hypocholesterolemic effects were similar for both animal and soy protein (p less than 0.05) and fat (p less than 0.05) while on the experimental diet. All groups significantly decreased dietary cholesterol (p less than 0.001).", "title": "Determinants of hypocholesterolemic response to soy and animal protein-based diets." }, { "docid": "MED-3820", "text": "BACKGROUND: A single high-fat meal induces endothelial activation, which is associated with increased serum concentrations of inflammatory cytokines. OBJECTIVE: We compared the effect of 3 different meals on circulating concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin in healthy subjects and in patients with type 2 diabetes mellitus. DESIGN: Thirty patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h after ingestion of the meals. RESULTS: Compared with nondiabetic subjects, diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01) concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In both nondiabetic and diabetic subjects, IL-18 concentrations increased and adiponectin concentrations decreased (P < 0.05) from baseline concentrations after consumption of the high-fat meal. After consumption of the high-carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic patients. IL-8 concentrations did not change significantly after consumption of any of the 3 meals. CONCLUSIONS: This study provides evidence that circulating IL-18 and adiponectin concentrations are modulated by familiar foodstuffs in humans. Meal modulation of cytokines involved in atherogenesis may represent a safe strategy for ameliorating atherogenetic inflammatory activity in diabetic patients.", "title": "Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus." }, { "docid": "MED-2597", "text": "Since the beginning of the 1990s, increasing evidence supports beneficial effects of nut consumption on health. A new analysis of the Spanish PREDIMED trial, published in BMC Medicine, has expanded our knowledge. The study showed that individuals eating nuts more than three times per week died less often from cardiovascular disease and cancer than non-consumers. The study also adds an important finding that previous epidemiological studies could not provide: a protective effect on premature mortality was only seen in the intervention group in which nut consumption increased during the 4.8 years of follow-up, not in the intervention group with additional olive oil consumption or in the control group. Nut consumption actually decreased during follow-up in the latter two groups. Questions remain to be answered on the quantity of nuts to be consumed for health benefits, on possible mechanisms of action, and on whether some types of nuts should be favored. Please see related research: http://www.biomedcentral.com/1741-7015/11/164.", "title": "Should we go nuts about nuts?" }, { "docid": "MED-3201", "text": "Background Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Methods Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. Results The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). Conclusions These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. Trial registration ClinicalTrials.gov NCT00581074", "title": "Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults" }, { "docid": "MED-3202", "text": "1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3-demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.", "title": "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man." }, { "docid": "MED-5013", "text": "INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish \"nasi-lemak\", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) (\"McDonald's\") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.", "title": "Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake." }, { "docid": "MED-2847", "text": "BACKGROUND: Women with gestational diabetes are at increased risk of developing type 2 diabetes, but the risk and time of onset have not been fully quantified. We therefore did a comprehensive systematic review and meta-analysis to assess the strength of association between these conditions and the effect of factors that might modify the risk. METHODS: We identified cohort studies in which women who had developed type 2 diabetes after gestational diabetes were followed up between Jan 1, 1960, and Jan 31, 2009, from Embase and Medline. 205 relevant reports were hand searched. We selected 20 studies that included 675 455 women and 10 859 type 2 diabetic events. We calculated and pooled unadjusted relative risks (RRs) with 95% CIs for each study using a random-effects model. Subgroups analysed were the number of cases of type 2 diabetes, ethnic origin, duration of follow-up, maternal age, body-mass index, and diagnostic criteria. FINDINGS: Women with gestational diabetes had an increased risk of developing type 2 diabetes compared with those who had a normoglycaemic pregnancy (RR 7.43, 95% CI 4.79-11.51). Although the largest study (659 164 women; 9502 cases of type 2 diabetes) had the largest RR (12.6, 95% CI 12.15-13.19), RRs were generally consistent among the subgroups assessed. INTERPRETATION: Increased awareness of the magnitude and timing of the risk of type 2 diabetes after gestational diabetes among patients and clinicians could provide an opportunity to test and use dietary, lifestyle, and pharmacological interventions that might prevent or delay the onset of type 2 diabetes in affected women. FUNDING: None.", "title": "Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis." }, { "docid": "MED-2894", "text": "AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.", "title": "Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma." }, { "docid": "MED-2428", "text": "This paper is based on a longer report on the benefits, safety and modalities of information representation with regard to women and statin use, situated within the historical context of Women's Health Movement which has advocated for unbiased, appropriate medical research and prescribing for women based on the goals of full-disclosure, informed consent, evidence-based medicine and gender-based analysis. The evidence base for prescribing statins for women, especially for primary prevention is weak, yet Canadian data suggest that half of all prescriptions are for women. Safety meta-analyses do not disaggregate for women; do not consider female vulnerability to statin induced muscle problems, and women-centred concerns such as breast-cancer, miscarriage or birth defects are under-researched. Many trials have not published their non-cardiac serious adverse event data. These factors suggest that the standards of full-disclosure, informed consent, evidence-based prescribing and gender-based analysis are not being met and women should proceed with caution.", "title": "Women and statin use: a women's health advocacy perspective." }, { "docid": "MED-2181", "text": "Background Little is known about the impact of location of food consumption and preparation upon daily energy intake for children. Objective To examine trends in daily energy intake by children for foods eaten at home or away-from-home, by source of preparation, and for combined categories of eating location and food source. Subjects The analysis uses data from 29,217 children aged 2–18 years from the 1977–1978 Nationwide Food Consumption Survey, 1989–1991 and 1994–1998 Continuing Survey of Food Intake by Individuals, and 2003–2006 National Health and Nutrition Examination Surveys. Methods Nationally representative weighted percentages and means of daily energy intake by eating location were analyzed for trends from 1977 to 2006. Comparisons by food source were examined from 1994 to 2006. Analyses were repeated for 3 age groups: 2–6, 7–12, and 13–18 year olds. Difference testing was conducted using a t test. Results Increased energy intake (+179 kcal/d) by children from 1977–2006 was associated with a major increase in calories eaten away-from-home (+255 kcal/d). The percentage of kcal/d eaten away-from-home increased from 23.4% to 33.9% from 1977–2006. No further increase was observed from 1994–2006, but the sources of calories shifted. The percentage of calories from fast food increased to surpass intake from schools and become the largest contributor to foods prepared away-from-home for all age groups. For foods eaten away-from-home, the percentage of kcal/d from stores increased to become the largest source of calories eaten away-from-home. Fast food eaten at home and store-bought food eaten away-from-home increased significantly. Conclusion Eating location and food source significantly impact daily energy intake for children. Foods prepared away-from-home, including fast food eaten at home and store-prepared food eaten away-from-home, are fueling the increase in total calorie intake. However, further research using alternative data sources is necessary to verify that store-bought foods eaten away-from-home are increasingly store-prepared.", "title": "Trends in energy intake among US children by eating location and food source, 1977–2006" }, { "docid": "MED-4005", "text": "The aim of the present study was to examine the effect of a single high-fat meal with different fat quality on circulating inflammatory markers and gene expression in peripheral blood mononuclear cells (PBMC) to elucidate the role of fat quality on postprandial inflammation. A postprandial study with fourteen healthy females consuming three test meals with different fat quality was performed. Test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analysed. The test meal consisted of three cakes enriched with coconut fat (43 % energy as saturated fat and 1 % energy as α-linolenic acid (ALA)), linseed oil (14 % energy as ALA and 30 % energy as saturated fat) and cod liver oil (5 % energy as EPA and DHA and 5 % energy as ALA in addition to 31 % energy as saturated fat). In addition, ex vivo PBMC experiments were performed in eight healthy subjects investigating the effects of EPA and ALA on release and gene expression of inflammatory markers. The IL-8 mRNA level was significantly increased after intake of the cod liver oil cake at 6 h compared with fasting level, which was significantly different from the effect observed after the intake of linseed cake. In contrast, no effect was seen on circulating level of IL-8. In addition, ALA and EPA were shown to elicit different effects on the release and mRNA expression levels of inflammatory markers in PBMC cultured ex vivo, with EPA having the most prominent pro-inflammatory potential.", "title": "Effect of the fat composition of a single high-fat meal on inflammatory markers in healthy young women." }, { "docid": "MED-4353", "text": "We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.", "title": "Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol." }, { "docid": "MED-1923", "text": "Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Loving-Kindness Meditation practice associated with longer telomeres in women." }, { "docid": "MED-5015", "text": "Medical resources routinely used for intravenous hydration and resuscitation of critically ill patients may be limited in remote regions of the world. When faced with these shortages, physicians have had to improvise with the available resources, or simply do without. We report the successful use of coconut water as a short-term intravenous hydration fluid for a Solomon Island patient, a laboratory analysis of the local coconuts, and a review of previously documented intravenous coconut use.", "title": "The intravenous use of coconut water." }, { "docid": "MED-2843", "text": "BACKGROUND: The risk of major congenital malformations (MCM) is increased in women with pregestational diabetes mellitus (PGDM). Whether this risk is increased in gestational diabetes mellitus (GDM) is still debated. The aim of this study was to perform a systematic review (and meta-analysis) of major congenital malformations in women with gestational diabetes versus a reference population. METHODS: We conducted a MEDLINE search (1 January 1995 to 31 December 2009) of original studies reporting data on major congenital malformations in women with gestational diabetes and a reference group. Information on pregestational diabetes was collected when available. Two investigators considered studies for inclusion and extracted data; discrepancies were solved by consensus. Meta-analysis tools were used to summarize results. MOOSE and PRISMA guidelines were followed. RESULTS: Two case control and 15 cohort studies were selected out of 3488 retrieved abstracts. A higher risk of major congenital malformations was observed in offspring of women with gestational diabetes with the following relative risk (RR)/odds ratios (OR) and 95% confidence intervals (CI): RR 1.16 (1.07-1.25) in cohort studies and OR 1.4 (1.22-1.62) in case control studies. Risk of major congenital malformations was much higher in offspring of women with PGDM than in those of the reference group: RR 2.66 (2.04-3.47) in cohort studies and OR 4.7 (3.01-6.95) in the single case control study providing information. CONCLUSION: There is a slightly higher risk of major congenital malformations in women with gestational diabetes than in the reference group. The contribution of women with overt hyperglycemia and other factors could not be ascertained. This risk, however, is much lower than in women with pregestational diabetes. Copyright © 2011 John Wiley & Sons, Ltd.", "title": "Major congenital malformations in women with gestational diabetes mellitus: a systematic review and meta-analysis." }, { "docid": "MED-1555", "text": "The confounding that results from the uncontrolled conditions under which most epidemiologic observations are made is sufficient to undermine their validity with respect to investigation of the relationship between diet and serum cholesterol. In this paper, the authors show, using both a mathematical model and referring to empirical data, that if certain variances are sufficiently great, even when there is cause and effect, correlation coefficients close to zero would be expected from the actual data of a cross-sectional study. Cross-sectional designs are therefore not suitable for studying this relationship.", "title": "Diet and serum cholesterol: do zero correlations negate the relationship?" }, { "docid": "MED-4027", "text": "Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.", "title": "Dietary behavior and knowledge of dental erosion among Chinese adults" }, { "docid": "MED-4543", "text": "Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.", "title": "Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o..." }, { "docid": "MED-2891", "text": "BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.", "title": "Variations in product choices of frequently purchased herbs: caveat emptor." }, { "docid": "MED-5116", "text": "BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.", "title": "Dietary flavonoid intake and breast cancer survival among women on Long Island." }, { "docid": "MED-2502", "text": "Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.", "title": "Macronutrient balance and lifespan" }, { "docid": "MED-4035", "text": "The aim of the present in situ study was to evaluate the effect of different periods of intra-oral remineralisation on the susceptibility of softened dentin to toothbrushing abrasion. Groups of 6 human dentin specimens (A-F) were recessed in the buccal aspects of intra-oral appliances which were worn for 21 days by 11 volunteers. The samples were demineralised twice a day extra-orally in the acidic beverage Sprite Light (pH 2.9) for 90 s. Subsequently, the dentin specimens were brushed at different times. Specimen A was brushed immediately after demineralisation. Specimens B-E were brushed after the intra-oral appliances had been worn for various periods in the mouth: specimen B for 10 min, C for 20 min, D for 30 min and E for 60 min. Specimen F was not brushed (control). After 21 days, dentin wear was measured with a profilometer. The following values (means +/- standard deviation) were recorded (microm): A, 23.6 +/- 16.7; B, 37.9 +/- 29.7; C, 31.8 +/- 26.5; D, 18.5 +/- 10.5; E, 15.3 +/- 11.6; F, 12.6 +/- 6.7. There was a statistically significantly increased dentin loss for groups A, B and C as compared to the controls (U test: p < 0.05). However, after intra-oral periods of 30 and 60 min, wear was not significantly higher than in unbrushed controls. It is concluded that for protection of dentin surfaces at least 30 min should elapse before toothbrushing after an erosive attack. Copyright 2004 S. Karger AG, Basel", "title": "Brushing abrasion of softened and remineralised dentin: an in situ study." }, { "docid": "MED-2378", "text": "Background Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. Objective To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). Design Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). Results The ALA and LA diets significantly reduced diastolic blood pressure (−2 to −3 mm Hg) and total peripheral resistance (−4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. Conclusions These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.", "title": "Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function" }, { "docid": "MED-2441", "text": "Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.", "title": "Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocy..." }, { "docid": "MED-3422", "text": "In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.", "title": "Mediterranean diet improves sexual function in women with the metabolic syndrome." }, { "docid": "MED-2082", "text": "BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..." }, { "docid": "MED-2431", "text": "Background Mechanistic studies largely support the chemopreventive potential of statins. However, results of epidemiologic studies investigating statin use and breast cancer risk have been inconsistent and lacked the ability to evaluate long-term statin use. Materials and Methods We utilized data from a population-based case-control study of breast cancer conducted in the Seattle-Puget Sound region to investigate the relationship between long-term statin use and breast cancer risk. 916 invasive ductal carcinoma (IDC) and 1,068 invasive lobular carcinoma (ILC) cases 55-74 years of age diagnosed between 2000 and 2008 were compared to 902 control women. All participants were interviewed in-person and data on hypercholesterolemia and all episodes of lipid lowering medication use were collected through a structured questionnaire. We assessed the relationship between statin use and IDC and ILC risk using polytomous logistic regression. Results Current users of statins for 10 years or longer had a 1.83-fold increased risk of IDC [95% confidence interval (CI): 1.14-2.93] and a 1.97-fold increased risk of ILC (95% CI: 1.25-3.12) compared to never users of statins. Among women diagnosed with hypercholesterolemia, current users of statins for 10 years or longer had more than double the risk of both IDC [odds ratio (OR): 2.04, 95% CI: 1.17-3.57] and ILC (OR: 2.43, 95% CI: 1.40-4.21) compared to never users. Conclusion In this contemporary population-based case-control study long-term use of statins was associated with increased risks of both IDC and ILC. Impact Additional studies with similarly high frequencies of statin use for various durations are needed to confirm this novel finding.", "title": "Long-term statin use and risk of ductal and lobular breast cancer among women 55-74 years of age" }, { "docid": "MED-3139", "text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.", "title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women" }, { "docid": "MED-3129", "text": "BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.", "title": "BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression." }, { "docid": "MED-3817", "text": "Background: Putrescine, spermidine, and spermine are the polyamines required for human cell growth. The inhibition of ornithine decarboxylase (ODC), which is the rate-limiting enzyme of polyamine biosynthesis, decreases tumor growth and the development of colorectal adenomas. A database was developed to estimate dietary polyamine exposure and relate exposure to health outcomes. Objective: We hypothesized that high polyamine intake would increase risk of colorectal adenoma and that the allelic variation at ODC G>A +316 would modify the association. Design: Polyamine exposure was estimated in subjects pooled (n = 1164) from the control arms of 2 randomized trials for colorectal adenoma prevention [Wheat Bran Fiber low-fiber diet arm (n = 585) and Ursodeoxycholic Acid placebo arm (n = 579)] by using baseline food-frequency questionnaire data. All subjects had to have a diagnosis of colorectal adenoma to be eligible for the trial. Results: A dietary intake of polyamines above the median amount in the study population was associated with 39% increased risk of colorectal adenoma at follow-up (adjusted OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample. In addition, younger participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48, 4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had significantly increased odds of colorectal adenoma if they consumed above-median polyamine amounts. Conclusions: This study showed a role for dietary polyamines in colorectal adenoma risk. Corroboration of these findings would confirm a previously unrecognized, modifiable dietary risk factor for colorectal adenoma.", "title": "Dietary polyamine intake and risk of colorectal adenomatous polyps" }, { "docid": "MED-3249", "text": "144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.", "title": "Effect of low saturated fat diet in early and late cases of multiple sclerosis." }, { "docid": "MED-4539", "text": "This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a \"natural product mimic\" or \"NM\" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than \"S\" (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the \"host from whence it was isolated\", and therefore we consider that this area of natural product research should be expanded significantly.", "title": "Natural products as sources of new drugs over the last 25 years." }, { "docid": "MED-2215", "text": "We investigated the relationship between animal product consumption and evidence of dementia in two cohort substudies. The first enrolled 272 California residents matched for age, sex, and zip code (1 vegan, 1 lacto-ovo-vegetarian, and 2 'heavy' meat eaters in each of 68 quartets). This design ensured a wide range of dietary exposure. The second included 2,984 unmatched subjects who resided within the Loma Linda, California area. All subjects were enrolled in the Adventist Health Study. The matched subjects who ate meat (including poultry and fish) were more than twice as likely to become demented as their vegetarian counterparts (relative risk 2.18, p = 0.065) and the discrepancy was further widened (relative risk 2.99, p = 0.048) when past meat consumption was taken into account. There was no significant difference in the incidence of dementia in the vegetarian versus meat-eating unmatched subjects. There was no obvious explanation for the difference between the two substudies, although the power of the unmatched sub-study to detect an effect of 'heavy' meat consumption was unexpectedly limited. There was a trend towards delayed onset of dementia in vegetarians in both substudies.", "title": "The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study." }, { "docid": "MED-1553", "text": "Although consumers say they are concerned about nutrition and are aware that eating a healthful diet is important for good health, this knowledge does not always translate into healthful diet behaviors or motivate behavior change. In an effort to better understand consumer attitudes about nutrition and to explore alternatives for communicating dietary advice in language that is meaningful and motivates behavior change, the International Food Information Council (IFIC) conducted qualitative research with consumers (using focus groups) and registered dietitians (using telephone interviews) in 1998 and 1999. Results of the research are presented using dietary fat as a case study. Findings from the IFIC research were reported to the Dietary Guidelines Advisory Committee to assist the Committee in developing meaningful and action-oriented dietary advice related to dietary fat for inclusion in the 2000 Dietary Guidelines for Americans that would be motivating and easy for consumers to implement. The recommendation to moderate fat intake in the new dietary guideline, \"Choose a diet that is low in saturated fat and cholesterol and moderate in total fat\" is consistent with communication recommendations in the IFIC research. Further, the moderate fat message is empowering because it suggests an achievable dietary regimen and reduces guilt and worry about foods. It allows flexibility to enjoy desired foods and promotes using common sense when it comes to diet. Several issues emerged from the IFIC research that apply to general nutrition communications with consumers, whether it be through national nutrition recommendations or in one-on-one counseling situations: to be effective, messages to consumers about nutrition, and specifically dietary fat, must address sources of discomfort about dietary choices; they must engender a sense of empowerment; and they should motivate both by providing clear information that propels toward taking action and appeals to the need to make personal choices.", "title": "Developing actionable dietary guidance messages: dietary fat as a case study." }, { "docid": "MED-4087", "text": "Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.", "title": "Fibromyalgia and nutrition, what do we know?" }, { "docid": "MED-2511", "text": "Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \"functional foods\" and, indeed, are currently being explored for their potential health-enhancing properties.", "title": "The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load." }, { "docid": "MED-3906", "text": "Date palm is one of the oldest trees cultivated by man. In the folk-lore, date fruits have been ascribed to have many medicinal properties when consumed either alone or in combination with other herbs. Although, fruit of the date palm served as the staple food for millions of people around the world for several centuries, studies on the health benefits are inadequate and hardly recognized as a healthy food by the health professionals and the public. In recent years, an explosion of interest in the numerous health benefits of dates had led to many in vitro and animal studies as well as the identification and quantification of various classes of phytochemicals. On the basis of available documentation in the literature on the nutritional and phytochemical composition, it is apparent that the date fruits are highly nutritious and may have several potential health benefits. Although dates are sugar-packed, many date varieties are low GI diet and refutes the dogma that dates are similar to candies and regular consumption would develop chronic diseases. More investigations in these areas would validate its beneficial effects, mechanisms of actions, and fully appreciate as a potential medicinal food for humans all around the world. Therefore, in this review we summarize the phytochemical composition, nutritional significance, and potential health benefits of date fruit consumption and discuss its great potential as a medicinal food for a number of diseases inflicting human beings.", "title": "Date fruits (Phoenix dactylifera Linn): an emerging medicinal food." }, { "docid": "MED-1616", "text": "The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.", "title": "Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials." }, { "docid": "MED-2430", "text": "The objective of this study was to investigate the effects of the dietary phytosterol beta-sitosterol (SIT) and the antiestrogen drug tamoxifen (TAM) on cell growth and ceramide (CER) metabolism in MCF-7 and MDA-MB-231 human breast cancer cells. The MCF-7 and MDA-MB-231 cell lines were studied as models of estrogen receptor positive and estrogen receptor negative breast cancer cells. Growth of both cell lines as determined using the sulforhodamine B assay was inhibited by treatment with 16 microM SIT but only MCF-7 cell growth was inhibited by treatment with 1 microM TAM. The combination of SIT and TAM further inhibited growth in both cell lines, most significantly in MDA-MB-231 cells. CER is a proapoptotic signal and CER levels were increased in both MCF-7 and MDA-MB-231 cells by individual treatment with SIT and TAM and the combined treatment raised cellular CER content even further. SIT and TAM raised CER levels by different means. SIT potently activated de novo CER synthesis in both MCF-7 and MDA-MB-231 cells by stimulating serine palmitoyltransferase activity; whereas TAM promoted CER accumulation in both cell types by inhibiting CER glycosylation. These results suggest that the combination regimen of dietary SIT and TAM chemotherapy may be beneficial in the management of breast cancer patients.", "title": "beta-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by affecting ceramide metabolism." }, { "docid": "MED-4846", "text": "The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.", "title": "Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis." }, { "docid": "MED-4556", "text": "Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.", "title": "Tolerable upper intake levels for trans fat, saturated fat, and cholesterol." }, { "docid": "MED-2845", "text": "OBJECTIVE: Epidemiological studies suggest that high body iron stores are associated with insulin resistance and type 2 diabetes. The aim of this study was to evaluate the association between dietary intake of iron and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study within the Nurses' Health Study. We followed 85,031 healthy women aged 34-59 years from 1980 to 2000. Dietary data were collected every 4 years, and data on medical history and lifestyle factors were updated biennially. RESULTS: During the 20 years of follow-up, we documented 4,599 incident cases of type 2 diabetes. We found no association between total, dietary, supplemental, or nonheme iron and the risk of type 2 diabetes. However, heme iron intake (derived from animal products) was positively associated with risk; relative risks (RRs) across increasing quintiles of cumulative intake were 1.00, 1.08 (95% CI 0.97-1.19), 1.20 (1.09-1.33), 1.27 (1.14-1.41), and 1.28 (1.14-1.45) (P(trend) < 0.0001) after controlling for age, BMI, and other nondietary and dietary risk factors. In addition, when we modeled heme iron in seven categories, the multivariate RR comparing women who consumed > or =2.25 mg/day and those with intake <0.75 mg/day was 1.52 (1.22-1.88). The association between heme iron and the risk of diabetes was significant in both overweight and lean women. CONCLUSIONS: This large cohort study suggests that higher heme iron intake is associated with a significantly increased risk of type 2 diabetes.", "title": "Iron intake and the risk of type 2 diabetes in women: a prospective cohort study." }, { "docid": "MED-2591", "text": "Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v. 1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 = 1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95 % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.", "title": "Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular ..." }, { "docid": "MED-2943", "text": "BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.", "title": "Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk." }, { "docid": "MED-2694", "text": "Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.", "title": "Pathological aspects of lipid peroxidation." }, { "docid": "MED-3255", "text": "BACKGROUND: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. METHODS AND RESULTS: Between 1990 and 1992, we randomized healthy 7-month-old infants (n=1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (P=0.0034) but not in girls (P=0.69). The maximum endothelium-dependent dilation response (mean+/-SD) was 9.62+/-3.53% and 8.36+/-3.85% in intervention boys and control boys and 8.84+/-4.00% and 8.44+/-3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted means: 9.46% [CI 8.68% to 10.24%] versus 8.54% [CI 7.75% to 9.32%], P=0.11). CONCLUSIONS: A low-saturated-fat diet introduced in infancy and maintained during the first decade of life is associated with enhanced endothelial function in boys. The effect is explained in part by the diet-induced reduction in serum cholesterol concentration.", "title": "Endothelial function in healthy 11-year-old children after dietary intervention with onset in infancy: the Special Turku Coronary Risk Factor Inter..." }, { "docid": "MED-1915", "text": "Background Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells. Methods We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30–64. Work-related exhaustion was assessed using the Maslach Burnout Inventory - General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR) -based method. Results After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016) than those with no exhaustion (p = 0.009). The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008). Conclusions These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.", "title": "Work-Related Exhaustion and Telomere Length: A Population-Based Study" }, { "docid": "MED-3822", "text": "Only a limited number of studies on cellulite have been published in the international literature and many of them reach somewhat antithetical conclusions. Consequently, it is not yet possible to reconcile the extreme differences of opinion which have lingered on for years concerning the nature of this disorder, as well as its origin and even the most basic aspects of its histopathological classification. It does not even have a recognized name: in fact, the term 'cellulitis' is used in scientific English to indicate a spreading gangrenous infection of the subcutaneous cellular tissue. The other terms used from time to time [panniculitis, lipodystrophy, edematofibrosclerotic panniculitis (EFP), liposclerosis, lipoedema, etc.] have quite different morphological and pathogenetic connotations in general. Over the last few decades, three major conflicting theories have emerged in relation to the ethiopathogenesis of cellulite. These indicate, respectively, the following causes: 1. Oedema caused by excessive hydrophilia of the intercellular matrix. 2. A homeostatic alteration on a regional microcirculatory level; this pathogenetic theory is summarized in a synthetic and self-explanatory denomination: EFP. 3. A peculiar anatomical conformation of the subcutaneous tissue of women, different from male morphology. These theories must all now be updated in the light of recent advances on the sophisticated and composite physiopathology of the adipose organ - which acts not only as a control device which regulates the systematic equilibrium of energy and modulates the food intake and the metabolism of other tissue substrate through a multiple glandular secretion of hormones and parahormones.", "title": "Cellulite: nature and aetiopathogenesis." }, { "docid": "MED-4024", "text": "We reviewed data from six cohort studies and approximately 40 case-control studies on the relation between selected aspects of diet and the risk of oral and pharyngeal cancer. Fruit and vegetables were inversely related to the risk: the pooled relative risk (RR) for high vegetable consumption was 0.65 from three cohort studies on upper aerodigestive tract cancers and 0.52 from 18 case-control studies of oral and pharyngeal cancer; corresponding RRs for high fruit consumption were 0.78 and 0.55. beta-carotene, vitamin C and selected flavonoids have been inversely related to the risk, but it is difficult to disentangle their potential effect from that of fruit and vegetables. Whole grain, but not refined grain, intake was also favorably related to oral cancer risk. The results were not consistent with reference to other foods beverages, and nutrients, but it is now possible to exclude a strong relation between these foods and oral and pharyngeal cancer risk. In western countries, selected aspects of diet may account for 20-25% of oral and pharyngeal cancer, and the population attributable risk increases to 85-95% when tobacco and alcohol consumption are also considered.", "title": "Dietary factors and oral and pharyngeal cancer risk." }, { "docid": "MED-2182", "text": "Over the past century, a major shift in North American food practices has been taking place. However, the literature on this topic is lacking in several areas. Some available research on food and cooking practices in the current context is presented, with a focus on how these are affecting health and how they might be contributing to health inequalities within the population. First, cooking and cooking skills are examined, along with the ambiguities related to terms associated with cooking in the research literature. Food choice, cooking, and health are described, particularly in relation to economic factors that may lead to health inequalities within the population. The importance of developing an understanding of factors within the wider food system as part of food choice and cooking skills is presented, and gaps in the research literature are examined and areas for future research are presented. Cooking practices are not well studied but are important to an understanding of human nutritional health as it relates to cultural, environmental, and economic factors.", "title": "Food, cooking skills, and health: a literature review." }, { "docid": "MED-2381", "text": "The inverse association of nut consumption and risk markers of coronary heart disease (lipids) has sparked the interest of the scientific and lay community. The objective of this study was to conduct a systematic review to investigate the effects of nuts on the lipid profile. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. Human intervention trials with the objective of investigating independent effects of nuts on lipid concentrations were included. From the literature search, 415 publications were screened and 23 studies were included. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The results of 3 almond (50-100 g/d), 2 peanut (35-68 g/d), 1 pecan nut (72 g/d), and 4 walnut (40-84 g/d) studies showed decreases in total cholesterol between 2 and 16% and LDL cholesterol between 2 and 19% compared with subjects consuming control diets. Consumption of macadamia nuts (50-100 g/d) produced less convincing results. In conclusion, consumption of approximately 50-100 g (approximately 1.5-3.5 servings) of nuts > or = 5 times/wk as part of a heart-healthy diet with total fat content (high in mono- and/or polyunsaturated fatty acids) of approximately 35% of energy may significantly decrease total cholesterol and LDL cholesterol in normo- and hyperlipidemic individuals.", "title": "A systematic review of the effects of nuts on blood lipid profiles in humans." }, { "docid": "MED-3398", "text": "Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.", "title": "Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction." }, { "docid": "MED-2705", "text": "Atherosclerosis may result partly from processes that occur following food consumption and that involve oxidized lipids in chylomicrons. We investigated reactions that could occur in the acidic pH of the stomach and accelerate the generation of lipid hydroperoxides and co-oxidation of dietary constituents. The ability of dietary polyphenols to invert catalysis from pro-oxidation to antioxidation was examined. The acidic pH of gastric fluid amplified lipid peroxidation catalyzed by metmyoglobin or iron ions. Metmyoglobin catalyzed peroxidation of edible oil, resulting in 8-fold increase of hydroperoxide concentration. The incubation of heated muscle tissue in simulated gastric fluid for 2 h enhanced hydroperoxides accumulation by 6-fold to 1200 microM. In the presence of catechin or red wine polyphenols, metmyoglobin catalyzed the breakdown of hydroperoxides to zero, totally preventing lipid peroxidation and beta-carotene cooxidation. We suggest that human gastric fluid may be an excellent medium for enhancing the oxidation of lipids and other dietary constituents. The results indicate the potentially harmful effects of oxidized fats intake in the presence of endogenous catalysts found in foods, and the major benefit of including in the meal plant dietary antioxidants.", "title": "The stomach as a bioreactor: dietary lipid peroxidation in the gastric fluid and the effects of plant-derived antioxidants." }, { "docid": "MED-2370", "text": "In this third installment of the series, we point out that the absence of an explicit, detailed and plausible hypothesis linking hypercholesterolemia to the events in the artery wall was probably an important reason for continuing skepticism and for failure to treat elevated blood cholesterol levels. The rapid advances in understanding of lipoprotein metabolism in the 1950s and 1960s and the application of modern cellular biology in the 1970s provided the context for a modern consensus on pathogenetic mechanisms of atherogenesis.", "title": "Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defi..." }, { "docid": "MED-3001", "text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").", "title": "Towards a new system of health: the challenge of Western disease." }, { "docid": "MED-3203", "text": "The contents of the bioactive compounds in red and blond grapefruits and their influence on humans suffering from hypertriglyceridemia were studied. It was found that red grapefruit has a higher content of bioactive compounds and a higher antioxidant potential than blond grapefruit, determined by oxygen radical scavenging capacity, 1,1-diphenyl-2-picrylhydrazyl, carotenoid bleaching, and Folin-Ciocalteu assays. Fifty-seven hyperlipidemic patients, ages 39-72 years, after coronary bypass surgery, recruited from the Institute's pool of volunteers, were randomly divided into three equal in number (19) groups: two experimental (red and blond groups) and one control group (CG). During 30 consecutive days of the investigation the diets of the patients of the red and blond dietary groups were daily supplemented with one equal in weight fresh red or blond grapefruit, respectively. Before and after this trial, serum lipid levels of all fractions and serum antioxidant activity were determined. It was found that serum lipid levels in patients of the red and blond groups versus the CG after treatment were decreased: (a) total cholesterol, 6.69 versus 7.92 mmol/L, 15.5%, and 7.32 versus 7.92 mmol/L, 7.6%, respectively; (b) low-density lipoprotein cholesterol, 5.01 versus 6.29 mmol/L, 20.3%, and 5.62 versus 6.29 mmol/L, 10.7%, respectively; (c) triglycerides, 1.69 versus 2.32 mmol/L, 17.2%, and 2.19 versus 2.32 mmol/L, 5.6%, respectively. No changes in the serum lipid levels in patients of the CG were found. In conclusion, fresh red grapefruit contains higher quantities of bioactive compounds and has significantly higher antioxidant potential than blond grapefruit. Diet supplemented with fresh red grapefruit positively influences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. The addition of fresh red grapefruit to generally accepted diets could be beneficial for hyperlipidemic, especially hypertriglyceridemic, patients suffering from coronary atherosclerosis.", "title": "Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans." }, { "docid": "MED-1930", "text": "BACKGROUND/OBJECTIVES: Shorter leukocyte telomere length (LTL) is associated with several chronic diseases, but only a few studies have assessed the association between dietary factors and LTL. Our objective was to study the association between fats, fruits, vegetables and LTL in a cross-sectional study design. We hypothesized that intakes of fruits and vegetables would be positively associated with LTL and that intakes of fats, and especially saturated fatty acids (SFAs), would be negatively associated with LTL. SUBJECTS/METHODS: LTL was measured by quantitative real-time polymerase chain reaction in 1942 men and women aged 57-70 years from the Helsinki Birth Cohort Study. We assessed the whole diet by a validated semiquantitative 128-item food-frequency questionnaire. RESULTS: In general, there were only a few significant results. However, total fat and SFA intake (P=0.04 and 0.01, respectively) were inversely associated with LTL in men adjusting for age and energy intake. In women, vegetable intake was positively associated with LTL (P=0.05). Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits (P=0.05). We found no association between LTL and body mass index, waist-hip ratio, smoking, physical activity or educational attainment. CONCLUSIONS: In this cross-sectional study of elderly men and women, there were only a few statistically significant effects of diet, but in general they support the hypothesis that fat and vegetable intakes were associated with LTL.", "title": "Leukocyte telomere length and its relation to food and nutrient intake in an elderly population." }, { "docid": "MED-1261", "text": "Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results.", "title": "‘Catalytic’ doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials" }, { "docid": "MED-1612", "text": "Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.", "title": "Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load." }, { "docid": "MED-2505", "text": "BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.", "title": "Ten years of life: Is it a matter of choice?" }, { "docid": "MED-2183", "text": "Objective Cooking programs are growing in popularity; however an extensive review has not examined overall impact. Therefore, this study reviewed previous research on cooking/home food preparation interventions and diet and health-related outcomes among adults and identified implications for practice and research. Design Literature review and descriptive summative method. Main outcome measures Dietary intake, knowledge/skills, cooking attitudes and self-efficacy/confidence, health outcomes. Analysis Articles evaluating effectiveness of interventions that included cooking/home food preparation as the primary aim (January 1980 through December 2011) were identified via OVID MEDLINE, Agricola and Web of Science databases. Studies grouped according to design and outcomes were reviewed for validity using an established coding system. Results were summarized for several outcome categories. Results Of 28 studies identified, 12 included a control group with six as non-randomized and six as randomized controlled trials. Evaluation was done post-intervention for five studies, pre- and post-intervention for 23 and beyond post-intervention for 15. Qualitative and quantitative measures suggested a positive influence on main outcomes. However, non-rigorous study designs, varying study populations, and use of non-validated assessment tools limited stronger conclusions. Conclusions and Implications Well-designed studies are needed that rigorously evaluate long-term impact on cooking behavior, dietary intake, obesity and other health outcomes.", "title": "Impact of cooking and home food preparation interventions among adults: outcomes and implications for future programs" }, { "docid": "MED-2899", "text": "The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.", "title": "Iris color and macular pigment optical density." }, { "docid": "MED-5073", "text": "Almond (Prunus dulcis[Mill.] D.A. Webb) skins have been proposed as a source of bioactive polyphenols. In this article, the phenolic composition and antioxidant activity of almond skins obtained from different processes (blanching [freeze-drying], blanching + drying, and roasting) were studied. A total of 31 phenolic compounds corresponding to flavan-3-ols (33% to 56% of the total of phenolic compounds identified), flavonol glycosides (9% to 36%), hydroxybenzoic acids and aldehydes (6% to 26%), flavonol aglycones (1.7% to 18%), flavanone glycosides (3% to 7.7%), flavanone aglycones (0.69% to 5.4%), hydroxycinnamic acids (0.65% to 2.6%), and dihydroflavonol aglycones (0% to 2.8%) were determined in the skins from 3 different varieties of almonds. The total contents of phenolic compounds identified were significantly (P < 0.05) higher (around 2-fold) in the roasted samples than in the blanched almonds (freeze-dried). Industrial drying (oven drying) of the blanched almond skins produced an increase (< 2-fold) in the contents of phenolic compounds, although the results were only statistically significant (P < 0.05) for some samples. The antioxidant activity (ORAC values) was higher for the roasted samples (0.803 to 1.08 mmol Trolox/g), followed by the samples subjected to blanching + drying (0.398 to 0.575 mmol Trolox/g) and then the blanched (freeze-dried) samples (0.331 to 0.451 mmol Trolox/g). Roasting is the most suitable type of industrial processing of almonds to obtain almond skin extracts with the greatest antioxidant capacity.", "title": "Polyphenols and antioxidant properties of almond skins: influence of industrial processing." }, { "docid": "MED-1968", "text": "Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.", "title": "Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects." }, { "docid": "MED-2593", "text": "Background Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person. Methods We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality. Results During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). Conclusions Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165. Trial registration Clinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.", "title": "Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial" }, { "docid": "MED-1936", "text": "BACKGROUND: The underlying molecular mechanisms of the vasculoprotective effects of physical exercise are incompletely understood. Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. This study examines the effects of exercising on vascular telomere biology and endothelial apoptosis in mice and the effects of long-term endurance training on telomere biology in humans. METHODS AND RESULTS: C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle-checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity. To test the significance of these data in humans, telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls. CONCLUSIONS: Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.", "title": "Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall." }, { "docid": "MED-5118", "text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.", "title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial." }, { "docid": "MED-1922", "text": "In the past decade, the growing field of telomere science has opened exciting new avenues for understanding the cellular and molecular substrates of stress and stress-related aging processes ver the lifespan. Shorter telomere length is associated with advancing chronological age and also increased disease morbidity and mortality. Emerging studies suggest that stress accelerates the erosion of telomeres from very early in life and possibly even influences the initial (newborn) setting of telomere length. In this review, we highlight recent empirical evidence linking stress and mental illnesses at various times across the lifespan with telomere erosion. We first present findings in the developmental programming of telomere biology linking prenatal stress to newborn and adult telomere length. We then present findings linking exposure to childhood trauma and to certain mental disorders with telomere shortening. Last, we review studies that characterize the relationship between related health-risk behaviors with telomere shortening over the lifespan, and how this process may further buffer the negative effects of stress on telomeres. A better understanding of the mechanisms that govern and regulate telomere biology throughout the lifespan may inform our understanding of etiology and the long-term consequences of stress and mental illnesses on aging processes in diverse populations and settings.", "title": "Stress and Telomere Biology: A Lifespan Perspective" }, { "docid": "MED-4084", "text": "Experiences with food intake, diet manipulations and fast were registered in rheumatic patients. The study was a questionnaire-based survey in which 742 patients participated. It comprised 290 patients with rheumatoid arthritis, 51 patients with juvenile rheumatoid arthritis, 87 patients with ankylosing spondylitis, 51 patients with psoriatic arthropathy, 65 patients with primary fibromyalgia and 34 patients with osteoarthritis. One third of the patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthropathy reported aggravation of disease symptoms after intake of certain foods while 43% of the patients with juvenile rheumatoid arthritis and 42% of the patients with primary fibromyalgia stated the same. Twenty-six percent of the patients with juvenile rheumatoid arthritis and 23% of the patients with rheumatoid arthritis, ankylosing spondylitis and primary fibromyalgia had previously tried certain diets in the attempt to alleviate disease symptoms, whereas 13% of the patients with psoriatic arthropathy and 10% with osteoarthritis had tried diet therapy. Less pain and stiffness were reported by 46% of the patients and 36% reported reduced joint swelling. Similar beneficial effects of diet were also reported in other rheumatic disease groups. Fifteen percent of the patients with rheumatoid arthritis and ankylosing spondylitis had been through a fasting period. Less pain and stiffness were reported by 2/3 of the patients in both groups and half of the patients in both groups reported a reduced number of swollen joints.", "title": "Diet and disease symptoms in rheumatic diseases--results of a questionnaire based survey." }, { "docid": "MED-2941", "text": "Several cohort studies have examined the association of carotid intima-media thickness (IMT) with the risk of stroke or myocardial infarction in apparently healthy persons. We investigated the predictive value of IMT of cardiovascular mortality in elderly community-dwelling people, beyond the prediction provided by age and MMSE. assessed by means of a multivariate Cox model. Carotid IMT and plaque were evaluated bilaterally with ultrasonography in 298 people older than 75 years ( 120 men and 178 women, average age: 79.6 years). The LILAC study started on July 25, 2000. Consultations were repeated every year. The follow-up ended on November 30, 2004. During the mean follow-up span of 1152 days, 30 subjects (21 men and nine women) died. Nine deaths were attributable to cardiovascular causes Imyocardial infarction: two men and three women; stroke: two men and two women). The age- and MMSE-adjusted relative risk (RR) and 95% confidence interval (95% CI) of developing all-cause mortality was assessed. A 0.3 mm increase in left IMT was associated with a RR of predicted 1.647 (1.075-2.524), and a similar increase in right IMT with a RR of 3.327 (1.429-7.746). For cardiovascular mortality, the corresponding RR values were 2.351 (1.029-5.372) and 2.890 (1.059-7.891), respectively. Carotid IMT assessed by ultrasonography is positively associated with an increased risk of all-cause and cardiovascular death in elderly community-dwelling people.", "title": "Common carotid intima-media thickness is predictive of all-cause and cardiovascular mortality in elderly community-dwelling people: Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study" }, { "docid": "MED-2519", "text": "To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.", "title": "Caloric restriction in humans: potential pitfalls and health concerns." }, { "docid": "MED-4850", "text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.", "title": "Antioxidants in vegan diet and rheumatic disorders." }, { "docid": "MED-3132", "text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.", "title": "Legume promotion in counselling: an e-mail survey of dietitians." }, { "docid": "MED-2851", "text": "OBJECTIVE Higher heme iron intake is associated with increased type 2 diabetes risk. However, no previous study has evaluated gestational diabetes mellitus (GDM) risk in relation to heme iron intake during pregnancy. We investigated associations of maternal preconceptional and early pregnancy heme and nonheme iron intake with subsequent GDM risk. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study of 3,158 pregnant women. A food frequency questionnaire was used to assess maternal diet. Multivariable generalized linear regression models were used to derive estimates of relative risks (RRs) and 95% CIs. RESULTS Approximately 5.0% of the cohort developed GDM (n = 158). Heme iron intake was positively and significantly associated with GDM risk (Ptrend = 0.04). After adjusting for confounders, women reporting the highest heme iron intake levels (≥1.52 vs. <0.48 mg per day) experienced a 3.31-fold–increased GDM risk (95% CI 1.02–10.72). In fully adjusted models, we noted that a 1-mg per day increase in heme iron was associated with a 51% increased GDM risk (RR 1.51 [95% CI 0.99–2.36]). Nonheme iron was inversely, though not statistically significantly, associated with GDM risk, and the corresponding RRs were 1.00, 0.83, 0.62, and 0.61 across quartiles of nonheme iron intake (Ptrend = 0.08). CONCLUSIONS High levels of dietary heme iron intake during the preconceptional and early pregnancy period may be associated with increased GDM risk. Associations of GDM risk with dietary nonheme iron intake are less clear. Confirmation of these findings by future studies is warranted.", "title": "Gestational Diabetes Mellitus in Relation to Maternal Dietary Heme Iron and Nonheme Iron Intake" }, { "docid": "MED-4031", "text": "INTRODUCTION: High low-density lipoproteins (LDL) cholesterol is one of the major risk factors for cardiovascular disease. In recent years, some evidence has been presented that periodontitis, an infectious inflammatory condition of the periodontium, is associated with an increased risk of cardiovascular disease. To further elucidate this association, we have studied the levels of LDL cholesterol, a known risk marker for cardiovascular disease, in a periodontally-diseased group. METHODS: The levels of serum LDL cholesterol in 47 subjects with mild to severe (clinical attachment loss equal to or greater than 1 mm) chronic generalized (at least 30% of teeth affected) periodontitis with the mean age of 42.21 ± 1.46 years were measured and compared with those obtained from 42 age (39.83 ± 0.94) and sex matched controls. Both groups were free from systemic illnesses. RESULTS: The mean serum LDL cholesterol in periodontitis patients was found to be significantly higher (P < 0.001) as compared to that of the controls. The mean clinical attachment loss was positively correlated with serum LDL cholesterol (P < 0.01) and gingival index (P<0.05). The frequency of persons with pathologic values of LDL cholesterol was significantly higher in periodontitis patients compared with that of the controls. CONCLUSIONS: These results showed that high serum LDL cholesterol may be associated with periodontitis in healthy people. However, it is unclear whether periodontitis causes an increase in the levels of serum LDL or an increased LDL is a risk factor for both periodontitis and cardiovascular disease.", "title": "Association of serum LDL cholesterol level with periodontitis among patients visiting a tertiary-care hospital." }, { "docid": "MED-4023", "text": "INTRODUCTION: The aim of the study was to determine the potential relation between vegetarian diet and tooth erosion and abrasion. MATERIAL/METHODS: The examination included 46 vegetarians and the same number in the control group. Clinical research was carried out in order to detect the presence of abrasive and erosive changes and the level of hygiene in oral cavities. The questionnaire survey concerned dietary and hygienic habits. Statistical analysis of the data was conducted with Chi-square test and Mann-Whitney U test. The relations between following a vegetarian diet and the occurrence of non-carious cavities was tested with models of logistic regression. RESULTS: Tooth erosion was present among 39.1% of vegetarians and 23.9% of controls, while abrasion appeared among 26.1% and 10.9%, respectively, and the differences were statistically insignificant. The distribution of the changes was similar in both groups. Among vegetarians, significantly more frequent consumption of sour products (predominantly raw vegetables and fruit and tomatoes) was observed. The level of oral hygiene and hygienic habits were similar in both groups. The analysis of statistical regression did not reveal any relations between following a vegetarian diet and the occurrence of tooth erosion and abrasion. DISCUSSION: The results did not reveal any direct influence of vegetarian diet on the occurrence of erosive and abrasive changes. However, in the vegetarian group, more frequent consumption of some sour products and more commonly used horizontal brushing method were observed, with a slightly higher occurrence of non-carious cavities. Further research is required to obtain unambiguous conclusions.", "title": "Assessment of the influence of vegetarian diet on the occurrence of erosive and abrasive cavities in hard tooth tissues." }, { "docid": "MED-5016", "text": "OBJECTIVE: The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. DESIGN: The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. SUBJECTS: Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. INTERVENTIONS: Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. RESULTS: Plasma lathosterol concentration (P < 0.001), the ratio plasma lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (P<0.001) and apoB (P<0.001) levels were significantly different among the diets and were significantly lower during coconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (P< or =0.001) different among the diets and were not significantly different between buffer and coconut diets. CONCLUSIONS: These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.", "title": "Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels." }, { "docid": "MED-2942", "text": "BACKGROUND: There are no long-term prospective studies assessing the impact of the vegan diet on vitamin B-12 (B-12) status. Many vegans take B-12 supplements irregularly or refuse to adopt them at all, considering them to be \"unnatural\" products. The use of B-12 fortified food may be an alternative. Therefore, we aimed to estimate the long-term effect of a vegan diet on serum B-12 concentrations in healthy omnivore adults, comparing the influence of natural products consumption and B-12 fortified food. MATERIAL AND METHODS: A five year prospective study was carried out comprising 20 omnivore healthy adult subjects, who moved to strict vegan diet for 5 years. Ten volunteers followed vegan diet based entirely on natural products, while the remaining ten subjects consumed food fortified in B-12. In all subjects serum vitamin B-12 concentration was determined before and 6, 12, 24 and 60 months after the implementation of the diet. RESULTS: A significant decrease (p < 0.0002) of serum B-12 concentrations in the whole studied group was noted after 60 months of vegan diet. However, observed changes were in fact limited to the subgroup consuming exclusively natural products (p < 0.0001). CONCLUSIONS: Transition from omnivore to vegan diet is associated with the risk of vitamin B-12 deficiency. B-12 fortified products might constitute a valuable alternative in vegans refusing to take vitamin supplements.", "title": "The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study." }, { "docid": "MED-2529", "text": "We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation. Copyright 2001 by W.B. Saunders Company", "title": "Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function." }, { "docid": "MED-2237", "text": "In India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non-Indian alcohol beverages on lung carcinogenesis. We conducted a case-control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally-weighted running-line smoothers (loess) to find the most plausible curve for the dose-response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette-equivalent pack-years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96-6.95) and 6.45 (95%CI=4.38-9.50) for more than 30 years of cigarette-only and bidi-only smoking, respectively, and 6.87 (95%CI=4.62-10.2) and 10.7 (95%CI=5.82-19.6) for more than 12 weighted cumulative cigarette-only and bidi-only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never-smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02-7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered. Copyright 2003 Wiley-Liss, Inc.", "title": "Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India." }, { "docid": "MED-4827", "text": "Background Several prospective studies suggest that use of cholesterol-lowering statin drugs is inversely associated with advanced stage and possibly high-grade prostate cancer. One study reported that men with low cholesterol had a lower risk of high-grade prostate cancer. Given these findings, we investigated the association between low serum cholesterol and prostate cancer risk in the Prostate Cancer Prevention Trial (PCPT). Methods We conducted a cohort study of 5,586 men aged ≥ 55 years old who were randomized to the placebo arm of the PCPT between 1993 and 1996. Serum cholesterol was measured enzymatically at entry. By the end of follow-up, 1,251 prostate cancer cases were confirmed. We used logistic regression to calculate the multivariable odds ratio (OR) of total, and Gleason 2-6 (n=993), 7 (n=199), and 8-10 (n=59) prostate cancer comparing low (normal: < 200 mg/dL) to high (borderline and elevated cholesterol: ≥ 200 mg/dL) serum cholesterol. Results Men with low cholesterol had a lower risk of Gleason 8-10 prostate cancer (OR=0.41, 95% confidence interval (CI) 0.22-0.77) than men with high cholesterol. No association was present for prostate cancer overall (OR=0.97, 95% CI 0.85-1.11), Gleason 2-6 disease (OR=1.03, 95% CI 0.89-1.18), or Gleason 7 disease (OR=0.93, 95% CI 0.69-1.24). Conclusion These prospective results support that men with low cholesterol have a reduced risk of high-grade prostate cancer. These and other contemporary data suggest that cholesterol metabolism should be investigated further in the etiology of prostate cancer.", "title": "Men with Low Serum Cholesterol Have a Lower Risk of High-Grade Prostate Cancer in the Placebo Arm of the Prostate Cancer Prevention Trial" }, { "docid": "MED-2945", "text": "BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.", "title": "Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men." }, { "docid": "MED-2853", "text": "Background Two criteria based on a 2 h 75 g OGTT are being used for the diagnosis of gestational diabetes (GDM), those recommended over the years by the World Health Organization (WHO), and those recently recommended by the International Association for Diabetes in Pregnancy Study Group (IADPSG), the latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to systematically review the evidence for the associations between GDM (according to these criteria) and adverse outcomes. Methods We searched relevant studies in MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR, EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and perinatal outcomes in untreated women. Only studies with universal application of a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence intervals (CI) were obtained for each study. We combined study results using a random-effects model. Inconsistency across studies was defined by an inconsistency index (I2) > 50%. Results Data were extracted from eight studies, totaling 44,829 women. Greater risk of adverse outcomes was observed for both diagnostic criteria. When using the WHO criteria, consistent associations were seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data were available for the IADPSG criteria, and associations were inconsistent across studies (I2 ≥ 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p = 0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding either the HAPO or the EBDG studies minimally altered these associations, but the RRs seen for the IADPSG criteria were reduced after excluding HAPO. Conclusions The WHO and the IADPSG criteria for GDM identified women at a small increased risk for adverse pregnancy outcomes. Associations were of similar magnitude for both criteria. However, high inconsistency was seen for those with the IADPSG criteria. Full evaluation of the latter in settings other than HAPO requires additional studies.", "title": "Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria" }, { "docid": "MED-2947", "text": "PURPOSE: To measure prospectively and directly both organ dose and effective dose (ED) for adult cardiac and pulmonary computed tomographic (CT) angiography by using current clinical protocols for 64-detector CT in an anthropomorphic female phantom and to estimate lifetime attributable risk of breast and lung cancer incidence on the basis of measured ED and organ dose. MATERIALS AND METHODS: Cardiac and pulmonary 64-detector CT angiography was performed by using current clinical protocols to evaluate the pulmonary veins (electrocardiographically [ECG] gated, 64 sections at 0.625-mm collimation, 120 kVp, 300 mA, 0.35-second tube rotation), native coronary arteries (ECG gated; 64 sections at 0.625 mm; 120 kVp; maximum current, 500-750 mA; minimum, 100-350 mA; 0.35-second tube rotation) and pulmonary embolus (64 sections at 1.25 mm, 140 kVp, 645 mA, 0.5-second tube rotation). Absorbed organ doses were measured by using an anthropomorphic female phantom and metal oxide semiconductor field effect transistor detectors. ED was calculated from measured organ doses and the dose-length product. RESULTS: ED for current adult cardiac and pulmonary 64-detector CT angiography protocols were 12.4-31.8 mSv. Overall, skin, breast, and esophagus and heart had the highest recorded absorbed organ doses. Relative risk for breast cancer incidence for girls and women was 1.004-1.042 for a single examination. Relative risk for lung cancer incidence for men and women was 1.005-1.076 from a single examination. CONCLUSION: EDs and organ doses from 64-detector CT are higher than those previously reported for adult cardiac and pulmonary CT angiography protocols. Risk for breast and lung cancer induction from these studies is greatest for the younger patient population. (c) RSNA, 2007.", "title": "Radiation dose from contemporary cardiothoracic multidetector CT protocols with an anthropomorphic female phantom: implications for cancer induction." }, { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-3395", "text": "The available large prospective studies supporting an inverse association between better adherence to the Mediterranean diet and lower mortality have mainly included older adults. It is not clear whether this inverse association is also present among younger individuals at lower mortality risk. Our aim was to assess the association between adherence to the Mediterranean diet and total mortality in middle-aged adults from the Seguimiento Universidad de Navarra (SUN) Project. We followed 15,535 Spanish university graduates for a mean of 6.8 y. Their mean age was 38 ± 12 y, 59.6% were females, and all were initially free of cardiovascular disease, cancer, and diabetes. A validated FFQ was used to assess dietary habits. Adherence to the Mediterranean diet was categorized into 3 groups according to the Mediterranean Diet Score (low, 0-2 points; moderate, 3-5 points; and high, 6-9 points). The outcome variable was total mortality. Cox proportional hazards models were used to estimate HR and 95% CI. We adjusted the estimates for sex, age, years of university education, BMI, smoking, physical activity, television watching, history of depression and baseline hypertension, and hypercholesterolemia. We observed 125 deaths during 105,980 person-years of follow-up. The fully adjusted HR for moderate and high adherence were 0.58 (95% CI: 0.34, 0.99; P = 0.05) and 0.38 (95% CI: 0.21, 0.70; P = 0.002), respectively. For each 2-point increment in the Mediterranean Diet Score, the HR of death was 0.72 (95% CI: 0.58, 0.91; P = 0.006). Among highly educated, middle-aged adults, adherence to the traditional Mediterranean diet was associated with reduced risk of death.", "title": "The Mediterranean diet is associated with a reduction in premature mortality among middle-aged adults." }, { "docid": "MED-3140", "text": "To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.", "title": "Legumes: the most important dietary predictor of survival in older people of different ethnicities." }, { "docid": "MED-4544", "text": "Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.", "title": "Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer." }, { "docid": "MED-2371", "text": "Background Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk. Objective To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults. Methods Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel. Results Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%; p = 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%; p < 0.01) and lowered serum total cholesterol (-18 ± 18 vs. -5 ± 21 mg/dL; p < 0.01) and LDL (-14 ± 20 vs. -2 ± 19 mg/dL; p = 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline. Conclusions Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.", "title": "Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk" }, { "docid": "MED-4540", "text": "BACKGROUND: Red yeast rice (RYR) is a widely available dietary supplement used by millions of patients as an alternative therapy for hyperlipidemia. It contains 14 active compounds called monacolins that inhibit hepatic cholesterol synthesis. Although studies have suggested that some formulations of RYR may be effective and safe for lipid lowering, monacolin levels are not standardized among marketed products and are generally not published on labels. We evaluated monacolin levels in 12 commercial RYR formulations and tested for citrinin, a mycotoxin that is nephrotoxic in animals. METHODS: Each formulation of RYR was labeled \"600 mg/capsule\" of active product. Analyses for monacolins and citrinin were performed between August 2006 and June 2008 using high-performance liquid chromatography with mass spectroscopy-mass spectroscopy detection. Laboratory analyses of RYR products were conducted by ConsumerLab.com, White Plains, New York. RESULTS: There was marked variability in the 12 RYR products in total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule). Four products had elevated levels of citrinin. CONCLUSIONS: We found striking variability in monacolin content in 12 proprietary RYR products and the presence of citrinin in one-third of the formulations tested. Although RYR may have potential as an alternative lipid-lowering agent, our findings suggest the need for improved standardization of RYR products and product labeling. Until this occurs, physicians should be cautious in recommending RYR to their patients for the treatment of hyperlipidemia and primary and secondary prevention of cardiovascular disease.", "title": "Marked variability of monacolin levels in commercial red yeast rice products: buyer beware!" }, { "docid": "MED-2892", "text": "PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.", "title": "The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity." }, { "docid": "MED-2374", "text": "OBJECTIVES: To assess the dose-response relationship between egg consumption and the risk of cardiovascular diseases (CVD) and diabetes. METHODS: We systematically searched MEDLINE database through December 2012. Fixed- or random-effects model was used to pool the relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses was performed to explore the potential sources of heterogeneity. Weighted linear regression model was used to estimate the dose-response relationship. RESULTS: Fourteen studies involving 320,778 subjects were included. The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02-1.38), 1.83 (95% CI 1.42-2.37), 1.68 (95% CI 1.41-2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03-1.10), 1.40 (95% CI 1.25-1.57), 1.29 (95% CI 1.21-1.37), respectively. Subgroup analyses showed that population in other western countries have increased CVD than ones in USA (RR 2.00, 95% CI 1.14 to 3.51 vs 1.13, 95% CI 0.98 to 1.30, P = 0.02 for subgroup difference). CONCLUSIONS: Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis." }, { "docid": "MED-4001", "text": "Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans.", "title": "An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity" }, { "docid": "MED-2382", "text": "BACKGROUND: Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal allergic reactions in the United States, and the prevalence appears to be increasing. OBJECTIVES: We sought to determine the US prevalence of self-reported peanut, TN, and sesame allergy in 2008 and compare results with comparable surveys conducted in 1997 and 2002. METHODS: A nationwide, cross-sectional, random telephone survey for peanut and TN allergy was conducted with a previously used questionnaire, with additional questions about sesame. RESULTS: A total of 5,300 households (13,534 subjects) were surveyed (participation rate, 42% vs 52% in 2002 and 67% in 1997). Peanut allergy, TN allergy, or both was reported by 1.4% of subjects (95% CI, 1.2% to 1.6%) compared with 1.2% in 2002 and 1.4% in 1997. For adults, the prevalence was 1.3% (95% CI, 1.1% to 1.6%), which was not significantly different from prior surveys. However, the prevalence of peanut or TN allergy for children younger than 18 years was 2.1% (95% CI, 1.6% to 2.7%) compared with 1.2% in 2002 (P = .007) and 0.6% in 1997 (P < .001). The prevalence of peanut allergy in children in 2008 was 1.4% (95% CI, 1.0% to 1.9%) compared with 0.8% in 2002 (P = not significant) and 0.4% in 1997 (P < .0001). The prevalence of childhood TN allergy increased significantly across the survey waves (1.1% in 2008, 0.5% in 2002, and 0.2% in 1997). Sesame allergy was reported by 0.1% (95% CI, 0.0% to 0.2%). CONCLUSIONS: Although caution is required in comparing surveys, peanut allergy, TN allergy, or both continue to be reported by more than 1% of the US population (eg, >3 million subjects) and appear to be increasingly reported among children over the past decade. Sesame allergy is reported much less commonly. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.", "title": "US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up." }, { "docid": "MED-3248", "text": "OBJECTIVE: To examine the relation between retinal artery disease and cerebral small-vessel disease (SVD). METHODS: In a prospective cohort of patients with symptomatic atherosclerotic disease, the authors performed retinal photographs and brain MRI. Two ophthalmologists, not aware of the MR results, independently assessed retinal arterial narrowing, crossings, sclerosis, and tortuosity according to standard scoring lists. Two observers independently assessed white matter lesions (WML) and lacunar infarcts on the MR images. Lesions were considered abnormal only when both ophthalmologists or MR raters agreed. Cerebral SVD was defined as the presence of WML or lacunar infarcts. RESULTS: In 179 patients, retinal photographs and brain MRI were performed. Of the 108 patients with MR signs of SVD, 92% had at least one retinal vascular abnormality; of the 71 patients without SVD, 77% had retinal pathology (p < 0.01). All types of retinal vascular pathology occurred more frequently in patients with SVD, but only retinal arterial narrowing and sclerosis differed significantly. In the 109 normotensive patients, the presence of any retinal vascular change correlated with signs of SVD (p = 0.01). CONCLUSION: Pathologic changes in the retinal arteries parallel changes in the small cerebral arteries that cause WML and lacunes, both in hypertensive and in normotensive patients.", "title": "Retinal arterial changes correlate with cerebral small-vessel disease." }, { "docid": "MED-1257", "text": "Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.", "title": "Protein and coronary heart disease: the role of different protein sources." }, { "docid": "MED-1917", "text": "The telomere length is an indicator of biologic aging, and shorter telomeres have been associated with coronary artery calcium (CAC), a validated indicator of coronary atherosclerosis. It is unclear, however, whether healthy lifestyle behaviors affect the relation between telomere length and CAC. In a sample of subjects aged 40 to 64 years with no previous diagnosis of coronary heart disease, stroke, diabetes mellitus, or cancer (n = 318), healthy lifestyle behaviors of greater fruit and vegetable consumption, lower meat consumption, exercise, being at a healthy weight, and the presence of social support were examined to determine whether they attenuated the association between a shorter telomere length and the presence of CAC. Logistic regression analyses controlling for age, gender, race/ethnicity, and Framingham risk score revealed that the relation between having shorter telomeres and the presence of CAC was attenuated in the presence of high social support, low meat consumption, and high fruit and vegetable consumption. Those with shorter telomeres and these characteristics were not significantly different from those with longer telomeres. Conversely, the subjects with shorter telomeres and less healthy lifestyles had a significantly increased risk of the presence of CAC: low fruit and vegetable consumption (odds ratio 3.30, 95% confidence interval 1.61 to 6.75), high meat consumption (odds ratio 3.33, 95% confidence interval 1.54 to 7.20), and low social support (odds ratio 2.58, 95% confidence interval 1.24 to 5.37). Stratification by gender yielded similar results for men; however, among women, only fruit and vegetable consumption attenuated the shorter telomere length and CAC relation. In conclusion, the results of the present study suggest that being involved in healthy lifestyle behaviors might attenuate the association between shorter telomere length and coronary atherosclerosis, as identified using CAC. 2010 Elsevier Inc. All rights reserved.", "title": "Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium." }, { "docid": "MED-3394", "text": "Few studies have examined multiple risk factors for mortality or formally compared their associations across specific causes of death. The authors used competing risks survival analysis to evaluate associations of lifestyle and dietary factors with all-cause and cause-specific mortality among 50,112 participants in the Nurses’ Health Study. There were 4,893 deaths between 1986 and 2004: 1,026 from cardiovascular disease, 931 from smoking-related cancers, 1,430 from cancers not related to smoking, and 1,506 from all other causes. Age, body mass index at age 18 years, weight change, height, current smoking and pack-years of smoking, glycemic load, cholesterol intake, systolic blood pressure and use of blood pressure medications, diabetes, parental myocardial infarction before age 60 years, and time since menopause were directly related to all-cause mortality, whereas there were inverse associations for physical activity and intakes of nuts, polyunsaturated fat, and cereal fiber. Moderate alcohol consumption was associated with decreased mortality. A model that incorporated differences in the associations of some risk factors with specific causes of death had a significantly better fit compared with a model in which all risk factors had common associations across all causes. In the future, this new model may be used to identify individuals at increased risk of mortality.", "title": "Risk Factors for Mortality in the Nurses’ Health Study: A Competing Risks Analysis" }, { "docid": "MED-4088", "text": "The influence of a 3-week vegetarian diet and fasting on serum concentration of peroxides, lipids, apolipoproteins, and plasma fibrinogen was studied in ten middle-aged fibromyalgia/fibrositis patients (eight women, two men). Mean serum peroxide concentration (estimated as thiobarbituric acid reacting substances) was reduced from 3.60 +/- 0.14 to 2.82 +/- 0.15 umol/l (p = 0.01) and plasma fibrinogen from 3.33 +/- 0.25 to 2.74 +/- 0.15 g/l (p = 0.02). Serum total cholesterol fell from 6.61 +/- 0.50 to 4.83 +/- 0.35 mmol/l (p < 0.0001), apolipoprotein B from 1.77 +/- 0.14 to 1.31 +/- 0.11 g/l (p < 0.0001), and apolipoprotein A from 1.41 +/- 0.09 to 1.23 +/- 0.05 g/l (p = 0.03). High density lipoprotein cholesterol concentration also decreased somewhat (from 1.26 +/- 0.09 to 1.07 +/- 0.04 mmol/l, p = 0.03) An atherogenic index, reflecting the balance between low and high density lipoproteins, was reduced by 31% (from 5.74 +/- 0.79 to 3.97 +/- 0.60, p = 0.02). The results suggest that vegetarian diet/fasting may have a beneficial influence on the concentration of serum peroxides and plasma fibrinogen concentration, and on the serum level of several lipoprotein-related coronary risk factors.", "title": "Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet." }, { "docid": "MED-2444", "text": "This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to-moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential.", "title": "Side-effect profile of cyclosporin A in patients treated for psoriasis." }, { "docid": "MED-1888", "text": "BACKGROUND Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans. METHODS We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography. RESULTS Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001). An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors (P<0.001), as well as in lower-risk subgroups. CONCLUSIONS The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events. (Funded by the National Institutes of Health and others.)", "title": "Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk" }, { "docid": "MED-3782", "text": "Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men.", "title": "Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival" }, { "docid": "MED-1918", "text": "BACKGROUND: Telomerase activity is a predictor of long-term cellular viability, which decreases with chronic psychological distress (Epel et al., 2004). Buddhist traditions claim that meditation decreases psychological distress and promotes well-being (e.g., Dalai Lama and Cutler, 2009). Therefore, we investigated the effects of a 3-month meditation retreat on telomerase activity and two major contributors to the experience of stress: Perceived Control (associated with decreased stress) and Neuroticism (associated with increased subjective distress). We used mediation models to test whether changes in Perceived Control and Neuroticism explained meditation retreat effects on telomerase activity. In addition, we investigated whether two qualities developed by meditative practice, increased Mindfulness and Purpose in Life, accounted for retreat-related changes in the two stress-related variables and in telomerase activity. METHODS: Retreat participants (n=30) meditated for ∼6 h daily for 3 months and were compared with a wait-list control group (n=30) matched for age, sex, body mass index, and prior meditation experience. Retreat participants received instruction in concentrative meditation techniques and complementary practices used to cultivate benevolent states of mind (Wallace, 2006). Psychological measures were assessed pre- and post-retreat. Peripheral blood mononuclear cell samples were collected post-retreat for telomerase activity. Because there were clear, a priori hypotheses, 1-tailed significance criteria were used throughout. RESULTS: Telomerase activity was significantly greater in retreat participants than in controls at the end of the retreat (p<0.05). Increases in Perceived Control, decreases in Neuroticism, and increases in both Mindfulness and Purpose in Life were greater in the retreat group (p<0.01). Mediation analyses indicated that the effect of the retreat on telomerase was mediated by increased Perceived Control and decreased Neuroticism. In turn, changes in Perceived Control and Neuroticism were both partially mediated by increased Mindfulness and Purpose in Life. Additionally, increases in Purpose in Life directly mediated the telomerase group difference, whereas increases in Mindfulness did not. CONCLUSIONS: This is the first study to link meditation and positive psychological change with telomerase activity. Although we did not measure baseline telomerase activity, the data suggest that increases in perceived control and decreases in negative affectivity contributed to an increase in telomerase activity, with implications for telomere length and immune cell longevity. Further, Purpose in Life is influenced by meditative practice and directly affects both perceived control and negative emotionality, affecting telomerase activity directly as well as indirectly. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Intensive meditation training, immune cell telomerase activity, and psychological mediators." }, { "docid": "MED-4560", "text": "The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.", "title": "Preventing and arresting coronary atherosclerosis." }, { "docid": "MED-1886", "text": "Background Nuclear magnetic resonance (NMR) spectroscopy measures the number and size of lipoprotein particles, instead of their cholesterol or triglyceride content, but its clinical utility is uncertain. Methods and Results Baseline lipoproteins were measured by NMR in 27,673 initially healthy women followed for incident cardiovascular disease (CVD, N=1,015) over 11 years. Adjusting for non-lipid risk factors, hazard ratios (HRs) and 95% confidence intervals (CIs) for top vs bottom quintile of NMR-measured lipoprotein particle concentration (particles/L) were, for low-density lipoprotein (LDLNMR) 2.51 (1.91−3.30), high-density lipoprotein (HDLNMR) 0.91 (0.75−1.12), very-low-density lipoprotein (VLDLNMR) 1.71 (1.38−2.12), and LDLNMR/HDLNMR ratio 2.25 (1.80−2.81). Similarly-adjusted results for NMR-measured lipoprotein particle size (nanometers) were, for LDLNMR size 0.64 (0.52−0.79), HDLNMR size 0.65 (0.51−0.81), and VLDLNMR size 1.37 (1.10−1.70). Hazard ratios for NMR measures were comparable but not superior to standard lipids: total cholesterol 2.08 (1.63−2.67), LDL cholesterol 1.74 (1.40−2.16), HDL cholesterol 0.52 (0.42−0.64), triglycerides 2.58 (1.95−3.41), non-HDL cholesterol 2.52 (1.95−3.25), total/HDL cholesterol ratio 2.82 (2.23−3.58); and apolipoproteins: B100 2.57 (1.98−3.33), A-1 0.63 (0.52−0.77), B100/A-1 ratio 2.79 (2.21−3.54). There was essentially no reclassification improvement with adding LDLNMR particle concentration or apolipoprotein B100 to a model that already included the total/HDL cholesterol ratio and non-lipid risk factors (net reclassification index [NRI], 0% and 1.9%, respectively), nor did the addition of either variable result in a statistically significant improvement in the c-index. Conclusions In this prospective study of healthy women, CVD risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to standard lipids or apolipoproteins.", "title": "Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared with Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women" }, { "docid": "MED-2882", "text": "Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.", "title": "Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells." }, { "docid": "MED-2080", "text": "Beyond obvious functions in haemostasis and thrombosis, platelets are considered to be essential in proinflammatory surroundings such as atherosclerosis, allergy, rheumatoid arthritis and even cancer. In atherosclerosis, platelets facilitate the recruitment of inflammatory cells towards the lesion sites and release a plethora of inflammatory mediators, thereby enriching and boosting the inflammatory milieu. Platelets do so by interacting with endothelial cells, circulating leukocytes (monocytes, neutrophils, dendritic cells, T-cells) and progenitor cells. This cross-talk enforces leukocyte activation, adhesion and transmigration. Furthermore, platelets are known to function in innate host defense through the release of antimicrobial peptides and the expression of pattern recognition receptors. In severe sepsis, platelets are able to trigger the formation of neutrophil extracellular traps (NETs), which bind and clear pathogens. The present antiplatelet therapies that target key pathways of platelet activation and aggregation therefore hold the potential to modulate platelet-derived immune functions by reducing cellular interactions of platelets with other immune components and by reducing the secretion of inflammatory proteins into the milieu. The objective of this review is to update and discuss the current perceptions of the platelet immune constituents and their prospect as therapeutic targets in an atherosclerotic setting.", "title": "Platelets in atherosclerosis." }, { "docid": "MED-2498", "text": "Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.", "title": "Dietary Restriction, Growth Factors and Aging: from yeast to humans" }, { "docid": "MED-5239", "text": "Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.", "title": "Leucine signaling in the pathogenesis of type 2 diabetes and obesity" }, { "docid": "MED-2890", "text": "Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.", "title": "Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?" }, { "docid": "MED-2844", "text": "OBJECTIVE It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic β-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM. RESEARCH DESIGN AND METHODS A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors. RESULTS Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87–1.43), 1.31 (1.03–1.68), 1.51 (1.17–1.93), and 1.58 (1.21–2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10–1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk. CONCLUSIONS These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.", "title": "A Prospective Study of Prepregnancy Dietary Iron Intake and Risk for Gestational Diabetes Mellitus" }, { "docid": "MED-4877", "text": "BACKGROUND: Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS: PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION: Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.", "title": "Increased telomerase activity and comprehensive lifestyle changes: a pilot study." }, { "docid": "MED-4006", "text": "BACKGROUND: Dietary fat type is known to modulate the plasma lipid profile, but its effects on plasma homocysteine and inflammatory markers are unclear. OBJECTIVE: We investigated the effects of high-protein Malaysian diets prepared with palm olein, coconut oil (CO), or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease (CVD) in healthy adults. DESIGN: A randomized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects. The 3 test fats, namely palmitic acid (16:0)-rich palm olein (PO), lauric and myristic acid (12:0 + 14:0)-rich CO, and oleic acid (18:1)-rich virgin olive oil (OO), were incorporated at two-thirds of 30% fat calories into high-protein Malaysian diets. RESULTS: No significant differences were observed in the effects of the 3 diets on plasma total homocysteine (tHcy) and the inflammatory markers TNF-α, IL-1β, IL-6, and IL-8, high-sensitivity C-reactive protein, and interferon-γ. Diets prepared with PO and OO had comparable nonhypercholesterolemic effects; the postprandial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower (P < 0.05) than for the CO diet. Unlike the PO and OO diets, the CO diet was shown to decrease postprandial lipoprotein(a). CONCLUSION: Diets that were rich in saturated fatty acids prepared with either PO or CO, and an OO diet that was high in oleic acid, did not alter postprandial or fasting plasma concentrations of tHcy and selected inflammatory markers. This trial was registered at clinicaltrials.gov as NCT00941837.", "title": "Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homoc..." }, { "docid": "MED-2946", "text": "OBJECTIVE: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians. DESIGN: Double-blind, placebo controlled, randomised crossover study. SETTING: Community dwelling vegetarians. PARTICIPANTS: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. INTERVENTION: Vitamin B-12 (500 µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41). MEASUREMENT: Flow-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound. RESULTS: The mean age of the subjects was 45±9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150 pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09 mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09 mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028). CONCLUSIONS: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.", "title": "Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status." }, { "docid": "MED-1919", "text": "Telomerases constitute a group of specialized ribonucleoprotein enzymes that remediate chromosomal shrinkage resulting from the “end-replication” problem. Defects in telomere length regulation are associated with several diseases as well as with aging and cancer. Despite significant progress in understanding the roles of telomerase, the complete structure of the human telomerase enzyme bound to telomeric DNA remains elusive, with the detailed molecular mechanism of telomere elongation still unknown. By application of computational methods for distant homology detection, comparative modeling, and molecular docking, guided by available experimental data, we have generated a three-dimensional structural model of a partial telomerase elongation complex composed of three essential protein domains bound to a single-stranded telomeric DNA sequence in the form of a heteroduplex with the template region of the human RNA subunit, TER. This model provides a structural mechanism for the processivity of telomerase and offers new insights into elongation. We conclude that the RNA∶DNA heteroduplex is constrained by the telomerase TEN domain through repeated extension cycles and that the TEN domain controls the process by moving the template ahead one base at a time by translation and rotation of the double helix. The RNA region directly following the template can bind complementarily to the newly synthesized telomeric DNA, while the template itself is reused in the telomerase active site during the next reaction cycle. This first structural model of the human telomerase enzyme provides many details of the molecular mechanism of telomerase and immediately provides an important target for rational drug design.", "title": "Human telomerase model shows the role of the TEN domain in advancing the double helix for the next polymerization step" }, { "docid": "MED-2376", "text": "Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment. Copyright © 2014 Elsevier Inc. All rights reserved.", "title": "Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease." }, { "docid": "MED-2085", "text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.", "title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables." }, { "docid": "MED-2895", "text": "PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight \"retinal responders\" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two \"retinal nonresponders\" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one \"serum and retinal nonresponder\" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.", "title": "Dietary modification of human macular pigment density." }, { "docid": "MED-1926", "text": "OBJECTIVE: It has been reported that women benefit from the maintenance of telomere length by estrogen. Exercise may favorably influence telomere length, although results are inconsistent regarding the duration and type of exercise and the cell type used to measure telomere length. The purpose of this study was to investigate the relationship between habitual physical exercise and telomere length in peripheral blood mononuclear cells (PBMCs) in postmenopausal women. Postmenopausal women were chosen as study participants because they are typically estrogen deficient. METHODS: This experimental-control, cross-sectional study included 44 healthy, nondiabetic, nonsmoking, postmenopausal women. Habitual exercisers and sedentary participants were matched for age and body mass index. Body weight, height, blood pressure, and waist and hip circumference were measured. Mitochondrial DNA copy number and telomere length in PBMCs were determined, and biochemical tests were performed. Habitual physical exercise was defined as combined aerobic and resistance exercise performed for at least 60 minutes per session more than three times a week for more than 12 months. RESULTS: The mean age of all participants was 58.11 ± 6.84 years, and participants in the habitual exercise group had been exercising more than three times per week for an average of 19.23 ± 5.15 months. Serum triglyceride levels (P = 0.01), fasting insulin concentrations (P < 0.01), and homeostasis model assessment of insulin resistance (P < 0.01) were significantly lower and high-density lipoprotein cholesterol levels (P < 0.01), circulating adiponectin (P < 0.01), mitochondrial DNA copy number (P < 0.01), and telomere length (P < 0.01) were significantly higher in the habitual exercise group than in the sedentary group. In a stepwise multiple regression analysis, habitual exercise (β = 0.522, P < 0.01) and adiponectin levels (β = 0.139, P = 0.03) were the independent factors associated with the telomere length of PBMCs in postmenopausal women. CONCLUSIONS: Habitual physical exercise is associated with greater telomere length in postmenopausal women. This finding suggests that habitual physical exercise in postmenopausal women may reduce telomere attrition.", "title": "Habitual physical exercise has beneficial effects on telomere length in postmenopausal women." }, { "docid": "MED-1676", "text": "Starch in white wheat bread (WB) induces high postprandial glucose and insulin responses. For rye bread (RB), the glucose response is similar, whereas the insulin response is lower. In vitro studies suggest that polyphenol-rich berries may reduce digestion and absorption of starch and thereby suppress postprandial glycemia, but the evidence in humans is limited. We investigated the effects of berries consumed with WB or RB on postprandial glucose and insulin responses. Healthy females (n = 13-20) participated in 3 randomized, controlled, crossover, 2-h meal studies. They consumed WB or RB, both equal to 50 g available starch, with 150 g whole-berry purée or the same amount of bread without berries as reference. In study 1, WB was served with strawberries, bilberries, or lingonberries and in study 2 with raspberries, cloudberries, or chokeberries. In study 3, WB or RB was served with a mixture of berries consisting of equal amounts of strawberries, bilberries, cranberries, and blackcurrants. Strawberries, bilberries, lingonberries, and chokeberries consumed with WB and the berry mixture consumed with WB or RB significantly reduced the postprandial insulin response. Only strawberries (36%) and the berry mixture (with WB, 38%; with RB, 19%) significantly improved the glycemic profile of the breads. These results suggest than when WB is consumed with berries, less insulin is needed for maintenance of normal or slightly improved postprandial glucose metabolism. The lower insulin response to RB compared with WB can also be further reduced by berries.", "title": "Berries reduce postprandial insulin responses to wheat and rye breads in healthy women." }, { "docid": "MED-4007", "text": "Background Alzheimer's disease (AD) is characterized by early and region-specific declines in cerebral glucose metabolism. Ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain. An oral ketogenic compound, AC-1202, was tested in subjects with probable AD to examine if ketosis could improve cognitive performance. Methods Daily administration of AC-1202 was evaluated in 152 subjects diagnosed with mild to moderate AD in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from Baseline in the AD Assessment Scale-Cognitive subscale (ADAS-Cog), and global scores in the AD Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC). AC-1202 was compared to Placebo in several population groups, including: intention-to-treat (ITT), per protocol, and dosage compliant groups. Results were also stratified by APOE4 carriage status (a predefined analysis based on the epsilon 4 (E4) variant of the apolipoprotein E gene). This trial was registered with ClinicalTrials.gov, registry number NCT00142805, information available at http://clinicaltrials.gov/ct2/show/NCT00142805 Results AC-1202 significantly elevated a serum ketone body (β-hydroxybutyrate) 2 hours after administration when compared to Placebo. In each of the population groups, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45: 1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p = 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in dosage compliant. Among participants who did not carry the APOE4 allele (E4(-)), a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 and Day 90. In the ITT population, E4(-) participants (N = 55) administered AC-1202 had a significant 4.77 point difference in mean change from Baseline in ADAS-Cog scores at Day 45 (p = 0.0005) and a 3.36 point difference at Day 90 (p = 0.0148) compared to Placebo. In the per protocol population, E4(-) participants receiving AC-1202 (N = 37) differed from placebo by 5.73 points at Day 45 (p = 0.0027) and by 4.39 points at Day 90 (p = 0.0143). In the dosage compliant population, E4(-) participants receiving AC-1202 differed from placebo by 6.26 points at Day 45 (p = 0.0011, N = 38) and 5.33 points at Day 90 (p = 0.0063, N = 35). Furthermore, a significant pharmacologic response was observed between serum β-hydroxybutyrate levels and change in ADAS-Cog scores in E4(-) subjects at Day 90 (p = 0.008). Adverse events occurred more frequently in AC-1202 subjects, were primarily restricted to the gastrointestinal system, and were mainly mild to moderate in severity and transient in nature. Conclusion AC-1202 rapidly elevated serum ketone bodies in AD patients and resulted in significant differences in ADAS-Cog scores compared to the Placebo. Effects were most notable in APOE4(-) subjects who were dosage compliant.", "title": "Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial" }, { "docid": "MED-2940", "text": "In the past 3 decades, the total number of CT scans performed has grown exponentially. In 2007, > 70 million CT scans were performed in the United States. CT scan studies of the chest comprise a large portion of the CT scans performed today because the technology has transformed the management of common chest diseases, including pulmonary embolism and coronary artery disease. As the number of studies performed yearly increases, a growing fraction of the population is exposed to low-dose ionizing radiation from CT scan. Data extrapolated from atomic bomb survivors and other populations exposed to low-dose ionizing radiation suggest that CT scan-associated radiation may increase an individual's lifetime risk of developing cancer. This finding, however, is not incontrovertible. Because this topic has recently attracted the attention of both the scientific community and the general public, it has become increasingly important for physicians to understand the cancer risk associated with CT scan and be capable of engaging in productive dialogue with patients. This article reviews the current literature on the public health debate surrounding CT scan and cancer risk, quantifies radiation doses associated with specific studies, and describes efforts to reduce population-wide CT scan-associated radiation exposure. CT scan examinations of the chest, including CT scan pulmonary and coronary angiography, high-resolution CT scan, low-dose lung cancer screening, and triple rule-out CT scan, are specifically considered.", "title": "Radiation and chest CT scan examinations: what do we know?" }, { "docid": "MED-1256", "text": "BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.", "title": "A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption." }, { "docid": "MED-4004", "text": "Evidence suggests that monounsaturated and polyunsaturated fats facilitate greater absorption of carotenoids than saturated fats. However, the comparison of consuming a polyunsaturated fat source versus a saturated fat source on tomato carotenoid bioaccumulation has not been examined. The goal of this study was to determine the influence of coconut oil and safflower oil on tomato carotenoid tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat diet. Coconut oil feeding increased carotenoid concentrations among many compartments including total carotenoids in the serum (p = 0.0003), adrenal glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all-trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils. Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut oil enhanced tissue uptake of tomato carotenoids to a greater degree than safflower oil. These results may have been due to the large proportion of medium-chain fatty acids in coconut oil, which might have caused a shift in cholesterol flux to favor extrahepatic carotenoid tissue deposition.", "title": "Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower oil in the Mongolian gerbil ( Meriones unguiculatus )." }, { "docid": "MED-3199", "text": "It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®", "title": "Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters." }, { "docid": "MED-4608", "text": "The effects of drinking sodium-bicarbonated mineral water on cardiovascular risk in young men and women with moderate cardiovascular risk were studied. Eighteen young volunteers (total cholesterol levels >5.2 mmol/L) without any disease participated. The study consisted of two 8-week intervention periods. Subjects consumed, as supplement to their usual diet, 1 L/day control low mineral water, followed by 1 L/day bicarbonated mineral water (48 mmol/L sodium, 35 mmol/L bicarbonate and 17 mmol/L chloride). Determinations were performed at the end of the control water period and on Weeks 4 and 8 of the bicarbonated water period. Body weight, body mass index (BMI), blood pressure, dietary intake, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, apolipoprotein (Apo) A-I, Apo B, triacylgycerols, glucose, insulin, adiponectin, high-sensitivity C-reactive protein (hs-CRP), soluble adhesion molecules [soluble intercellular adhesion molecule (sICAM) and soluble vascular adhesion molecule (sVCAM)], sodium and chloride urinary excretion, and urine pH were measured. Dietary intake, body weight and BMI showed no significant variations. Systolic blood pressure decreased significantly after 4 weeks of bicarbonated water consumption, without significant differences between Weeks 4 and 8. After bicarbonated water consumption, significant reductions in total cholesterol (by 6.3%; P=.012), LDL cholesterol (by 10%; P=.001), total/HDL cholesterol (P=.004), LDL/HDL cholesterol (P=.001) and Apo B (P=.017) were observed. Serum triacylglycerol, Apo A-I, sICAM-1, sVCAM-1 and hs-CRP levels did not change. Serum glucose values tended to decrease during the bicarbonated water intervention (P=.056), but insulin levels did not vary. This sodium-bicarbonated mineral water improves lipid profile in moderately hypercholesterolemic young men and women and could therefore be applied in dietary interventions to reduce cardiovascular risk. Copyright © 2010 Elsevier Inc. All rights reserved.", "title": "Reduction in cardiovascular risk by sodium-bicarbonated mineral water in moderately hypercholesterolemic young adults." }, { "docid": "MED-3910", "text": "Background Figs are a rich source of soluble fiber. We evaluated the effect of consuming dried California Mission figs on serum lipids in hyperlipidemic adults. Methods In a crossover trial men and women aged 30–75 years with elevated low-density lipoprotein cholesterol (100–189 mg/dl) were randomized to add dried California Mission figs (120 g/day) to their usual diet for 5 weeks or eat their usual diet for 5 weeks, then crossed over to the other condition for another 5 weeks. Six 24-hour dietary recalls were obtained. Results Low- and high-density lipoprotein cholesterol and triglyceride concentrations did not differ between usual and figs-added diets (Bonferroni-corrected p > 0.017), while total cholesterol tended to increase with fig consumption (p = 0.02). Total cholesterol increased in participants (n = 41) randomized to usual followed by figs-added diet (p = 0.01), but remained unchanged in subjects (n = 42) who started with figs-added followed by usual diet (p = 0.4). During the figs-added diet, soluble fiber intake was 12.6 ± 3.7 versus 8.2 ± 4.1 g/day in the usual diet (p < 0.0001). Sugar intake increased from 23.4 ± 6.5 to 32.2 ± 6.3% of kcal in the figs-added diet (p < 0.0001). Body weight did not change (p = 0.08). Conclusions Daily consumption of figs did not reduce low-density lipoprotein cholesterol. Triglyceride concentrations were not significantly changed despite an increase in sugar intake.", "title": "Effect of Consumption of Dried California Mission Figs on Lipid Concentrations" }, { "docid": "MED-3000", "text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.", "title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer." }, { "docid": "MED-2439", "text": "While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts one’s risk for this disease. More recently, specific food components have been identified which are uniquely beneficial in mitigating the risk of specific cancer subtypes. Plant sterols are well known for their effects on blood cholesterol levels, however research into their potential role in mitigating cancer risk remains in its infancy. As outlined in this review, the cholesterol modulating actions of plant sterols may overlap with their anti-cancer actions. Breast cancer is the most common malignancy affecting women and there remains a need for effective adjuvant therapies for this disease, for which plant sterols may play a distinctive role.", "title": "Plant Sterols as Anticancer Nutrients: Evidence for Their Role in Breast Cancer" }, { "docid": "MED-1430", "text": "OBJECTIVE: Compare levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) among vegetarians and omnivores. METHODS: Blood samples were collected from 76 individuals--both males and females--separated in four different diet groups: omnivores, lacto-ovo vegetarians, lacto vegetarians, and restricted vegetarians (or vegans). Dosing was done for: TC, LDL, HDL and TG. RESULTS: Significant difference was reported for TC, LDL and TG levels among the samples. Higher levels were reported by omnivores, with decreased levels for vegetarians as animal products were restricted, with lowest levels having been reported by vegans. Mean and standard deviation for TC were 208.09 +/- 49.09 mg/dl in the group of omnivores, and 141.06 +/- 30.56 mg/dl in the group of vegans (p < 0.001). LDL values for omnivores and vegans were respectively: 123.43 +/- 42.67 mg/dl and 69.28 +/- 29.53 mg/dl (p < 0.001). As for TG, those values were 155.68 +/- 119.84 mg/dl and 81.67 +/- 81.90 mg/dl (p < 0.01). As for HDL level no difference was reported between the samples, but HDL/TC ratio was significantly higher in vegans (p = 0.01). CONCLUSION: Vegetarian diet was associated to lower levels of TG, TC and LDL as compared to the diet of omnivores.", "title": "Vegetarian diet and cholesterol and triglycerides levels." }, { "docid": "MED-4834", "text": "Soft drinks can be a major source of sucrose, which may influence serum lipid concentration. We have examined the association between intake frequency of various types of soft drinks and the concentration of serum triglycerides (TG) and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol in the cross-sectional Oslo Health Study. A total of 14 188 subjects of the altogether 18,770 participants of the study had data on intake frequency of colas and non-colas, with or without sugar. The population sample consisted of both sexes and 3 age groups: group 1 (30 years of age), group 2 (40 and 45 years of age), and group 3 (59-60 years of age). In both sexes, HDL decreased and TG increased significantly (p < 0.001) with increasing intake frequency of colas. In contrast, no consistent associations were found between the reported intake of non-cola soft drinks and the serum lipids. We found no significant differences related to the reported presence or absence of sugar in the soft drinks. In multiple linear regression analyses, the colas vs. serum lipid associations prevailed (p < 0.001) after including 13 possible confounders: sex; age group; time since last meal; physical activity; intake of alcohol, coffee, cheese, fruit and (or) berries, and fatty fish; smoking; length of education; use of cholesterol-lowering drugs; and intake of non-colas. Thus, the self-reported intake frequency of colas, but not other soft drinks, was negatively associated with serum HDL, and positively associated with TG and LDL.", "title": "Cola intake and serum lipids in the Oslo Health Study." }, { "docid": "MED-3208", "text": "This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight. Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal), but differed in energy density. We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro, Brazil. Forty-nine women, ages ranging from 30 to 50 years, with body mass index (BMI)>25 kg/m2, were randomly chosen to add three apples (0.63 kcal/g energy density) or three pears (0.64 kcal/g energy density) or three oat cookies (3.7 kcal/g energy density) to their usual diet for 10 weeks. Fiber composition was similar ( approximately 6g). Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures. Results showed a significant decrease in the energy density during the follow-up (-1.23 kcal/g, p<0.04, and -1.29 kcal/g, p<0.05) for apples and pears, respectively, compared to the oat group. The energy intake also decreased significantly (-25.05 and -19.66 kcal/day) for the apple and pear group, respectively, but showed a small increase (+0.93) for the oat group. Apples and pears were also associated (p<0.001) with weight reduction (-0.93 kg for the apple and -0.84 for the pear group), whereas weight was unchanged (+0.21; p=0.35) in the oat group. Results suggest that energy densities of fruits, independent of their fiber amount can reduce energy consumption and body weight over time.", "title": "A low-energy-dense diet adding fruit reduces weight and energy intake in women." }, { "docid": "MED-1932", "text": "There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.", "title": "Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study" }, { "docid": "MED-4541", "text": "Objective To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes. Design Systematic review and meta-analysis of observational studies. Data sources Searches of Medline and Embase in September 2010. Study selection Observational studies that directly compared the risk of cardiovascular outcomes for rosiglitazone and pioglitazone among patients with type 2 diabetes mellitus were included. Data extraction Random effects meta-analysis (inverse variance method) was used to calculate the odds ratios for cardiovascular outcomes with thiazolidinedione use. The I2 statistic was used to assess statistical heterogeneity. Results Cardiovascular outcomes from 16 observational studies (4 case-control studies and 12 retrospective cohort studies), including 810 000 thiazolidinedione users, were evaluated after a detailed review of 189 citations. Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n=15 studies; odds ratio 1.16, 95% confidence interval 1.07 to 1.24; P<0.001; I2=46%), congestive heart failure (n=8; 1.22, 1.14 to 1.31; P<0.001; I2=37%), and death (n=8; 1.14, 1.09 to 1.20; P<0.001; I2=0%). Numbers needed to treat to harm (NNH), depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100 000 patients who receive rosiglitazone rather than pioglitazone. Conclusion Among patients with type 2 diabetes, use of rosiglitazone is associated with significantly higher odds of congestive heart failure, myocardial infarction, and death relative to pioglitazone in real world settings.", "title": "Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies" }, { "docid": "MED-3821", "text": "Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.", "title": "Development of a Polyamine Database for Assessing Dietary Intake" }, { "docid": "MED-4002", "text": "The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences (WC) >88 cm (abdominal obesity) were investigated. The randomised, double-blind, clinical trial involved 40 women aged 20-40 years. Groups received daily dietary supplements comprising 30 mL of either soy bean oil (group S; n = 20) or coconut oil (group C; n = 20) over a 12-week period, during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day. Data were collected 1 week before (T1) and 1 week after (T2) dietary intervention. Energy intake and amount of carbohydrate ingested by both groups diminished over the trial, whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged. At T1 there were no differences in biochemical or anthropometric characteristics between the groups, whereas at T2 group C presented a higher level of HDL (48.7 +/- 2.4 vs. 45.00 +/- 5.6; P = 0.01) and a lower LDL:HDL ratio (2.41 +/- 0.8 vs. 3.1 +/- 0.8; P = 0.04). Reductions in BMI were observed in both groups at T2 (P < 0.05), but only group C exhibited a reduction in WC (P = 0.005). Group S presented an increase (P < 0.05) in total cholesterol, LDL and LDL:HDL ratio, whilst HDL diminished (P = 0.03). Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity.", "title": "Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity." }, { "docid": "MED-2517", "text": "Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.", "title": "mTOR is a key modulator of ageing and age-related disease" }, { "docid": "MED-2212", "text": "With the republication of Grant (18), the first paper providing epidemiologic evidence linking diet to the development of Alzheimer's disease (AD), it is an appropriate time to review the findings and hypotheses therein in light of the subsequent literature. The main findings, that dietary fat and energy in old age are high risk factors, while fish and cereals are risk-reduction factors, have been supported in various recent epidemiologic studies. Diet contributes to the development of AD through modulating oxidative stress and inflammation, which is also linked to oxidative stress, but may also arise from series 2 prostaglandins. Thus, as one ages, dietary modifications and additional supplements designed to reduce free radical production and inflammation provide a significant measure of reduction in risk for the development of AD.", "title": "Dietary links to Alzheimer's disease: 1999 update." }, { "docid": "MED-4831", "text": "Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.", "title": "Effects of plant-based diets on plasma lipids." }, { "docid": "MED-3143", "text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.", "title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial." }, { "docid": "MED-1929", "text": "BACKGROUND This study examined the effects of brief daily yogic meditation on mental health, cognitive functioning, and immune cell telomerase activity in family dementia caregivers with mild depressive symptoms. METHODS Thirty-nine family dementia caregivers (mean age 60.3 years old (SD=10.2)) were randomized to practicing Kirtan Kriya or listening to relaxation music for 12 minutes per day for eight weeks. The severity of depressive symptoms, mental and cognitive functioning were assessed at baseline and follow-up. Telomerase activity in peripheral blood mononuclear cells (PMBC) was examined in peripheral PBMC pre- and post-intervention. RESULTS The meditation group showed significantly lower levels of depressive symptoms and greater improvement in mental health and cognitive functioning compared to the relaxation group. In the meditation group, 65.2% showed 50% improvement on the Hamilton Depression Rating scale and 52% of the participants showed 50% improvement on the Mental Health Composite Summary score (MCS) of the SF-36 scale; compared to 31.2% and 19% respectively in the relaxation group (pp<0.05). The meditation group showed 43% improvement in telomerase activity compared to 3.7% in the relaxation group (p=0.05). CONCLUSION This pilot study found that brief daily meditation practices by family dementia caregivers can lead to improved mental and cognitive functioning, and lower levels of depressive symptoms. This improvement is accompanied by an increase in telomerase activity suggesting improvement in stress-induced cellular aging. These results need to be confirmed in a larger sample.", "title": "A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: Effects on mental health, cognition, and telomerase activity" }, { "docid": "MED-1921", "text": "Dietary factors, including dietary fat, may affect the biological aging process, as reflected by the shortening of telomere length (TL), by affecting levels of oxidative stress and inflammatory responses. We examined the direct relations of total and types of dietary fats and fat-rich foods to peripheral leukocyte TL. In 4029 apparently healthy postmenopausal women who participated in the Women’s Health Initiative, intakes of total fat, individual fatty acids, and fat-rich foods were assessed by a questionnaire. TL was measured by quantitative polymerase chain reaction. Intake of short-to-medium-chain saturated fatty acids (SMSFAs; aliphatic tails of ≤12 carbons) was inversely associated with TL. Compared with participants in other quartiles of SMSFA intake, women who were in the highest quartile (median: 1.29% of energy) had shorter TLs [mean: 4.00 kb (95% CI: 3.89, 4.11 kb)], whereas women in the lowest quartile of intake (median: 0.29% of energy) had longer TLs [mean: 4.13 kb (95% CI: 4.03, 4.24 kb); P-trend = 0.046]. Except for lauric acid, all other individual SMSFAs were inversely associated with TL (P < 0.05). In isoenergetic substitution models, the substitution of 1% of energy from SMSFAs with any other energy source was associated with 119 bp longer TLs (95% CI: 21, 216 bp). Intakes of nonskim milk, butter, and whole-milk cheese (major sources of SMSFAs) were all inversely associated with TL. No significant associations were found with long-chain saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. In conclusion, we found that higher intakes of SMSFAs and SMSFA-rich foods were associated with shorter peripheral leukocyte TL among postmenopausal women. These findings suggest the potential roles of SMSFAs in the rate of biological aging.", "title": "Intake of Small-to-Medium-Chain Saturated Fatty Acids Is Associated with Peripheral Leukocyte Telomere Length in Postmenopausal Women" }, { "docid": "MED-3205", "text": "Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.", "title": "Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and ..." }, { "docid": "MED-1887", "text": "Some practitioners use advanced lipoprotein analysis with the goal of better predicting risk and individualizing lifestyle and drug therapy for cardiovascular prevention. Unfortunately, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle number and size, other lipoprotein subfractionation, apolipoproteins B and A, and lipoprotein(a) have not yet met current standards for biomarker evaluation, and it remains to be determined whether these tests incrementally add to cardiovascular risk predicted by traditional risk factors. More importantly, it has yet to be determined whether treatment strategies guided by, or targeting, these measures improve cardiovascular outcomes. Drug therapies known to alter advanced lipoprotein analysis parameters, specifically niacin and fenofibrate, have not been shown to additionally reduce cardiovascular risk in recent randomized trials of high-risk patients treated with statin therapy. These findings suggest advanced lipoprotein analysis-guided strategies may not further reduce cardiovascular events and could lead to increased adverse effects and costs; this approach needs further research to establish its role in individualizing therapies for cardiovascular prevention. In contrast, a large body of evidence supports focusing on LDL cholesterol reduction and intensification of statin therapy to reduce cardiovascular risk. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "What is the role of advanced lipoprotein analysis in practice?" }, { "docid": "MED-4249", "text": "BACKGROUND AND AIMS: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. METHODS AND RESULTS: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance. CONCLUSION: The results confirm the cholesterol lowering properties of nut-enriched diets. They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content, which clearly deserves further study. Copyright © 2010 Elsevier B.V. All rights reserved.", "title": "Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers." }, { "docid": "MED-2528", "text": "OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat \"American diet.\" CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.", "title": "Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study." }, { "docid": "MED-1934", "text": "Objective Investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on leukocyte telomere length in postmenopausal women. Design and Methods 439 overweight or obese women (50–75 y) were randomized to: i) dietary weight loss (N=118); ii) aerobic exercise (N=117), iii) diet + exercise (N=117), or iv) control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous aerobic activity. Fasting blood samples were taken at baseline and 12 months. DNA was extracted from isolated leukocytes and telomere length was measured by quantitative-polymerase chain reaction (qPCR). Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results Baseline telomere length was inversely associated with age (r=−0.12 p<0.01) and positively associated with maximal oxygen uptake (r=0.11, p=0.03), but not with BMI or %body fat. Change in telomere length was inversely correlated with baseline telomere length (r=−0.47, p<0.0001). No significant difference in leukocyte telomere length was detected in any intervention group compared to controls, nor was the magnitude of weight loss associated with telomere length at 12 months. Conclusions Twelve-months of dietary weight loss and exercise did not change telomere length in postmenopausal women.", "title": "Independent and Combined Effects of Dietary Weight Loss and Exercise on Leukocyte Telomere Length in Postmenopausal Women" }, { "docid": "MED-2184", "text": "Objectives. We examined the effects of state-level unemployment rates during the recession of 2008 on patterns of home food preparation and away-from-home (AFH) eating among low-income and minority populations. Methods. We analyzed pooled cross-sectional data on 118 635 adults aged 18 years or older who took part in the American Time Use Study. Multinomial logistic regression models stratified by gender were used to evaluate the associations between state-level unemployment, poverty, race/ethnicity, and time spent cooking, and log binomial regression was used to assess respondents’ AFH consumption patterns. Results. High state-level unemployment was associated with only trivial increases in respondents’ cooking patterns and virtually no change in their AFH eating patterns. Low-income and racial/ethnic minority groups were not disproportionately affected by the recession. Conclusions. Even during a major economic downturn, US adults are resistant to food-related behavior change. More work is needed to understand whether this reluctance to change is attributable to time limits, lack of knowledge or skill related to food preparation, or lack of access to fresh produce and raw ingredients.", "title": "Resistant to the Recession: Low-Income Adults’ Maintenance of Cooking and Away-From-Home Eating Behaviors During Times of Economic Turbulence" }, { "docid": "MED-2442", "text": "A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.", "title": "Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis." }, { "docid": "MED-2384", "text": "BACKGROUND: Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS: The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS: Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION: Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit. Copyright © 2013 National Lipid Association. All rights reserved.", "title": "Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects." }, { "docid": "MED-4352", "text": "Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.", "title": "Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits." }, { "docid": "MED-2595", "text": "Nuts are an integral part of the Mediterranean food patterns, and their incorporation into the regular diets of human beings is believed to provide many health benefits. The recent recognition of nuts as \"heart-healthy\" foods by the U.S. Food and Drug Administration has given a major boost to the positive image of nuts. Nut consumption has been associated with several health benefits, such as antioxidant, hypocholesterolemic, cardioprotective, anticancer, anti-inflammatory, and antidiabetic benefits, among other functional properties. However, although nuts possess these many health benefits, their consumption has been hampered by a lack of adequate information regarding those benefits. In addition, because nuts are energy-dense foods with high-fat content, there is a misconception among consumers that increased consumption may lead to unwanted gain in body weight with the risk of developing overweight/obesity. Nonetheless, available epidemiologic studies and short-term controlled feeding trials have supported the theory that the inclusion of nuts in the typical diet does not induce weight gain, despite an expected increase in total caloric intake. To address the misperception about nuts and body weight gain, the present review focuses mainly on the relation between nut consumption and body weight gain, in the context of the many health benefits of nuts. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Health benefits of nut consumption with special reference to body weight control." }, { "docid": "MED-2513", "text": "Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.", "title": "Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life" }, { "docid": "MED-2885", "text": "OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.", "title": "Ultraviolet phototoxicity to the retina." }, { "docid": "MED-3141", "text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.", "title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome." }, { "docid": "MED-2217", "text": "OBJECTIVE: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.", "title": "Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study." }, { "docid": "MED-2078", "text": "Platelet hyperactivity is one of the most important factors responsible for the incidence of cardiovascular disease. There are many nutritive and non-nutritive compounds present in the diet which may affect platelet function in various ways. Recent discovery of anti-platelet factors in plants, vegetables and fruits provides a new dietary means for a long-term strategy to favorably modify human blood platelet activity. This review summarises the effects of these dietary components on human platelet function both in vitro and in vivo.", "title": "Dietary components and human platelet activity." }, { "docid": "MED-4028", "text": "This paper aims to provide dental health professionals with practical advice to pass on to patients about diet and dental health. Sugars are the most important dietary factor contributing to dental caries. Different foods carry different dental health risks; those containing non-milk, extrinsic sugars are potentially the most damaging. In the UK, sugared soft drinks and confectionery contribute approximately 50% to total intake of non-milk extrinsic sugars. Patients should be encouraged to reduce the frequency of intake of sugary foods. Intake of acidic foods and drinks contributes to dental erosion and consumption of such foods should also be limited. Dietary advice to dental patients should be positive and personalized if possible and can be in line with dietary recommendations for general health. These are to increase the consumption of starchy staple foods (eg bread, potatoes and unsweetened cereals), vegetables and fruit and to reduce the consumption of sugary and fatty foods.", "title": "Dietary advice in dental practice." }, { "docid": "MED-1884", "text": "We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.", "title": "Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge." }, { "docid": "MED-3197", "text": "Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.", "title": "Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins" }, { "docid": "MED-4000", "text": "Coconut oil is a common edible oil in many countries, and there is mixed evidence for its effects on lipid profiles and cardiovascular disease risk. Here we examine the association between coconut oil consumption and lipid profiles in a cohort of 1,839 Filipino women (age 35–69 years) participating in the Cebu Longitudinal Health and Nutrition Survey, a community based study in Metropolitan Cebu City. Coconut oil intake was measured as individual coconut oil intake calculated using two 24-hour dietary recalls (9.54 ± 8.92 grams). Cholesterol profiles were measured in plasma samples collected after an overnight fast. Mean lipid values in this sample were total cholesterol (TC) (186.52 ± 38.86 mg/dL), high density lipoprotein cholesterol (HDL-c) (40.85 ± 10.30 mg/dL), low density lipoprotein cholesterol (LDL-c) (119.42 ± 33.21 mg/dL), triglycerides (130.75 ± 85.29 mg/dL) and the TC/HDL ratio (4.80 ± 1.41). Linear regression models were used to estimate the association between coconut oil intake and each plasma lipid outcome after adjusting for total energy intake, age, body mass index (BMI), number of pregnancies, education, menopausal status, household assets and urban residency. Dietary coconut oil intake was positively associated with HDL-c levels.", "title": "Coconut oil predicts a beneficial lipid profile in pre-menopausal women in the Philippines" }, { "docid": "MED-2944", "text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.", "title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States" }, { "docid": "MED-1882", "text": "BACKGROUND: Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. METHODS AND RESULTS: This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles (-5%) while raising numbers of HDL particles (10%) and small HDL subclass particles (21%). Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant, independent predictors of new CHD events. For total LDL and HDL particles, odds ratios predicting CHD benefit were 1.28 (95% CI, 1.12 to 1.47) and 0.71 (95% CI, 0.61 to 0.81), respectively. Mean LDL and HDL particle sizes were not associated with CHD events. CONCLUSIONS: The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.", "title": "Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy i..." }, { "docid": "MED-2592", "text": "Background Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks. Results Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups. Conclusion Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.", "title": "Effects of pistachios on body weight in Chinese subjects with metabolic syndrome" }, { "docid": "MED-4085", "text": "The effect of a strict, low-salt, uncooked vegan diet rich in lactobacteria on symptoms in 18 fibromyalgia patients during and after a 3-month intervention period in an open, non-randomized controlled study was evaluated. As control 15 patients continued their omnivorous diet. The groups did not differ significantly from each other in the beginning of the study in any other parameters except in pain and urine sodium. The results revealed significant improvements in Visual analogue scale of pain (VAS) (p=0.005), joint stiffness (p=0.001), quality of sleep (p=0.0001), Health assessment questionnaire (HAQ) (p=0.031), General health questionnaire (GHQ) (p=0.021), and a rheumatologist's own questionnaire (p=0.038). The majority of patients were overweight to some extent at the beginning of the study and shifting to a vegan food caused a significant reduction in body mass index (BMI) (p=0.0001). Total serum cholesterol showed a statistically significant lowering (p=0.003). Urine sodium dropped to 1/3 of the beginning values (p=0.0001) indicating good diet compliance. It can be concluded that vegan diet had beneficial effects on fibromyalgia symptoms at least in the short run.", "title": "Vegan diet alleviates fibromyalgia symptoms." }, { "docid": "MED-1258", "text": "Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.", "title": "The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia." }, { "docid": "MED-2898", "text": "PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.", "title": "Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population." }, { "docid": "MED-2180", "text": "Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.", "title": "Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study" }, { "docid": "MED-2379", "text": "Objectives Metabolic syndrome is a precursor of diabetes and cardiovascular disease (CVD). Walnut ingestion has been shown to reduce CVD risk indices in diabetes. This randomized controlled crossover trial was performed to investigate the effects of daily walnut consumption on endothelial function and other biomarkers of cardiac risk in a population of overweight individuals with visceral adiposity. Methods Forty-six overweight adults (average age, 57.4 years; 28 women, 18 men) with elevated waist circumference and 1 or more additional signs of metabolic syndrome were randomly assigned to two 8-week sequences of walnut-enriched ad libitum diet and ad libitum diet without walnuts, which were separated by a 4-week washout period. The primary outcome measure was the change in flow-mediated vasodilation (FMD) of the brachial artery. Secondary measures included serum lipid panel, fasting glucose and insulin, Homeostasis Model Assessment–Insulin Resistance values, blood pressure, and anthropometric measures. Results FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet (1.4% ± 2.4% versus 0.3% ± 1.5%; p = 0.019). Beneficial trends in systolic blood pressure reduction were seen, and maintenance of the baseline anthropometric values was also observed. Other measures were unaltered. Conclusion Daily ingestion of 56 g of walnuts improves endothelial function in overweight adults with visceral adiposity. The addition of walnuts to the diet does not lead to weight gain. Further study of the potential role of walnut intake in diabetes and CVD prevention is warranted.", "title": "Effects of Walnuts on Endothelial Function in Overweight Adults with Visceral Obesity: A Randomized, Controlled, Crossover Trial" }, { "docid": "MED-3907", "text": "Background This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus. Methods Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. The glycemic indices were determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Statistical analyses were performed using the Mann-Whitney U test and repeated measures analysis of variance. Results Mean glycemic indices ± SEM of the dates for the healthy individuals were 54.0 ± 6.1, 53.5 ± 8.6, 46.3 ± 7.1, 49.1 ± 3.6 and 55.1 ± 7.7 for Fara'd, Lulu, Bo ma'an, Dabbas and Khalas, respectively. Corresponding values for those with type 2 diabetes were very similar (46.1 ± 6.2, 43.8 ± 7.7, 51.8 ± 6.9, 50.2 ± 3.9 and 53.0 ± 6.0). There were no statistically significant differences in the GIs between the control and the diabetic groups for the five types of dates, nor were there statistically significant differences among the dates' GIs (df = 4, F = 0.365, p = 0.83). Conclusion The results show low glycemic indices for the five types of dates included in the study and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. These findings point to the potential benefits of dates for diabetic subjects when used in a healthy balanced diet. Trial Registration Number ClinicalTrials.gov NCT01307904", "title": "Glycemic indices of five varieties of dates in healthy and diabetic subjects" }, { "docid": "MED-2852", "text": "AIMS/HYPOTHESIS: The aim of this study was to prospectively examine whether dietary patterns are related to risk of gestational diabetes mellitus (GDM). METHODS: This prospective cohort study included 13,110 women who were free of cardiovascular disease, cancer, type 2 diabetes and history of GDM. Subjects completed a validated semi-quantitative food frequency questionnaire in 1991, and reported at least one singleton pregnancy between 1992 and 1998 in the Nurses' Health Study II. Two major dietary patterns (i.e. 'prudent' and 'Western') were identified through factor analysis. The prudent pattern was characterised by a high intake of fruit, green leafy vegetables, poultry and fish, whereas the Western pattern was characterised by high intake of red meat, processed meat, refined grain products, sweets, French fries and pizza. RESULTS: We documented 758 incident cases of GDM. After adjustment for age, parity, pre-pregnancy BMI and other covariates, the relative risk (RR) of GDM, comparing the highest with the lowest quintile of the Western pattern scores, was 1.63 (95% CI 1.20-2.21; p (trend)=0.001), whereas the RR comparing the lowest with the highest quintile of the prudent pattern scores was 1.39 (95% CI 1.08-1.80; p (trend)=0.018). The RR for each increment of one serving/day was 1.61 (95% CI 1.25-2.07) for red meat and 1.64 (95% CI 1.13-2.38) for processed meat. CONCLUSIONS/INTERPRETATION: These findings suggest that pre-pregnancy dietary patterns may affect women's risk of developing GDM. A diet high in red and processed meat was associated with a significantly elevated risk.", "title": "A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus." }, { "docid": "MED-2884", "text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.", "title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women." }, { "docid": "MED-1554", "text": "BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB s, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.", "title": "Reduced or modified dietary fat for preventing cardiovascular disease." }, { "docid": "MED-3391", "text": "Aim: To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED). Methods: Data were collated from 67 double-blind placebo-controlled (DBPC) trials (> 14,000 men) conducted by the manufacturer and from the manufacturer’s postmarketing safety database (39,277 patients). The DBPC data were stratified by dose, starting dose and age (≥ 65 and ≥ 75 years). Special safety topics included cardiovascular risk, priapism, non-arteritic anterior ischaemic optic neuropathy (NAION), impaired renal and hepatic function, drug interactions (i.e. nitrates, cytochrome P3A4 inhibitors, other ED therapies and α-blockers) and incorrect use. Results: Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged ≥ 65 years, and in those aged ≥ 75 years. Analyses of the databases did not reveal any causal link between sildenafil and cardiovascular events, or any new safety risks relating to cardiovascular events, priapism, NAION, hearing loss or drug interactions. In the small number of men with moderate impairment of renal function or hepatic function who were treated with sildenafil in DBPC trials, the safety profile was similar to that in men with no impairment of renal or hepatic function. Overdose with sildenafil was rare in the ED population. No new safety issues, emerging trends or adverse reactions were identified in conjunction with overdose, dependence, abuse or misuse. Conclusion: This collated review confirms generally the good tolerability and established safety profile of sildenafil 50 and 100 mg in men with ED and reveals no new safety issues.", "title": "Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database" }, { "docid": "MED-2586", "text": "A systematic review and meta-analysis were carried out to study the effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases). A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients, showed the LCD to be associated with significant decreases in body weight (-7.04 kg [95% CI -7.20/-6.88]), body mass index (-2.09 kg m(-2) [95% CI -2.15/-2.04]), abdominal circumference (-5.74 cm [95% CI -6.07/-5.41]), systolic blood pressure (-4.81 mm Hg [95% CI -5.33/-4.29]), diastolic blood pressure (-3.10 mm Hg [95% CI -3.45/-2.74]), plasma triglycerides (-29.71 mg dL(-1) [95% CI -31.99/-27.44]), fasting plasma glucose (-1.05 mg dL(-1) [95% CI -1.67/-0.44]), glycated haemoglobin (-0.21% [95% CI -0.24/-0.18]), plasma insulin (-2.24 micro IU mL(-1) [95% CI -2.65/-1.82]) and plasma C-reactive protein, as well as an increase in high-density lipoprotein cholesterol (1.73 mg dL(-1) [95%CI 1.44/2.01]). Low-density lipoprotein cholesterol and creatinine did not change significantly, whereas limited data exist concerning plasma uric acid. LCD was shown to have favourable effects on body weight and major cardiovascular risk factors; however the effects on long-term health are unknown. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.", "title": "Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors." }, { "docid": "MED-3790", "text": "Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.", "title": "Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression" }, { "docid": "MED-4835", "text": "OBJECTIVE: Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone. DESIGN: Randomized, parallel-arm, controlled trial. SUBJECTS/SETTING: Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations. INTERVENTION: Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy ( approximately 500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. MAIN OUTCOME MEASURES: Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12. RESULTS: LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (-8.7+/-1.0 vs -4.3+/-1.1%, P=0.005). Total cholesterol (-5.4+/-0.8 vs -2.9+/-0.9%, P=0.038) and non-high-density lipoprotein-cholesterol (-6.3+/-1.0 vs -3.3+/-1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (-2.2+/-0.3 vs -1.7+/-0.3 kg, P=0.325), but waist circumference decreased more (-3.3+/-0.4 vs -1.9+/-0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group. CONCLUSIONS: Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference. Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.", "title": "Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overw..." }, { "docid": "MED-4538", "text": "The present study evaluated the anti-hyperglycemic and lipid-lowering properties of Emblica officinalis Gaertn. fruit in normal and diabetic human volunteers. The results indicated a significant decrease (P < 0.05) in fasting and 2-h post-prandial blood glucose levels on the 21st day in both normal and diabetic subjects receiving 1, 2 or 3 g E. officinalis powder per day as compared with their baseline values. Significant (P < 0.05) decreases were also observed in total cholesterol and triglycerides in both normal and diabetic volunteers on day 21 that were given either 2 or 3 g E. officinalis powder per day. However, diabetic volunteers receiving only 3 g E. officinalis powder exhibited a significant (P < 0.05) decrease in total lipids on day 21. Both normal and diabetic volunteers receiving 2 or 3 g E. officinalis powder significantly (P < 0.05) improved high-density lipoprotein-cholesterol and lowered low-density lipoprotein-cholesterol levels.", "title": "Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipid profile of normal subjects and type 2 diabetic patients." }, { "docid": "MED-2211", "text": "BACKGROUND: China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. METHODS: In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. FINDINGS: Our search returned 12,642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340,247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254,367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0-44·4) at 65-69 years, and 42·1% (0·0-88·9) at age 95-99 years. In 2010 prevalence was 2·6% (0·0-28·2) at age 65-69 years and 60·5% (39·7-81·3) at age 95-99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22-5·14) in 1990, 5·62 million (4·42-6·82) in 2000, and 9·19 million (5·92-12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15-2·71) in 1990, 3·71 million (2·84-4·58) people in 2000, and 5·69 million (3·85-7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20,157 healthy controls, who were followed up for 3-7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74-2·45). INTERPRETATION: Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. FUNDING: Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia-China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis." }, { "docid": "MED-5012", "text": "This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.", "title": "The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol." }, { "docid": "MED-1609", "text": "To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.", "title": "High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults." }, { "docid": "MED-2510", "text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.", "title": "Comparative and meta-analytic insights into life extension via dietary restriction." }, { "docid": "MED-3206", "text": "To study the effects of grapefruit and grapefruit products on body weight and metabolic syndrome, 91 obese patients were randomized to either placebo capsules and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces (207 mL) of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or half of a fresh grapefruit with a placebo capsule three times a day before each meal. Metabolic syndrome parameters were measured at the beginning and end of 12 weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit juice group had lost 1.5 kg, the grapefruit capsule group had lost 1.1 kg, and the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly more weight than the placebo group (P < .05). A secondary analysis of those with the metabolic syndrome in the four treatment groups demonstrated a significantly greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice groups compared with placebo (P < .02). There was also a significant reduction in 2-hour post-glucose insulin level in the grapefruit group compared with placebo. Half of a fresh grapefruit eaten before meals was associated with significant weight loss. In metabolic syndrome patients the effect was also seen with grapefruit products. Insulin resistance was improved with fresh grapefruit. Although the mechanism of this weight loss is unknown it would appear reasonable to include grapefruit in a weight reduction diet.", "title": "The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome." }, { "docid": "MED-4036", "text": "Oral health is related to diet in many ways, for example, nutritional influences on craniofacial development, oral cancer and oral infectious diseases. Dental diseases impact considerably on self-esteem and quality of life and are expensive to treat. The objective of this paper is to review the evidence for an association between nutrition, diet and dental diseases and to present dietary recommendations for their prevention. Nutrition affects the teeth during development and malnutrition may exacerbate periodontal and oral infectious diseases. However, the most significant effect of nutrition on teeth is the local action of diet in the mouth on the development of dental caries and enamel erosion. Dental erosion is increasing and is associated with dietary acids, a major source of which is soft drinks. Despite improved trends in levels of dental caries in developed countries, dental caries remains prevalent and is increasing in some developing countries undergoing nutrition transition. There is convincing evidence, collectively from human intervention studies, epidemiological studies, animal studies and experimental studies, for an association between the amount and frequency of free sugars intake and dental caries. Although other fermentable carbohydrates may not be totally blameless, epidemiological studies show that consumption of starchy staple foods and fresh fruit are associated with low levels of dental caries. Fluoride reduces caries risk but has not eliminated dental caries and many countries do not have adequate exposure to fluoride. It is important that countries with a low intake of free sugars do not increase intake, as the available evidence shows that when free sugars consumption is <15-20 kg/yr ( approximately 6-10% energy intake), dental caries is low. For countries with high consumption levels it is recommended that national health authorities and decision-makers formulate country-specific and community-specific goals for reducing the amount of free sugars aiming towards the recommended maximum of no more than 10% of energy intake. In addition, the frequency of consumption of foods containing free sugars should be limited to a maximum of 4 times per day. It is the responsibility of national authorities to ensure implementation of feasible fluoride programmes for their country.", "title": "Diet, nutrition and the prevention of dental diseases." }, { "docid": "MED-3209", "text": "The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.", "title": "Can grapefruit juice influence ethinylestradiol bioavailability?" }, { "docid": "MED-2888", "text": "Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.", "title": "Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial." }, { "docid": "MED-5112", "text": "Background It has been postulated that a diet high in legumes may be beneficial for the prevention of type 2 diabetes mellitus (type 2 DM). However, data linking type 2 DM risk and legume intake are limited. Objective The objective of the study was to examine the association between legume and soy food consumption and self-reported type 2 DM. Design The study was conducted in a population-based prospective cohort of middle-aged Chinese women. We followed 64 227 women with no history of type 2 DM, cancer, or cardiovascular disease at study recruitment for an average of 4.6 y. Participants completed in-person interviews that collected information on diabetes risk factors, including dietary intake and physical activity in adulthood. Anthropometric measurements were taken. Dietary intake was assessed with a validated food-frequency questionnaire at the baseline survey and at the first follow-up survey administered 2–3 y after study recruitment. Results We observed an inverse association between quintiles of total legume intake and 3 mutually exclusive legume groups (peanuts, soybeans, and other legumes) and type 2 DM incidence. The multivariate-adjusted relative risk of type 2 DM for the upper quintile compared with the lower quintile was 0.62 (95% CI: 0.51, 0.74) for total legumes and 0.53 (95% CI: 0.45, 0.62) for soybeans. The association between soy products (other than soy milk) and soy protein consumption (protein derived from soy beans and their products) with type 2 DM was not significant. Conclusions Consumption of legumes, soybeans in particular, was inversely associated with the risk type 2 DM.", "title": "Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai Women’s Health Study" }, { "docid": "MED-1611", "text": "A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.", "title": "Latest insights into the risk of cancer in diabetes" }, { "docid": "MED-2700", "text": "Blood components, especially hemoglobin, are powerful promoters of lipid oxidation and may decrease the shelf life of meat products. Therefore, this study examined different slaughter techniques to determine their effects on pH (24 h), color (Lab* values at 24 h), lipid oxidation, residual hemoglobin concentration (24 h), and sensory evaluation (d 1 and 4 postmortem; PM) in broiler breast fillets. The treatments included 1) CO(2) slaughter and not bled, 2) no stunning and bled, 3) electrical stunning (ES) and bled, 4) CO(2) stunning and bled, and 5) ES and decapitation. The birds were conventionally processed, and analyses were performed at 24 h PM except residual hemoglobin for which the samples were frozen (-80 degrees C) until analyses ( < 2 mo). There were no significant differences in pH or b* values at 24 h PM among any of the treatments. L* values were significantly higher, indicating lighter fillets in the ES and decapitated birds compared with the darker fillets from the CO(2) stunned and bled birds. The CO(2) slaughter and not bled birds had significantly higher a* values, indicating more red color, when compared with the ES and bled and decapitated birds. There were no significant differences in the residual hemoglobin contents in the broiler breast muscle when comparing all of the treatments except CO(2) slaughter and not bled, which was significantly (around 15%) greater. Overall TBA-reactive substances (TBARS; raw, cooked at 24 h, and cooked at 72 h PM) indicated that ES and bled birds had the lowest TBARS when compared with the remaining treatments. Consumer panels detected increased aroma (chicken meaty and warmed-over aromas) and flavor (chicken meaty and warmed-over flavors) in not bled samples at 24 h PM. By 72 h PM, however, there were no significant differences in aroma or flavor. Therefore, different slaughter and bleeding method may affect color and sensory properties of the broiler breast fillets, and the ES and decapitation method had the most favorable results for sensory quality.", "title": "The effect of blood removal on oxidation and shelf life of broiler breast meat." }, { "docid": "MED-1935", "text": "Recent evidences have highlighted an influence of micronutrients in the maintenance of telomere length (TL). In order to explore whether diet-related telomere shortening had any physiological relevance and was accompanied by significant damage in the genome, in the present study, TL was assessed by terminal restriction fragment (TRF) analysis in peripheral blood lymphocytes of 56 healthy subjects for which detailed information on dietary habits was available and data were compared \\with the incidence of nucleoplasmic bridges (NPBs), a marker of chromosomal instability related to telomere dysfunction visualised with the cytokinesis-blocked micronucleus assay. To increase the capability to detect even slight impairment of telomere function, the incidence of NPBs was also evaluated on cells exposed in vitro to ionising radiation. Care was taken to control for potential confounding factors that might influence TL, viz. age, hTERT genotype and smoking status. Data showed that higher consumption of vegetables was related with significantly higher mean TL (P = 0.013); in particular, the analysis of the association between micronutrients and mean TL highlighted a significant role of antioxidant intake, especially beta-carotene, on telomere maintenance (P = 0.004). However, the diet-related telomere shortening did not result in associated increased spontaneous or radiation-induced NPBs. The distribution of TRFs was also analysed and a slight prevalence of radiation-induced NPBs (P = 0.03) was observed in subjects with higher amount of very short TRFs (<2 kb). The relative incidence of very short TRFs was positively associate with ageing (P = 0.008) but unrelated to vegetables consumption and daily intake of micronutrients, suggesting that the degree of telomere erosion related with low dietary intake of antioxidants observed in this study was not so extensive to lead to chromosome instability.", "title": "Diet-related telomere shortening and chromosome stability" }, { "docid": "MED-4510", "text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.", "title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials" }, { "docid": "MED-2703", "text": "Extensive experimental data have revealed a central role for oxidative stress in atherogenesis and suggested a potential role for 'antioxidant' treatment in cardiovascular disease (CVD) [1-11]. Experimental data, however, have not translated into clinical benefit: most antioxidant vitamin trials have failed to reduce cardiovascular morbidity and mortality [12]. Moreover, recent clinical trials have suggested that mono-therapy with certain antioxidant vitamins like vitamin E may, in fact, be detrimental [13]. As a result of the disappointing outcome of 'antioxidant' vitamin trials, some authors have questioned both the utility of 'antioxidant' treatment in CVD and the supposedly central role of oxidative stress in atherogenesis [14-19]. Other investigators, however, sustain that the beneficial effects of lipid lowering and anti-hypertensive treatment are at least, in part, due to their 'antioxidant' properties, in addition to their specific pharmacological properties [20, 21]. Oxidant stress plays a pivotal role in atherogenesis, however, the clinical promise of antioxidant vitamins has failed to translate into clinical benefit. Increasing evidence suggests that more rigorous clinical trial designs are necessary to effectively divulge antioxidant utility and that a multifaceted antioxidant approach to atherosclerosis may yield the most clinical reward. This article reviews currently available evidence on the role of oxidant stress in atherosclerosis, analyzes the results of large anti-oxidant trials, and suggests ways to investigate the true role of antioxidant treatment in the clinical setting.", "title": "Atherosclerosis and oxidant stress: the end of the road for antioxidant vitamin treatment?" }, { "docid": "MED-2506", "text": "Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.", "title": "Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor..." }, { "docid": "MED-1254", "text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.", "title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation." }, { "docid": "MED-3729", "text": "Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Role of antioxidants in cancer therapy." }, { "docid": "MED-4509", "text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.", "title": "A meta-analysis of the effect of soy protein supplementation on serum lipids." }, { "docid": "MED-2504", "text": "It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways.", "title": "Nutrient control of TORC1, a cell-cycle regulator." }, { "docid": "MED-3127", "text": "AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. METHODS: A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. RESULTS: The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.", "title": "Study on soy isoflavone consumption and risk of breast cancer and survival." }, { "docid": "MED-1618", "text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.", "title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..." }, { "docid": "MED-2434", "text": "The specific role of dietary fat in breast cancer progression is unclear, although a low-fat diet was associated with decreased recurrence of estrogen receptor alpha negative (ER(-)) breast cancer. ER(-) basal-like MDA-MB-231 and MDA-MB-436 breast cancer cell lines contained a greater number of cytoplasmic lipid droplets compared to luminal ER(+) MCF-7 cells. Therefore, we studied lipid storage functions in these cells. Both triacylglycerol and cholesteryl ester (CE) concentrations were higher in the ER(-) cells, but the ability to synthesize CE distinguished the two types of breast cancer cells. Higher baseline, oleic acid- and LDL-stimulated CE concentrations were found in ER(-) compared to ER(+) cells. The differences corresponded to greater mRNA and protein levels of acyl-CoA:cholesterol acyltransferase 1 (ACAT1), higher ACAT activity, higher caveolin-1 protein levels, greater LDL uptake, and lower de novo cholesterol synthesis in ER(-) cells. Human LDL stimulated proliferation of ER(-) MDA-MB-231 cells, but had little effect on proliferation of ER(+) MCF-7 cells. The functional significance of these findings was demonstrated by the observation that the ACAT inhibitor CP-113,818 reduced proliferation of breast cancer cells, and specifically reduced LDL-induced proliferation of ER(-) cells. Taken together, our studies show that a greater ability to take up, store and utilize exogenous cholesterol confers a proliferative advantage to basal-like ER(-) breast cancer cells. Differences in lipid uptake and storage capability may at least partially explain the differential effect of a low-fat diet on human breast cancer recurrence.", "title": "High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation." }, { "docid": "MED-5114", "text": "Most of the early studies published on soy and breast cancer were not designed to test the effect of soy; the assessment of soy intake was usually crude and few potential confounders were considered in the analysis. In this review, we focused on studies with relatively complete assessment of dietary soy exposure in the targeted populations and appropriate consideration for potential confounders in the statistical analysis of study data. Meta-analysis of the 8 (1 cohort, 7 case–control) studies conducted in high-soy-consuming Asians show a significant trend of decreasing risk with increasing soy food intake. Compared to the lowest level of soy food intake (⩽5 mg isoflavones per day), risk was intermediate (OR=0.88, 95% confidence interval (CI)=0.78–0.98) among those with modest (∼10 mg isoflavones per day) intake and lowest (OR=0.71, 95% CI=0.60–0.85) among those with high intake (⩾20 mg isoflavones per day). In contrast, soy intake was unrelated to breast cancer risk in studies conducted in the 11 low-soy-consuming Western populations whose average highest and lowest soy isoflavone intake levels were around 0.8 and 0.15 mg per day, respectively. Thus, the evidence to date, based largely on case–control studies, suggest that soy food intake in the amount consumed in Asian populations may have protective effects against breast cancer.", "title": "Epidemiology of soy exposures and breast cancer risk" }, { "docid": "MED-1610", "text": "The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite." }, { "docid": "MED-4034", "text": "OBJECTIVES: To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men. DESIGN: Prospective, observational study. SETTING: Greater Boston, Massachusetts, metropolitan area. PARTICIPANTS: Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study. MEASUREMENTS: Dental and physical examinations were conducted every 3 to 5 years. Diet was assessed using food frequency questionnaires (FFQs). Mean follow-up was 15 years (range: 2-24 years). Periodontal disease progression on each tooth was defined as alveolar bone loss (ABL) advancement of 40% or more, probing pocket depth (PPD) of 2 mm or more, or tooth loss. Good and excellent fiber sources provided 2.5 g or more of fiber per serving. Multivariate proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of periodontal disease progression and tooth loss in relation to fiber sources, stratified according to age younger than 65 versus 65 and older, and controlled for smoking, body mass index, calculus, baseline periodontal disease level, caries, education, exercise, carotene, thiamin and caffeine intake, and tooth brushing. RESULTS: In men aged 65 and older, each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression (HR = 0.76, 95% CI = 0.60-0.95) and tooth loss (HR = 0.72, 95% CI = 0.53-0.97). Of the different food groups, only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL (HR = 0.86 per serving, 95% CI = 0.78-0.95), PPD (HR = 0.95, 95% CI = 0.91-0.99), and tooth loss (HR = 0.88, 95% CI = 0.78-0.99). No significant associations were seen in men younger than 65. CONCLUSION: Benefits of higher intake of high-fiber foods, especially fruits, on slowing periodontal disease progression are most evident in men aged 65 and older. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.", "title": "High-fiber foods reduce periodontal disease progression in men aged 65 and older: the Veterans Affairs normative aging study/Dental Longitudinal St..." }, { "docid": "MED-2216", "text": "BACKGROUND: Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD. OBJECTIVE: This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible. METHODS: This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data. RESULTS: For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan. CONCLUSION: Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.", "title": "Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries." }, { "docid": "MED-3149", "text": "Many health conditions are treated, at least in part, by therapeutic diets. Although the success of any intervention depends on its acceptability to the patient, the acceptability of therapeutic diets and factors that influence it have been largely neglected in nutrition research. A working definition of acceptability is proposed and an examination and summary are provided of available data on the acceptability of common diet regimens used for medical conditions. The goal is to suggest ways to improve the success of therapeutic diets. The proposed working definition of \"acceptability\" refers to the user's judgment of the advantages and disadvantages of a therapeutic diet-in relation to palatability, costs, and effects on eating behaviour and health-that influence the likelihood of adherence. Very low-calorie, reduced-fat omnivorous, vegetarian and vegan, and low-carbohydrate diets all achieve acceptability among the majority of users in studies of up to one year, in terms of attrition and adherence rates and results of questionnaires assessing eating behaviours. Longer studies are fewer, but they suggest that vegetarian, vegan, and reduced-fat diets are acceptable, as indicated by sustained changes in nutrient intake. Few studies of this length have been published for very low-calorie or low-carbohydrate diets. Long-term studies of adherence and acceptability of these and other therapeutic diets are warranted.", "title": "Four therapeutic diets: adherence and acceptability." }, { "docid": "MED-2372", "text": "BACKGROUND: Because of egg cholesterol content, reduction in egg consumption is generally recommended to reduce risk of cardiovascular disease. Recently, however, evidence has been accumulating to suggest that dietary cholesterol is less relevant to cardiovascular risk than dietary saturated fat. This randomized controlled crossover trial was conducted to determine the effects of egg ingestion on endothelial function, a reliable index of cardiovascular risk. METHODS: Forty-nine healthy adults (mean age 56 years, 40% females) underwent a baseline brachial artery reactivity study (BARS), and were assigned to two eggs or oats daily for 6 weeks in random sequence with a 4-week washout. A BARS was done at the end of each treatment phase, measuring flow-mediated vasodilation (FMD) in the brachial artery using a high-frequency ultrasound. RESULTS: FMD was stable in both egg and oat groups, and between-treatment differences were not significant (egg -0.96%, oatmeal -0.79%; p value >0.05). Six weeks of egg ingestion had no effect on total cholesterol (baseline: 203.8 mg/dl; post-treatment: 205.3) or LDL (baseline: 124.8 mg/dl; post-treatment: 129.1). In contrast, 6 weeks of oats lowered total cholesterol (to 194 mg/dl; p = 0.0017) and LDL (to 116.6 mg/dl; p = 0.012). There were no differences in body mass index (BMI), triglyceride, HDL or SBP levels between egg and oat treatment assignments. CONCLUSION: Short-term egg consumption does not adversely affect endothelial function in healthy adults, supporting the view that dietary cholesterol may be less detrimental to cardiovascular health than previously thought.", "title": "Egg consumption and endothelial function: a randomized controlled crossover trial." }, { "docid": "MED-3254", "text": "We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.", "title": "Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study." }, { "docid": "MED-2380", "text": "BACKGROUND AND AIMS: High blood pressure (BP) is considered a major risk factor for cardiovascular disease. Among lifestyle factors, diet plays a key role in the prevention and control of high BP. Therefore, it is important to elucidate which dietary components can exert beneficial effects on BP through modulation of endothelial function (EF) or by other mechanisms. In this paper we review the role of nutrients, foods, particularly nuts, and dietary patterns on BP control. DATA SYNTHESIS: Because nuts are low in sodium and contain significant amounts of mono- and polyunsaturated fatty acids, fiber, minerals such as magnesium, potassium and calcium, and antioxidants, they have been suggested as potentially protective foods against hypertension. Limited evidence from prospective studies and clinical trials suggests that nut consumption has a beneficial effect on both BP and EF. However, BP changes were a secondary outcome in nut feeding trials and no study used ambulatory BP monitoring as the standard for BP measurements. CONCLUSIONS: Further clinical trials, ideally using ambulatory BP monitoring, are needed to establish the potential protective effect of nut consumption on hypertension and vascular reactivity. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Nuts, hypertension and endothelial function." }, { "docid": "MED-4676", "text": "A widespread misconception has been developing among the Canadian public and among physicians. It is increasingly believed that consumption of dietary cholesterol and egg yolks is harmless. There are good reasons for long-standing recommendations that dietary cholesterol should be limited to less than 200 mg/day; a single large egg yolk contains approximately 275 mg of cholesterol (more than a day’s worth of cholesterol). Although some studies showed no harm from consumption of eggs in healthy people, this outcome may have been due to lack of power to detect clinically relevant increases in a low-risk population. Moreover, the same studies showed that among participants who became diabetic during observation, consumption of one egg a day doubled their risk compared with less than one egg a week. Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries. Patients at risk of cardiovascular disease should limit their intake of cholesterol. Stopping the consumption of egg yolks after a stroke or myocardial infarction would be like quitting smoking after a diagnosis of lung cancer: a necessary action, but late. The evidence presented in the current review suggests that the widespread perception among the public and health care professionals that dietary cholesterol is benign is misplaced, and that improved education is needed to correct this misconception. Résumé Une idée fausse et généralisée se répand au sein du public canadien et des médecins, qui pensent de plus en plus que la consommation de cholestérol alimentaire et de jaunes d’œuf est inoffensive. Les recommandations de longue date qui préconisent de limiter le cholestérol alimentaire à moins de 200 mg/jour reposent sur de bonnes raisons. Un seul gros jaune d’œuf contient environ 275 mg de cholestérol (plus que la portion quotidienne de cholestérol). Même si certaines études ont démontré que la consommation d’œufs n’est pas nuisible chez les personnes en santé, ce résultat peut découler de l’absence de capacité à déceler des augmentations pertinentes sur le plan clinique au sein d’une population à faible risque. De plus, les mêmes études ont révélé que chez les participants devenus diabétiques pendant la période d’observation, la consommation d’un œuf par jour doublait leur risque par rapport à la consommation de moins d’un œuf par semaine. Le régime ne vise pas à éviter le cholestérol, mais surtout les effets postprandiaux du cholestérol, des gras saturés, du stress oxydant et de l’inflammation. Le fait de se concentrer à tort sur les lipides à jeun occulte trois enjeux. Le cholestérol alimentaire accroît la susceptibilité des lipoprotéines à faible densité à l’oxydation, accroît la lipémie postprandiale et potentialise les effets secondaires des graisses saturées alimentaires. Le cholestérol alimentaire, y compris les jaunes d’œuf, est nuisible pour les artères. Les patients vulnérables aux maladies cardiovasculaires devraient limiter leur consommation de cholestérol. Le fait d’arrêter de consommer des jaunes d’œuf après un accident vasculaire cérébral ou un infarctus du myocarde s’apparenterait à arrêter de fumer après un diagnostic de cancer du poumon : c’est un geste nécessaire, mais entrepris tardivement. D’après les données probantes présentées dans la présente analyse, la perception généralisée du public et des professionnels de la santé selon laquelle le cholestérol alimentaire est un mal bénin est une idée fausse, et une meilleure information s’impose pour la corriger.", "title": "Dietary cholesterol and egg yolks: Not for patients at risk of vascular disease" }, { "docid": "MED-3135", "text": "Background: Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known. Methods: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1. Results: Although the overall frequency of CpG island promoter methylation events increased with age (P < 0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P = 0.051), INK4a/ARF (P = 0.042), HIN-1 (P = 0.044), and PRA (P = 0.032), as well as the overall frequency of methylation events (P = 0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had ≤4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters. Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.", "title": "CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis" }, { "docid": "MED-4559", "text": "The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.", "title": "Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?" }, { "docid": "MED-3908", "text": "BACKGROUND: Evidence suggests that consumption of apple or its bioactive components modulate lipid metabolism and reduce the production of proinflammatory molecules. However, there is a paucity of such research in human beings. OBJECTIVE: Women experience a lower rate of cardiovascular disease before menopause compared with men. However, after the onset of menopause, the risk of cardiovascular disease increases drastically due to ovarian hormone deficiency. Hence, we conducted a 1-year clinical trial to evaluate the effect of dried apple vs dried plum consumption in reducing cardiovascular disease risk factors in postmenopausal women. DESIGN: One-hundred sixty qualified postmenopausal women were recruited from the greater Tallahassee, FL, area during 2007-2009 and were randomly assigned to one of two groups: dried apple (75 g/day) or dried plum (comparative control). Fasting blood samples were collected at baseline, 3, 6, and 12 months to measure various parameters. Physical activity recall and 7-day dietary recall were also obtained. RESULTS: Neither of the dried fruit regimens significantly affected the participants' reported total energy intake throughout the study period. On the contrary, women who consumed dried apple lost 1.5 kg body weight by the end of the study, albeit not significantly different from the dried plum group. In terms of cholesterol, serum total cholesterol levels were significantly lower in the dried apple group compared with the dried plum group only at 6 months. Although dried plum consumption did not significantly reduce serum total cholesterol and low-density lipoprotein cholesterol levels, it lowered their levels numerically by 3.5% and 8%, respectively, at 12 months compared with baseline. This may explain the lack of significance observed between the groups. However, within the group, women who consumed dried apple had significantly lower serum levels of total cholesterol and low-density lipoprotein cholesterol by 9% and 16%, respectively, at 3 months compared with baseline. These serum values were further decreased to 13% and 24%, respectively, after 6 months but stayed constant thereafter. The within-group analysis also reported that daily apple consumption profoundly improved atherogenic risk ratios, whereas there were no significant changes in lipid profile or atherogenic risk ratios as a result of dried plum consumption. Both dried fruits were able to lower serum levels of lipid hydroperoxide and C-reactive protein. However, serum C-reactive protein levels were significantly lower in the dried plum group compared with the dried apple group at 3 months. CONCLUSIONS: There were no significant differences between the dried apple and dried plum groups in altering serum levels of atherogenic cholesterols except total cholesterol at 6 months. However, when within treatment group comparisons are made, consumption of 75 g dried apple (about two medium-sized apples) can significantly lower atherogenic cholesterol levels as early as 3 months. Furthermore, consumption of dried apple and dried plum are beneficial to human health in terms of anti-inflammatory and antioxidative properties. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.", "title": "Daily apple versus dried plum: impact on cardiovascular disease risk factors in postmenopausal women." }, { "docid": "MED-1552", "text": "OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.", "title": "Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies." }, { "docid": "MED-2530", "text": "Our understanding of coronary artery disease risk and the atherosclerotic process has changed greatly in recent years. For example, it is now known that angiographically apparent coronary artery plaque is not the major cause of myocardial infarction (MI). Rather, it is unstable, soft plaque that cannot be seen angiographically that is prone to rupture and result in infarction. Also important are changes in vascular reactivity resulting from diet. Cholesterol levels by themselves reveal little about a patient's coronary artery disease risk. Most infarctions occur in patients who have normal total cholesterol levels. At-risk patients can be identified using the ratio of total-to-high-density lipoprotein (HDL) cholesterol levels. The ratio of triglyceride to HDL cholesterol levels is also important. Simple steps to assess patients' risk in practice are outlined. Primary prevention trials demonstrate that coronary artery disease risk can be lowered dramatically with diet and drug therapy.", "title": "The new pathophysiology of coronary artery disease." }, { "docid": "MED-1613", "text": "The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.", "title": "Taiwanese vegetarians have higher insulin sensitivity than omnivores." }, { "docid": "MED-4030", "text": "BACKGROUND: Oral health care professionals can play an important role in preventing oral cancer by performing oral mucosal examinations to detect pre-cancerous changes and by educating patients about oral cancer prevention strategies, including dietary approaches. CONCLUSIONS: Current evidence supports a diet high in fruits, vegetables and plant-based foods for prevention of oral cancer. Dietary supplements-including vitamins and minerals-have not been shown to be effective as substitutes for a diet high in fruits and vegetables. CLINICAL IMPLICATIONS: In addition to discussing tobacco and alcohol use with patients (and, if relevant, betel nut and gutka consumption), as well as the risk of sexual transmission of human papillo-mavirus, clinicians should provide dietary advice for the prevention of oral cancer as part of routine patient education practices.", "title": "Diet and prevention of oral cancer: strategies for clinical practice." }, { "docid": "MED-4247", "text": "In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.", "title": "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial." }, { "docid": "MED-2967", "text": "The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.", "title": "Atherogenesis: a postprandial phenomenon." }, { "docid": "MED-1614", "text": "AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.", "title": "Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores." }, { "docid": "MED-3433", "text": "OBJECTIVES: Our goal was to evaluate the association between erectile dysfunction (ED) and risk of cardiovascular disease (CVD) and all-cause mortality by conducting a meta-analysis of prospective cohort studies. BACKGROUND: Observational studies suggest an association between ED and the incidence of CVD. However, whether ED is an independent risk factor of CVD remains controversial. METHODS: The PubMed database was searched through January 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twelve prospective cohort studies involving 36,744 participants were included in the meta-analysis. The overall combined relative risks for men with ED compared with the reference group were 1.48 (95% confidence interval [CI]: 1.25 to 1.74) for CVD, 1.46 (95% CI: 1.31 to 1.63) for coronary heart disease, 1.35 (95% CI: 1.19 to 1.54) for stroke, and 1.19 (95% CI: 1.05 to 1.34) for all-cause mortality. Sensitivity analysis restricted to studies with control for conventional cardiovascular risk factors yielded similar results. No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that ED significantly increases the risk of CVD, coronary heart disease, stroke, and all-cause mortality, and the increase is probably independent of conventional cardiovascular risk factors. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies." }, { "docid": "MED-1250", "text": "The effect of plant and animal protein on blood lipid levels was investigated in eight healthy normolipidemic men aged 18 to 27 yr. All subjects were fed both plant and animal protein diets in a cross-over design. Each diet was consumed for a 21-day period. Proteins from commonly used plant sources made up the plant protein diet. Beef protein was substituted for 55% of the plant proteins in the animal protein diet. Fasting venous blood samples were collected at the beginning of the study and at 7-day intervals throughout the 42-day study. Serum was analyzed for total cholesterol and triglycerides. Plasma low-density and high-density lipoprotein cholesterol were determined. There were not any statistically significant differences in mean serum total cholesterol or mean plasma low-density lipoprotein cholesterol when subjects consumed the diets. Mean plasma high-density lipoprotein cholesterol levels were significantly (p less than 0.05) elevated at the end of the 21-day period when the animal protein diet was consumed (48 +/- 3 mg/dl) compared to the period when the plant protein diet was fed (42 +/- 2 mg/dl). Mean serum triglyceride values were significantly (p less than 0.05) increased at day 7 of the plant protein diet period (136 +/- 19 mg/dl) compared to the same time period when the animal protein diet was consumed (84 +/- 12 mg/dl). The results of the study indicated that the ingestion of a diet in which 55% of the protein was supplied by beef protein was not associated with a hypercholesterolemic effect in healthy normolipidemic young men.", "title": "A comparison of the effect of diets containing beef protein and plant proteins on blood lipids of healthy young men." }, { "docid": "MED-2437", "text": "BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.", "title": "Diet and breast cancer: understanding risks and benefits." }, { "docid": "MED-2472", "text": "Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.", "title": "Vegan regimen with reduced medication in the treatment of bronchial asthma." }, { "docid": "MED-1885", "text": "PURPOSE OF REVIEW: The perceived notion that dietary cholesterol is associated with increased risk for coronary heart disease (CHD) has led to dietary recommendations of no more than 300 mg/day for healthy populations in the USA. This study will review the recent evidence that challenges the current dietary restrictions regarding cholesterol while it presents some beneficial effects of eggs (an icon for dietary cholesterol) in healthy individuals. RECENT FINDINGS: The European countries, Australia, Canada, New Zealand, Korea and India among others do not have an upper limit for cholesterol intake in their dietary guidelines. Further, existing epidemiological data have clearly demonstrated that dietary cholesterol is not correlated with increased risk for CHD. Although numerous clinical studies have shown that dietary cholesterol challenges may increase plasma LDL cholesterol in certain individuals, who are more sensitive to dietary cholesterol (about one-quarter of the population), HDL cholesterol also rises resulting in the maintenance of the LDL/HDL cholesterol ratio, a key marker of CHD risk. SUMMARY: The lines of evidence coming from current epidemiological studies and from clinical interventions utilizing different types of cholesterol challenges support the notion that the recommendations limiting dietary cholesterol should be reconsidered.", "title": "Rethinking dietary cholesterol." }, { "docid": "MED-4300", "text": "BACKGROUND AND AIMS: Nuts have been part of the human diet since prehistoric times. The aim of the present article is to describe the most important historical and cultural aspects of nut consumption throughout history. DATA SYNTHESIS: We discuss the following historical aspects of nuts originating in the Mediterranean: prehistory, the Egyptian civilization, their spread through the Mediterranean region by the Greek, Phoenician and Roman civilizations, and their reintroduction into Europe by means of the Al-Andalus culture. Particular emphasis is placed on the healthy and nutritional attributes that nuts have had throughout history. We also consider the role of the first globalization of food--the exchange of nuts between continents--and discuss the symbolism that nuts have had for humans throughout history in the context of cultural aspects of the Mediterranean region. CONCLUSIONS: Nuts and fruits are probably the earliest foods consumed by humans and are considered to be important because of their nutritional properties. Nuts have also been used in the past by different civilizations as drugs to prevent or treat several diseases. Copyright © 2010 Elsevier B.V. All rights reserved.", "title": "Cultural and historical aspects of Mediterranean nuts with emphasis on their attributed healthy and nutritional properties." }, { "docid": "MED-2596", "text": "BACKGROUND Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. METHODS We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses’ Health Study (1980–2010) and 42,498 men in the Health Professionals Follow-up Study (1986–2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. RESULTS During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. CONCLUSIONS In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. (Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation.)", "title": "Association of Nut Consumption with Total and Cause-Specific Mortality" }, { "docid": "MED-2512", "text": "Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.", "title": "Extending healthy ageing: nutrient sensitive pathway and centenarian population" }, { "docid": "MED-2886", "text": "PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.", "title": "Goji berry effects on macular characteristics and plasma antioxidant levels." }, { "docid": "MED-4878", "text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.", "title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)" }, { "docid": "MED-3787", "text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.", "title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma" }, { "docid": "MED-2889", "text": "Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Cataract is a self-defence reaction to protect the retina from oxidative damage." }, { "docid": "MED-5303", "text": "IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.", "title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors." }, { "docid": "MED-3200", "text": "In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.", "title": "Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study" }, { "docid": "MED-2501", "text": "Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Amino acid sensing and regulation of mTORC1." }, { "docid": "MED-2213", "text": "CONTEXT: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced. OBJECTIVE: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations. DESIGN: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance. SETTING AND PARTICIPANTS: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively. MAIN OUTCOME MEASURES: Incident cases of dementia and AD in each of the 2 populations. RESULTS: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]). CONCLUSION: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.", "title": "Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, I..." }, { "docid": "MED-5113", "text": "OBJECTIVE: This study investigated the effects of a soy-based low-calorie diet on weight control, body composition, and blood lipid profiles compared with a traditional low-calorie diet. METHODS: Thirty obese adults (mean body mass index 29-30 kg/m(2)) were randomized to two groups. The soy-based low-calorie group consumed soy protein as the only protein source, and the traditional low-calorie group consumed two-thirds animal protein and the rest plant protein in a 1200 kcal/d diet for 8 wk. A diet record was kept everyday throughout the study. Food intake was analyzed before and after the study. Anthropometric data were acquired every week, and biochemical data from before and after the 8-wk experiment were compared. RESULTS: Body weight, body mass index, body fat percentage, and waist circumference significantly decreased in both groups (P < 0.05). The decrease in body fat percentage in the soy group (2.2%, 95% confidence interval 1.6-2.8) was greater than that in the traditional group (1.4%, 95% confidence interval -0.1 to 2.8). Serum total cholesterol concentrations, low-density lipoprotein cholesterol concentrations, and liver function parameters decreased in the soy-based group and were significantly different from measurements in the traditional group (P < 0.05). No significant change in serum triacylglycerol levels, serum high-density lipoprotein cholesterol levels, and fasting glucose levels was found in the soy or traditional group. CONCLUSION: Soy-based low-calorie diets significantly decreased serum total cholesterol and low-density lipoprotein cholesterol concentrations and had a greater effect on reducing body fat percentage than traditional low-calorie diets. Thus, soy-based diets have health benefits in reducing weight and blood lipids.", "title": "Effectiveness of a soy-based compared with a traditional low-calorie diet on weight loss and lipid levels in overweight adults." }, { "docid": "MED-2589", "text": "BACKGROUND: Determination of the effects of dietary modification and hyperlipidemic medications in the elderly (> sixty-five years of age) patient has not been significantly investigated to date despite knowledge that elevated cholesterol (TC) and triglyceride (TG) levels increase the risk of coronary artery disease (CAD). METHODS: Twenty-seven individuals were placed into one of three treatment groups and longitudinally followed up to examine the effects of diet and hyperlipidemic medications on TC and TG levels. Group 1 (n = 14) received neither dietary nor drug therapy. Group 2 (n = 9) received dietary counseling without concomitant hyperlipidemic medications. Subjects in group 3 (n = 4) underwent dietary instruction for six months and hyperlipidemic medication(s) for eighteen months. RESULTS: Subjects in group 1 demonstrated a statistical increase in TC (P < or = 0.001) during the study. Patients in groups 2 (P < or = 0.001) and 3 (P < or = 0.05) demonstrated statistical improvement in TC reduction during dietary counseling. The effect on TC was blunted in group 3 after dietary counseling was discontinued. Reductions in TG levels were significant (P < or = 0.001) only for patients in group 2. CONCLUSION: Elderly individuals were able to significantly reduce both TC and TG levels by dietary modification alone. Minimal improvement was seen with the addition of hyperlipidemic medications.", "title": "Treating hyperlipidemia in the elderly." }, { "docid": "MED-2893", "text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.", "title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis." }, { "docid": "MED-4832", "text": "Cardiovascular disease (CVD) is the most important adult health problem in the world. Epidemiological studies and laboratory experiments have shown that fruit and vegetable consumption has protective effects against CVD. The purpose of the study was to investigate the effects of consumption of two kiwifruit per day on the lipid profile, antioxidants and markers of lipid peroxidation in hyperlipidemic adult men and women in Taiwan. Forty-three subjects who had hyperlipidemia, including 13 males and 30 females, participated in this study. They were asked to consume two kiwifruit per day for 8 weeks. Anthropometric measurements were made. Before the intervention and at 4 and 8 weeks of the intervention, fasting blood samples were analyzed for total cholesterol, triacylglycerol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol (HDL-C). Additionally vitamin E and vitamin C, the malondialdehyde + 4-hydroxy-2(E)-nonenal concentration, and the lag time of LDL oxidation were determined. No significant differences from baseline to 8 weeks of the intervention were detected for triacylglycerol, total cholesterol, or LDL cholesterol. However, after 8 weeks of consumption of kiwifruit, the HDL-C concentration was significantly increased and the LDL cholesterol/HDL-C ratio and total cholesterol/HDL-C ratio were significantly decreased. Vitamin C and vitamin E also increased significantly. In addition, the lag time of LDL oxidation and malondialdehyde + 4-hydroxy-2(E)-nonenal had significantly changed at 4 and 8 weeks during the kiwifruit intervention. Regular consumption of kiwifruit might exert beneficial effects on the antioxidative status and the risk factors for CVD in hyperlipidemic subjects.", "title": "Effects of kiwifruit consumption on serum lipid profiles and antioxidative status in hyperlipidemic subjects." }, { "docid": "MED-2507", "text": "Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \"weak\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \"weak\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ..." }, { "docid": "MED-2509", "text": "DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.", "title": "Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR" }, { "docid": "MED-1914", "text": "How can adverse experiences in early life, such as maltreatment, exert such powerful negative effects on health decades later? The answer may lie in changes to DNA. New research suggests that exposure to stress can accelerate the erosion of DNA segments called telomeres. Shorter telomere length correlates with chronological age and also disease morbidity and mortality. Thus, telomere erosion is a potential mechanism linking childhood stress to health problems later in life. However, an array of mechanistic, methodological, and basic biological questions must be addressed in order to translate telomere discoveries into clinical applications for monitoring health and predicting disease risk. This paper covers the current state of the science and lays out new research directions.", "title": "Early life stress and telomere length: Investigating the connection and possible mechanisms" }, { "docid": "MED-3247", "text": "Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY", "title": "Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis" }, { "docid": "MED-4715", "text": "The present pilot study analyzed, for the first time, the in vivo effect of Medjool or Hallawi date consumption by healthy subjects on serum glucose, lipids, and oxidative stress. Total phenolics concentration in the Hallawi versus Medjool dates was greater by 20-31%. The major proportion of the soluble phenolics in both date varieties consisted of phenolic acids, mainly ferulic acid and coumaric acid derivatives, and also chlorogenic and caffeic acid derivatives. Unlike the Medjool dates, Hallawi dates contained a significant proportion of catechins as well. In addition, both varieties contained a quercetin derivative. Both date varieties possess antioxidative properties in vitro, but the ferric ion reducing antioxidant power of Hallawi versus Medjool dates was higher by 24%. Ten healthy subjects consumed, for a period of 4 weeks 100 g/day of either Medjool or Hallawi dates. The date consumption did not significantly affect the subjects' body mass index (BMI), their serum total cholesterol, or their cholesterol levels in the VLDL, LDL, or HDL fractions. Most important, fasting serum glucose and triacylglycerol levels were not increased after consumption of either date variety, and serum triacylglycerol levels even significantly (p < 0.05) decreased, by 8 or 15% after Medjool or Hallawi date consumption, respectively. Basal serum oxidative status was significantly (p < 0.01) decreased by 33%, as compared to the levels observed before consumption, after Hallawi (but not Medjool) date consumption. Similarly, the susceptibility of serum to AAPH-induced lipid peroxidation decreased by 12%, but only after Hallawi date consumption. In agreement with the above results, serum activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) significantly increased, by 8%, after Hallawi date consumption. It is concluded that date consumption (and mainly the Hallawi variety) by healthy subjects, despite their high sugar content, demonstrates beneficial effects on serum triacylglycerol and oxidative stress and does not worsen serum glucose and lipid/lipoprotein patterns, and thus can be considered an antiatherogenic nutrient .", "title": "Effects of date ( Phoenix dactylifera L., Medjool or Hallawi Variety) consumption by healthy subjects on serum glucose and lipid levels and on seru..." }, { "docid": "MED-3204", "text": "Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.", "title": "Management of grapefruit-drug interactions." }, { "docid": "MED-3148", "text": "We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.", "title": "Sympathetic nervous system activity and resting metabolic rate in vegetarians." }, { "docid": "MED-2526", "text": "Investigators collected and analyzed mortality data for >50 diseases, including 7 different cancers, from 65 counties and 130 villages in rural mainland China. Blood, urine, food samples, and detailed dietary data were collected from 50 adults in each village and analyzed for a variety of nutritional, viral, hormonal, and toxic chemical factors. In rural China, fat intake was less than half that in the United States, and fiber intake was 3 times higher. Animal protein intake was very low, only about 10% of the US intake. Mean serum total cholesterol was 127 mg/dL in rural China versus 203 mg/dL for adults aged 20-74 years in the United States. Coronary artery disease mortality was 16.7-fold greater for US men and 5.6-fold greater for US women than for their Chinese counterparts. The combined coronary artery disease mortality rates for both genders in rural China were inversely associated with the frequency of intake of green vegetables and plasma erythrocyte monounsaturated fatty acids, but positively associated with a combined index of salt intake plus urinary sodium and plasma apolipoprotein B. These apolipoproteins, in turn, are positively associated with animal protein intake and the frequency of meat intake and inversely associated with plant protein, legume, and light-colored vegetable intake. Rates of other diseases were also correlated with dietary factors. There was no evidence of a threshold beyond which further benefits did not accrue with increasing proportions of plant-based foods in the diet.", "title": "Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study." }, { "docid": "MED-5072", "text": "Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.", "title": "Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept." }, { "docid": "MED-4029", "text": "We compared the effect on enamel demineralisation in situ of both whole and juiced fruits and vegetables. Volunteers wore removable mandibular appliances carrying pre-demineralised human enamel slabs and consumed one of the test foods 7 times a day for 10 days. The test foods were apples, oranges, grapes, carrots, and tomatoes, consumed either whole (sugars located intrinsically) or as a juice (extrinsic or free sugars). Raisins containing 64% sugars, but intrinsic by definition, were also studied. The mineral profile of the enamel slabs was studied before and after the test period using transverse microradiography and showed further demineralisation for all test foods, irrespective of the form of consumption. Significant demineralisation was also observed with raisins. No significant differences were found between the solid and juiced foods. In conclusion, sugars present intrinsically on consumption had a similar demineralising potential as free sugars and could not be considered less cariogenic. Copyright © 2011 S. Karger AG, Basel.", "title": "Comparison of the effects of whole and juiced fruits and vegetables on enamel demineralisation in situ." }, { "docid": "MED-1615", "text": "Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors." }, { "docid": "MED-4022", "text": "BACKGROUND: Erectile dysfunction (ED) and chronic periodontitis (CP) share common risk factors. There is only one report on the association between ED and CP. Thus, the aim of this study is to find the association between vasculogenic ED and CP. METHODS: A total of 70 patients (mean age: 35.3 ± 3.64 years) clinically diagnosed with ED were included in the study. They were given the Sexual Health Inventory for Men Questionnaire and subjected to colored penile Doppler ultrasound. Periodontal parameters of probing depth and periodontal attachment level were recorded. Five patients with ED and CP were selected randomly for cardiac color Doppler to assess the integrity. RESULTS: Among the selected vasculogenic patients with ED, mild-to-moderate vasculogenic ED showed the highest prevalence, whereas prevalence for CP among all vasculogenic patients with ED was highest among severe ED (81.8%). Association of CP and vasculogenic ED was found to be correlated positively, but it showed no statistical significance. Two of five patients were found to have vascular insufficiency. CONCLUSIONS: It can be hypothesized that an association exists between vasculogenic ED and CP in young males. However, a large-scale study with confounder analysis and a longitudinal follow-up is warranted.", "title": "Association between chronic periodontitis and vasculogenic erectile dysfunction." }, { "docid": "MED-3130", "text": "Although soy phytoestrogens have been postulated to exert a protective effect against breast cancer, the attendant mechanisms, in particular epigenetics underpinnings, have remained elusive. We investigated the putative effects on DNA methylation by two naturally occurring isoflavones, genistein and daidzein, in a study of the BRCA1 and BRCA2 oncosuppressor genes in breast cancer cell lines (MCF-7, MDA-MB 231, and MCF10a). A demethylant agent, the 5-azacytidine, and a methylant, the budesonide, were used as treatment controls. DNA methylation of BRCA1 and BRCA2 was investigated with methylated DNA immunoprecipitation coupled with PCR. In parallel, protein expression was determined by Western blot, immunohistochemistry, and confocal microscopy. Our results suggest that treatment with 18.5 μM Genistein or 78.5 μM Daidzein might reverse DNA hypermethylation and restore the expression of the oncosuppressor genes BRCA1 and BRCA2. 5-Azacitydine also enhanced the reexpression of these genes while budesonide had an opposite effect. To the best of our knowledge, these observations, while requiring replication, provide new evidence on potential epigenetic mechanisms by which genistein and daidzein might contribute to regulation of the BRCA1 and BRCA2. Future studies are warranted on whether the demethylating effect of genistein and daidzein is global or focused on select candidate genes.", "title": "Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer?" }, { "docid": "MED-2383", "text": "During the last decades, nuts have attracted the attention of researchers for their potential benefits in cardiovascular prevention. We discuss here some aspects of the assumed beneficial effects of nuts, weighing them against potential harm. Epidemiological observations and controlled intervention trials consistently suggest that nuts consumption is associated with improved serum lipid profile, thus helping decrease cardiovascular risk. Being nuts an energy dense food, their impact on energy balance and body weight should be considered. In particular, the claim that adding nuts to the habitual diet, thus increasing calorie intake, does not cause body fat accumulation still needs evidence and biological plausibility. The potential risk associated with the relatively frequent occurrence of allergic reactions following the consumption of nuts is also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "The role of nuts in the optimal diet: time for a critical appraisal?" }, { "docid": "MED-4025", "text": "Excessive consumption of acidic drinks and foods contributes to tooth erosion. The aims of the present in vitro study were twofold: (1) to assess the erosive potential of different dietary substances and medications; (2) to determine the chemical properties with an impact on the erosive potential. We selected sixty agents: soft drinks, an energy drink, sports drinks, alcoholic drinks, juice, fruit, mineral water, yogurt, tea, coffee, salad dressing and medications. The erosive potential of the tested agents was quantified as the changes in surface hardness (ΔSH) of enamel specimens within the first 2 min (ΔSH2-0 = SH2 min - SHbaseline) and the second 2 min exposure (ΔSH4-2 = SH4 min - SH2 min). To characterise these agents, various chemical properties, e.g. pH, concentrations of Ca, Pi and F, titratable acidity to pH 7·0 and buffering capacity at the original pH value (β), as well as degree of saturation (pK - pI) with respect to hydroxyapatite (HAP) and fluorapatite (FAP), were determined. Erosive challenge caused a statistically significant reduction in SH for all agents except for coffee, some medications and alcoholic drinks, and non-flavoured mineral waters, teas and yogurts (P < 0·01). By multiple linear regression analysis, 52 % of the variation in ΔSH after 2 min and 61 % after 4 min immersion were explained by pH, β and concentrations of F and Ca (P < 0·05). pH was the variable with the highest impact in multiple regression and bivariate correlation analyses. Furthermore, a high bivariate correlation was also obtained between (pK - pI)HAP, (pK - pI)FAP and ΔSH.", "title": "Analysis of the erosive effect of different dietary substances and medications." }, { "docid": "MED-4466", "text": "OBJECTIVE: To evaluate the effect of 3-month kale (Brassica oleracea acephala) juice supplementation on coronary artery disease risk factors among hypercholesterolemic men. METHODS: Thirty-two men with hypercholesterolemia (> 200 mg/dL) were recruited after annual health examinations among the faculty and staff at university. The subjects consumed 150 mL of kale juice per day for a 12-week intervention period. Dietary and anthropometric assessments were performed and blood samples were collected to evaluate biochemical profiles before and after supplementation. RESULTS: Serum concentrations of HDL-cholesterol, and HDL- to LDL-cholesterol ratio were significantly increased by 27% (P<0.0001) and 52% (P<0.0001), respectively. The LDL-cholesterol concentration and the atherogenic index were significantly reduced by 10% (P=0.0007) and 24.2% (P<0.0001), respectively without affecting body mass index, waist and hip circumferences, or nutrient intakes after three months of supplementation. While there was no difference in the concentration of malondialdehyde, significant increase in glutathione peroxidase activity (P=0.0005) were accompanied by a significant increase in the serum selenium level (P=0.0132). It was also found that the responses of these risk factors to kale juice administration were dependent on smoking status. CONCLUSION: Regular meals supplementation with kale juice can favorably influence serum lipid profiles and antioxidant systems, and hence contribute to reduce the risks of coronary artery disease in male subjects with hyperlipidemia.", "title": "Kale juice improves coronary artery disease risk factors in hypercholesterolemic men." }, { "docid": "MED-2079", "text": "Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk. Copyright © 2014 Elsevier Inc. All rights reserved.", "title": "One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans." }, { "docid": "MED-1889", "text": "Consumption of eggs for a long period was shown to result in hypercholesterolemia and is generally restricted for this reason. In the present study we analyzed the effect of eggs consumption for 3 weeks on lipoprotein atherogenicity. Consumption of 2 eggs per day with the meals, for 3 weeks resulted in a minor elevation in plasma glucose and urea concentrations. Plasma cholesterol concentration increased by 11% (p < 0.05) as a result of increased plasma low-density lipoprotein (LDL) cholesterol levels. Plasma triglycerides decreased by 13% (p < 0.01), but there were no significant alterations in plasma apolipoproteins A-I or B-100 concentrations. Plasma high-density lipoprotein (HDL) cholesterol decreased by 11% (p < 0.05). There was a 13% reduction, though not significant, in the cholesterol efflux from J-774 A.1 macrophages by HDL that was derived after eggs consumption in comparison to HDL that was obtained at baseline. The susceptibility of plasma [using 100 mM of 2,2' azobis 2-amidinopropane (AAPH)] as well as that of LDL (using 10 microM of copper ions) to lipid peroxidation was increased by 42% and 34%, respectively, as measured by the thiobarbituric acid reactive substance (TBARS) assay (p < 0.01). Kinetic analysis of LDL oxidation by copper ions revealed a 37% reduction in the lag time required for the initiation of LDL oxidation after 3 weeks of eggs consumption. The total plasma fatty acids concentration increased from 2.2 +/- 0.5 to 3.2 +/- 0.6 mg/ml. The plasma antioxidants, vitamin E and carotenoids were not significantly affected by eggs consumption. We conclude that eggs consumption, in addition to its hypercholesterolemic effect, increases plasma and LDL oxidizability, a phenomenon which was shown to enhance the progression of atherosclerosis. The atherogenic properties may contribute to the accelerated atherosclerosis prevalent in populations with high cholesterol intake.", "title": "Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation." }, { "docid": "MED-1924", "text": "Cellular senescence is an in vivo and in vitro phenomenon, accompanied by physiological changes including cessation of division and disturbances of organelle structure and function. Review of the literature was undertaken to determine whether there is evidence that whole organism aging and cell senescence share a common initiation pathway. In vivo aged cells of different lineages, including aged T lymphocytes, show high expression of the INK4A-p16 gene. In cell culture when telomeres are shortened past a key length or state, the Arf/Ink gene system (p16/p14 humans, p16/p19 mice) switches on and activates p53, which suppresses further cell division. The p53 gene is a key tumor suppressor and its deletion or mutation allows cancerous growth. The switching on of p53 also causes changes in fatty acid metabolism, especially down-regulation of both fatty acid synthase and stearoyl-CoA (delta-9) desaturase. The co-suppression of these genes together with enhanced uptake of extracellular fatty acids, leads to raised levels of cellular palmitate and induction of either apoptosis or senescence. In senescent cells, the fatty acid composition of the cellular membranes alters and leads to changes in both structure and function of organelles, especially mitochondria. Animal models of accelerated aging exhibit repression of stearoyl-CoA desaturase activity while anti-aging calorie restriction stimulates the same enzyme system. It is concluded that aging in cells and whole organisms share a common initiation pathway and that cellular senescence is protective against cancer. Healthy longevity is likely to be most enhanced by factors that actively suppress excessive cell division.", "title": "Saturated fatty acid metabolism is key link between cell division, cancer, and senescence in cellular and whole organism aging" }, { "docid": "MED-4837", "text": "BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.", "title": "Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal." }, { "docid": "MED-1429", "text": "The first four reviews in this series (Steinberg, D. 2004. J. Lipid Res. 45: 1583-1593; Steinberg, D. 2005. J. Lipid Res. 46: 179-190; Steinberg, D. 2005. J. Lipid Res. 46: 2037-2051; Steinberg, D. 2006. J. Lipid Res. 47: 1-14) traced the gradual accumulation of evidence, evidence of several different kinds, supporting the lipid hypothesis. They tracked the history from Anitschkow's 1913 classic work on the cholesterol-fed rabbit model to the breakthrough 1984 Coronary Primary Prevention Trial, the first large, randomized, double-blind primary intervention trial showing that decreasing blood cholesterol (using cholestyramine) significantly reduces coronary heart disease events. At that point, for the first time, decreasing blood cholesterol levels became an official national public health goal. Still, only a small fraction of patients at high risk were getting appropriate cholesterol-lowering treatment, and a number of important clinical questions remained unanswered. This final review in the series traces the early studies that led to the discovery of the statins and briefly reviews the now familiar large-scale clinical trials demonstrating their safety and their remarkable effectiveness in reducing coronary heart disease morbidity and mortality.", "title": "Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the s..." }, { "docid": "MED-2848", "text": "Type 1 diabetes is increasing rapidly in many parts of the Western world, most evidently in Scandinavia. A low concordance rate of insulin-dependent diabetes mellitus among monozygotic twins clearly indicates that genetic risk factors may be necessary, but are not sufficient for the disease to occur. The strongest genetic risk markers are located in the HLA region of chromosome 6, but these DNA specificities differ in different populations. Risk genes are indicated in other chromosomes of the human genome, suggesting a complex interaction between genes and environment as the cause of the disease. The pathogenesis of the disease is proposed to be autoimmune in nature and environmental risk factors may either initiate autoimmunity or accelerate an already ongoing beta-cell destruction. Risk factors disclosed by epidemiological studies that may accelerate the pathogenetic process are: a cold environment, a high growth rate, infections and stressful life events. Risk factors that may initiate the autoimmune process include early exposure to cow's milk proteins, nitrosamines or early foetal events such as blood group incompatibility or foetal viral infections. In conclusion, population-based epidemiological studies have helped to confirm proposed aetiological models that have arisen from experimental research. These epidemiological studies have also introduced important new findings that may reveal the complex aetiology of the disease and advance understanding closer to the ultimate goal of primary prevention.", "title": "The aetiology of type 1 diabetes: an epidemiological perspective." }, { "docid": "MED-2849", "text": "Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus. However, their association with gestational diabetes mellitus (GDM) has not been evaluated. The authors assessed such associations in both a prospective cohort study (1996–2008; 3,158 participants) and a case-control study (1998–2002; 185 cases, 411 controls). A food frequency questionnaire was used to assess maternal diet. Multivariable models were used to derive relative risks and 95% confidence intervals. Compared with no egg consumption, adjusted relative risks for GDM were 0.94, 1.01, 1.12, 1.54, and 2.52 for consumption of ≤1, 2–3, 4–6, 7–9, and ≥10 eggs/week, respectively (P for trend = 0.008). Women with high egg consumption (≥7/week) had a 1.77-fold increased risk compared with women with lower consumption (95% confidence interval (CI): 1.19, 2.63). The relative risk for the highest quartile of cholesterol intake (≥294 mg/day) versus the lowest (<151 mg/day) was 2.35 (95% CI: 1.35, 4.09). In the case-control study, the adjusted odds ratio for consuming ≥7 eggs/week versus <7 eggs/week was 2.65 (95% CI: 1.48, 4.72), and the odds of GDM increased with increasing cholesterol intake (P for trend = 0.021). In conclusion, high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM.", "title": "Risk of Gestational Diabetes Mellitus in Relation to Maternal Egg and Cholesterol Intake" }, { "docid": "MED-2527", "text": "BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.", "title": "Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients." }, { "docid": "MED-1428", "text": "The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals.", "title": "Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal." }, { "docid": "MED-1890", "text": "BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological s searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.", "title": "Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis." }, { "docid": "MED-3198", "text": "BACKGROUND: Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. OBJECTIVES: The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. DESIGN: The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. RESULTS: After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. CONCLUSION: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.", "title": "Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content." }, { "docid": "MED-2524", "text": "Following a heart-healthy diet to lower cholesterol levels is often assumed to be difficult, to be burdensome, and to have a negative impact on quality of life (QOL). The purpose of this study was to evaluate the impact of medical nutrition therapy (MNT) versus usual care (UC) for hypercholesterolemia on patient satisfaction and QOL. Ninety ambulatory care patients (60 men and 30 women), age 28 to 66, were randomly assigned to receive either MNT from dietitians using a National Cholesterol Education Program-based protocol or UC from their physicians. Patients who received MNT reported no difference in QOL related to the taste or enjoyment of food compared with UC patients. However, the MNT group reported initial improvements in QOL related to the convenience and cost of following a low-fat diet when compared with the UC group. The MNT group also reported significant and lasting improvements in perceived QOL related to self-care compared with the UC group. MNT patients were more satisfied with the interaction at visits, knowledge and ability to manage their cholesterol, eating habits, appearance, time spent exercising, and life in general. Moreover, MNT patients did not report any negative impact related to following a low-fat diet in regard to feeling restricted by diet; interference with lifestyle activities; or difficulty planning, purchasing, or preparing meals or eating away from home. Contrary to popular belief there is no apparent reduction but rather an improvement in some measures of QOL and patient satisfaction with MNT for hypercholesterolemia.", "title": "Medical nutrition therapy for hypercholesterolemia positively affects patient satisfaction and quality of life outcomes." }, { "docid": "MED-2588", "text": "Objective Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence. Data sources MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included. Review methods Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting. Results We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07–1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98–1.24) and 0.98 (0.78–1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results. Conclusion Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.", "title": "Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies" }, { "docid": "MED-1920", "text": "Overweight and obesity are major contributors to both type 2 diabetes and cardiovascular disease (CVD). Moreover, individuals with type 2 diabetes who are overweight or obese are at particularly high risk for CVD morbidity and mortality. Although short-term weight loss has been shown to ameliorate obesity-related metabolic abnormalities and CVD risk factors, the long-term consequences of intentional weight loss in overweight or obese individuals with type 2 diabetes have not been adequately examined. The primary objective of the Look AHEAD clinical trial is to assess the long-term effects (up to 11.5 years) of an intensive weight loss program delivered over 4 years in overweight and obese individuals with type 2 diabetes. Approximately 5000 male and female participants who have type 2 diabetes, are 45-74 years of age, and have a body mass index >or=25 kg/m(2) will be randomized to one of the two groups. The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. This program is compared to a control condition given diabetes support and education. The primary study outcome is time to incidence of a major CVD event. The study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between the two groups. Other outcomes include components of CVD risk, cost and cost-effectiveness, diabetes control and complications, hospitalizations, intervention processes, and quality of life.", "title": "Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in ..." }, { "docid": "MED-1801", "text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.", "title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein." }, { "docid": "MED-2179", "text": "OBJECTIVE: To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese. DESIGN: Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments. SETTING: Elderly Nutrition and Health Survey in Taiwan, 1999-2000. SUBJECTS: Nationally representative free-living elderly people aged ≥65 years (n 1888). RESULTS: During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings. CONCLUSIONS: Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.", "title": "Cooking frequency may enhance survival in Taiwanese elderly." }, { "docid": "MED-5115", "text": "The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus \"high\" doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of \"the dose defines the poison\" applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.", "title": "Genistein genotoxicity: critical considerations of in vitro exposure dose." }, { "docid": "MED-1619", "text": "BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.", "title": "No evidence of insulin resistance in normal weight vegetarians. A case control study." }, { "docid": "MED-3250", "text": "The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.", "title": "Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia." }, { "docid": "MED-3788", "text": "Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.", "title": "Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis" }, { "docid": "MED-3815", "text": "Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.", "title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes" }, { "docid": "MED-3207", "text": "Summary Grapefruit is a popular, tasty and nutritive fruit enjoyed globally. Biomedical evidence in the last 10 years has, however, shown that consumption of grapefruit or its juice is associated with drug interactions, which, in some cases, have been fatal. Grapefruit-induced drug interactions are unique in that the cytochrome P450 enzyme CYP3A4, which metabolises over 60% of commonly prescribed drugs as well as other drug transporter proteins such as P-glycoprotein and organic cation transporter proteins, which are all expressed in the intestines, are involved. However, the extent to which grapefruit–drug interactions impact on clinical settings has not been fully determined, probably because many cases are not reported. It has recently emerged that grapefruit, by virtue of its rich flavonoid content, is beneficial in the management of degenerative diseases such as diabetes and cardiovascular disorders. This potentially explosive subject is reviewed here.", "title": "The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives" }, { "docid": "MED-3396", "text": "OBJECTIVES: To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. METHODS: Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. RESULTS: A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. CONCLUSIONS: There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.", "title": "Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms." }, { "docid": "MED-4032", "text": "AIM: The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. METHODS: A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. RESULTS: The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. CONCLUSION: In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.", "title": "Oral implications of the vegan diet: observational study." }, { "docid": "MED-4301", "text": "BACKGROUND: Epidemiological studies have consistently associated nut consumption with reduced risk for coronary heart disease. Subsequently, many dietary intervention trials investigated the effects of nut consumption on blood lipid levels. The objectives of this study were to estimate the effects of nut consumption on blood lipid levels and to examine whether different factors modify the effects. METHODS: We pooled individual primary data from 25 nut consumption trials conducted in 7 countries among 583 men and women with normolipidemia and hypercholesterolemia who were not taking lipid-lowering medications. In a pooled analysis, we used mixed linear models to assess the effects of nut consumption and the potential interactions. RESULTS: With a mean daily consumption of 67 g of nuts, the following estimated mean reductions were achieved: total cholesterol concentration (10.9 mg/dL [5.1% change]), low-density lipoprotein cholesterol concentration (LDL-C) (10.2 mg/dL [7.4% change]), ratio of LDL-C to high-density lipoprotein cholesterol concentration (HDL-C) (0.22 [8.3% change]), and ratio of total cholesterol concentration to HDL-C (0.24 [5.6% change]) (P < .001 for all) (to convert all cholesterol concentrations to millimoles per liter, multiply by 0.0259). Triglyceride levels were reduced by 20.6 mg/dL (10.2%) in subjects with blood triglyceride levels of at least 150 mg/dL (P < .05) but not in those with lower levels (to convert triglyceride level to millimoles per liter, multiply by 0.0113). The effects of nut consumption were dose related, and different types of nuts had similar effects on blood lipid levels. The effects of nut consumption were significantly modified by LDL-C, body mass index, and diet type: the lipid-lowering effects of nut consumption were greatest among subjects with high baseline LDL-C and with low body mass index and among those consuming Western diets. CONCLUSION: Nut consumption improves blood lipid levels in a dose-related manner, particularly among subjects with higher LDL-C or with lower BMI.", "title": "Nut consumption and blood lipid levels: a pooled analysis of 25 intervention trials." }, { "docid": "MED-2436", "text": "The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients.", "title": "Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients." }, { "docid": "MED-3252", "text": "It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The molecular basis of nutritional intervention in multiple sclerosis: a narrative review." }, { "docid": "MED-2076", "text": "BACKGROUND: Berries are a particularly rich source of polyphenols. They also contain other bioactive substances, such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods (eg, cocoa, tea, and red wine) may induce beneficial changes in pathways related to cardiovascular health. Whether the consumption of berries has similar effects is unknown. OBJECTIVE: We aimed to investigate the effects of berry consumption on hemostatic function, serum lipids, and blood pressure (BP). DESIGN: Middle-aged unmedicated subjects (n = 72) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind, randomized, placebo-controlled intervention trial. RESULTS: Berry consumption inhibited platelet function as measured with a platelet function analyzer (using collagen and ADP as platelet activator) [changes: 11% and -1.4% in the berry and control groups, respectively; P = 0.018, analysis of covariance (ANCOVA)]. Plasma biomarkers of platelet activation, coagulation, and fibrinolysis did not change during the intervention. Serum HDL-cholesterol concentrations increased significantly more (P = 0.006, ANCOVA) in the berry than in the control group (5.2% and 0.6%, respectively), but total cholesterol and triacylglycerol remained unchanged. Systolic BP decreased significantly (P = 0.050, ANCOVA); the decrease mostly occurred in subjects with high baseline BP (7.3 mm Hg in highest tertile; P = 0.024, ANCOVA). Polyphenol and vitamin C concentrations in plasma increased, whereas other nutritional biomarkers (ie, folate, tocopherols, sodium, and potassium) were unaffected. CONCLUSION: The consumption of moderate amounts of berries resulted in favorable changes in platelet function, HDL cholesterol, and BP. The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease.", "title": "Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol." }, { "docid": "MED-2427", "text": "Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.", "title": "Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents" }, { "docid": "MED-2697", "text": "OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.", "title": "Impaired endothelial function following a meal rich in used cooking fat." }, { "docid": "MED-4833", "text": "Effective diets reduce blood lipids and oxidative damage, both of which have been linked to the complications of diabetes and coronary heart disease. Our objective was to assess the effect of adding strawberries, as a source of antioxidants, to improve the antioxidant effect of a cholesterol-lowering diet (dietary portfolio). To this end, 28 hyperlipidemic subjects who had followed the dietary portfolio consisting of soy, viscous fiber, plant sterol, and nuts for a mean of 2.5 years were randomized to receive supplements of strawberries (454 g/d, 112 kcal) or additional oat bran bread (65 g/d, 112 kcal, approximately 2 g beta-glucan) (control) in a randomized 1-month crossover study with a 2-week washout. Strawberry supplementation resulted in a greater reduction in oxidative damage to low-density lipoprotein (LDL) measured as thiobarbituric acid-reactive substances in the LDL fraction (P = .014). At the end of the strawberry period, reductions in LDL cholesterol and in the ratio of total to high-density lipoprotein cholesterol were maintained close to 1-year values at -13.4% +/- 2.1% and -15.2% +/- 1.7%, respectively (P < .001), and were similar to the post-oat bran bread values. Strawberries also improved the palatability of the diet. We conclude that strawberry supplementation reduced oxidative damage to LDL while maintaining reductions in blood lipids and enhancing diet palatability. Added fruit may improve the overall utility of diets designed to lower coronary heart disease risk.", "title": "The effect of strawberries in a cholesterol-lowering dietary portfolio." }, { "docid": "MED-4313", "text": "BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.", "title": "A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..." }, { "docid": "MED-3136", "text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.", "title": "Influence of frequent and long-term bean consumption on colonic function and fermentation." }, { "docid": "MED-2238", "text": "Rose G (Department of Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK). Sick individuals and sick populations. International Journal of Epidemiology 1985;14:32--38. Aetiology confronts two distinct issues: the determinants of individual cases, and the determinants of incidence rate. If exposure to a necessary agent is homogeneous within a population, then case/control and cohort methods will fail to detect it: they will only identify markers of susceptibility. The corresponding strategies in control are the 'high-risk' approach, which seeks to protect susceptible individuals, and the population approach, which seeks to control the causes of incidence. The two approaches are not usually in competition, but the prior concern should always be to discover and control the causes of incidence.", "title": "Sick individuals and sick populations." }, { "docid": "MED-2435", "text": "Breast cancer is the leading cause of cancer-related deaths in women in the United States and many other countries. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for many cancers, especially for breast cancer. Natural products are being tested with a hope of identifying novel potent molecules as anticancer agents. Phytochemicals and dietary compounds have been used for the treatment of various illnesses throughout history due to their safety, low toxicity, and general availability. Currently, many active phytochemicals are in clinical trials. Preclinical and clinical studies have indicated that daily consumption of dietary phytochemicals reduces the risk of several cancers. Phytochemicals can inhibit, delay, or reverse carcinogenesis by inducing detoxifying and antioxidant enzymes, by regulating inflammatory/proliferative signaling pathways, and by inducing apoptosis. This review article describes some of the potential natural cancer preventive compounds, along with a mechanistic discussion of their interactions with key cellular signal transduction pathways as well as their contribution to the suppression of breast cancer cell growth.", "title": "Chemoprevention of breast cancer by dietary compounds." }, { "docid": "MED-1966", "text": "Attempts to estimate the effects of dietary cholesterol on serum cholesterol by meta-analysis have not previously included baseline together with added dietary cholesterol in a mathematical model. Mean reported changes in serum cholesterol from 27 studies in which controlled diets were supplied by a metabolic kitchen provided 76 data points, each weighted by the number of subjects in nonlinear regression. A good fit to the data (P less than 0.0005, and r = 0.617 between observed and predicted points) was given by the equation y = 1.22(e-0.00384 chi 0) (1-e-0.0136 chi) where y is the change in serum cholesterol (in mmol/L), chi is added dietary cholesterol, and chi 0 is baseline dietary cholesterol (both in mg/d). Possible reasons for the hyperbolic shape of the relationship between change in serum cholesterol and added dietary cholesterol, mechanisms for individual responsiveness to dietary cholesterol, and important implications regarding interpretation of prior studies and public health issues are discussed.", "title": "Effects of dietary cholesterol on serum cholesterol: a meta-analysis and review." }, { "docid": "MED-1931", "text": "Caregivers of Alzheimer’s disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-α and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.", "title": "Accelerated Telomere Erosion Is Associated with a Declining Immune Function of Caregivers of Alzheimer’s Disease Patients" }, { "docid": "MED-1933", "text": "Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets “under the skin” remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress— both perceived stress and chronicity of stress—is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.", "title": "From the Cover: Accelerated telomere shortening in response to life stress" }, { "docid": "MED-3210", "text": "Folklore has suggested that consuming grapefruit may promote weight control. Sparse data exist to support this hypothesis, although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids. The aim of this randomized controlled trial was to prospectively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults (N = 74). Following a 3-week washout diet low in bioactive-rich fruits and vegetables, participants were randomized to either the control diet (n = 32) or daily grapefruit (n = 42) in the amount of one half of a fresh Rio-Red grapefruit with each meal (3× daily) for 6 weeks. No differences between group in weight, blood pressure, or lipids were demonstrated. Grapefruit consumption was associated with modest weight loss (-0.61 ± 2.23 kg, P = .097), a significant reduction in waist circumference (-2.45 ± 0.60 cm, P = .0002), and a significant reduction in systolic blood pressure (-3.21 ± 10.13 mm Hg, P = .03) compared with baseline values. Improvements were observed in circulating lipids of those consuming grapefruit, with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL (P = .002) and -18.7 mg/dL (P < .001), respectively, compared with baseline values. This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight, lipids, or blood pressure as compared with the control condition. However, the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults." }, { "docid": "MED-2083", "text": "Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.", "title": "Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation." }, { "docid": "MED-1617", "text": "Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.", "title": "Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women" }, { "docid": "MED-1556", "text": "Background: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. Objective: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Design: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. Results: During 5–23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. Conclusions: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.", "title": "Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease" }, { "docid": "MED-3429", "text": "Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction." }, { "docid": "MED-2587", "text": "Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a \"high-protein\" (high protein group/HPG) diet, which they believed would \"improve\" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p<0.001) significant. Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.", "title": "The effect of high-protein diets on coronary blood flow." }, { "docid": "MED-1249", "text": "The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.", "title": "Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women." }, { "docid": "MED-2077", "text": "Cardiovascular diseases are one of the leading causes of morbidity and mortality in industrialized countries, and although many processes play a role in the development of vascular disease, thrombosis is the primary event that precipitates stroke and acute coronary syndromes. The blood platelets are of significant importance in medicine. These cells are involved in many physiological processes, particularly haemostasis through their ability to aggregate and form clots in response to activation. In addition, these dynamic cells display activities that extend beyond thrombosis, including an important role in initiating and sustaining vascular inflammation. The expansion of knowledge from basic and clinical research has highlighted the critical position of platelets in several inflammatory diseases such as arthritis and atherosclerosis. Platelets are emerging as important mediators of inflammation and provide important signals to mediate phenotype of other blood and vascular cells. The important role of platelets in arterial thrombosis and the onset of acute myocardial infarction after atherosclerotic plaque rupture make inhibition of platelet aggregation a critical step in preventing thrombotic events associated with stroke, heart attack, and peripheral arterial thrombosis. However, the use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. The aim of this review is to up-date the knowledge on platelets physiology and dysfunction in pathologies, such as diabetes mellitus, hypercholesterolemia, and hypertension, emphasizing the link between platelets and the inflammation-related atherosclerosis. The review evaluates the opportunities offered by the novel platelet inhibitors to efficiently alleviate the thrombotic events. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Platelet dysfunction in vascular pathologies and how can it be treated." }, { "docid": "MED-2218", "text": "OBJECTIVE: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. DESIGN AND SETTING: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. PARTICIPANTS: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. MAIN OUTCOME MEASURES: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. RESULTS: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. CONCLUSIONS: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.", "title": "Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study." }, { "docid": "MED-2698", "text": "BACKGROUND AND PURPOSE: Consumption of antioxidant-rich foods may reduce the risk of stroke by inhibition of oxidative stress and inflammation. Total antioxidant capacity (TAC) takes into account all antioxidants and the synergistic effects between them. We examined the association between dietary TAC and stroke incidence in cardiovascular disease (CVD)-free women and in women with CVD history at baseline. METHODS: The study included women (31,035 CVD-free and 5680 with CVD history at baseline), aged 49 to 83 years, from the Swedish Mammography Cohort. Diet was assessed with a food frequency questionnaire. Dietary TAC was calculated using oxygen radical absorbance capacity values. Stroke cases were ascertained by linkage with the Swedish Hospital Discharge Registry. RESULTS: During follow-up (September 1997 to December 2009), we identified 1322 stroke cases (988 cerebral infarctions, 226 hemorrhagic strokes, and 108 unspecified strokes) among CVD-free women and 1007 stroke cases (796 cerebral infarctions, 100 hemorrhagic strokes, and 111 unspecified strokes) among women with a CVD history. The multivariable hazard ratio of total stroke comparing the highest with the lowest quintile of dietary TAC was 0.83 (95% CI, 0.70-0.99; P for trend=0.04) in CVD-free women. Among women with a CVD history, the hazard ratios for the highest versus lowest quartile of TAC were 0.90 (95% CI, 0.75-1.07; P for trend=0.30) for total stroke and 0.55 (95% CI, 0.32-0.95; P for trend=0.03) for hemorrhagic stroke. CONCLUSIONS: These findings suggest that dietary TAC is inversely associated with total stroke among CVD-free women and hemorrhagic stroke among women with CVD history.", "title": "Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women." }, { "docid": "MED-2590", "text": "Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.", "title": "Reversing heart disease in the new millennium--the Fleming unified theory." }, { "docid": "MED-4295", "text": "Phytosterols were quantified in nuts and seeds commonly consumed in the United States. Total lipid extracts were subjected to acid hydrolysis and then alkaline saponfication, and free sterols were analyzed as trimethylsilyl derivatives by capillary GC-FID and GC-MS. Delta5-Avenasterol was quantified after alkaline saponification plus direct analysis of the glucoside. Sesame seed and wheat germ had the highest total phytosterol content (400-413 mg/100 g) and Brazil nuts the lowest (95 mg/100 g). Of the products typically consumed as snack foods, pistachio and sunflower kernel were richest in phytosterols (270-289 mg/100 g). beta-Sitosterol, Delta5-avenasterol, and campesterol were predominant. Campestanol ranged from 1.0 to 12.7 mg/100 g. Only 13 mg/100 g beta-sitosterol was found in pumpkin seed kernel, although total sterol content was high (265 mg/100 g). Phytosterol concentrations were greater than reported in existing food composition databases, probably due to the inclusion of steryl glycosides, which represent a significant portion of total sterols in nuts and seeds.", "title": "Phytosterol composition of nuts and seeds commonly consumed in the United States." }, { "docid": "MED-1262", "text": "Background Medical nutrition therapy is recognized as an important treatment option in type 2 diabetes. Most guidelines recommend eating a diet with a high intake of fiber-rich food including fruit. This is based on the many positive effects of fruit on human health. However some health professionals have concerns that fruit intake has a negative impact on glycemic control and therefore recommend restricting the fruit intake. We found no studies addressing this important clinical question. The objective was to investigate whether an advice to reduce the intake of fruit to patients with type 2 diabetes affects HbA1c, bodyweight, waist circumference and fruit intake. Methods This was an open randomized controlled trial with two parallel groups. The primary outcome was a change in HbA1c during 12 weeks of intervention. Participants were randomized to one of two interventions; medical nutrition therapy + advice to consume at least two pieces of fruit a day (high-fruit) or medical nutrition therapy + advice to consume no more than two pieces of fruit a day (low-fruit). All participants had two consultations with a registered dietitian. Fruit intake was self-reported using 3-day fruit records and dietary recalls. All assessments were made by the “intention to treat” principle. Results The study population consisted of 63 men and women with newly diagnosed type 2 diabetes. All patients completed the trial. The high-fruit group increased fruit intake with 125 grams (CI 95%; 78 to 172) and the low-fruit group reduced intake with 51 grams (CI 95%; -18 to −83). HbA1c decreased in both groups with no difference between the groups (diff.: 0.19%, CI 95%; -0.23 to 0.62). Both groups reduced body weight and waist circumference, however there was no difference between the groups. Conclusions A recommendation to reduce fruit intake as part of standard medical nutrition therapy in overweight patients with newly diagnosed type 2 diabetes resulted in eating less fruit. It had however no effect on HbA1c, weight loss or waist circumference. We recommend that the intake of fruit should not be restricted in patients with type 2 diabetes. Trial registration http://www.clinicaltrials.gov; Identifier: NCT01010594.", "title": "Effect of fruit restriction on glycemic control in patients with type 2 diabetes – a randomized trial" }, { "docid": "MED-2699", "text": "Significance: The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology. Recent Advances: Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise. Critical Issues: A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity. Future Directions: Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding. Antioxid. Redox Signal. 19, 779–787.", "title": "The Free Radical Theory of Aging Revisited: The Cell Signaling Disruption Theory of Aging" }, { "docid": "MED-3819", "text": "Adiponectin is discussed to regulate energy balance and insulin sensitivity. Several studies indicated an association of fasting adiponectin with parameters of the metabolic syndrome. We investigated postprandial adiponectin release and its relation to traits of the metabolic syndrome. Serum adiponectin concentration after an oral glucose tolerance test and after ingestion of a standardised mixed, fat-containing meal in 110 male non-diabetic subjects was assessed. Fasting and postprandial adiponectin and the decrease of adiponectin were correlated with anthropometric and metabolic parameters. Subjects were genotyped for adiponectin - 11 388 G/A promoter single nucleotide polymorphism. Adiponectin slightly decreased after both test meals. A significant decrease was attained 5 and 6 h after the lipid load and 2 h after the glucose load. Particularly, the mixed meal postprandial adiponectin showed stronger correlations with most traits of the metabolic syndrome than fasting adiponectin: postprandial adiponectin with HDL (r 0.30) v. fasting adiponectin with HDL (r 0.23); with postprandial insulin (area under the curve): r - 0.20 v. r - 0.16; with fasting insulin: r 0.10 v. r 0.14; with BMI: r - 0.23 v. r - 0.20; with waist: r - 0.18 v. - 0.16; with systolic blood pressure: r - 0.14 v. r - 0.12; with diastolic blood pressure: r - 0.18 v. r - 0.15. In multivariate analysis, postprandial TAG were the only independent predictor of adiponectin. There was no significant association of adiponectin, NEFA and TAG with - 11 388 G/A adiponectin promoter polymorphism. Our findings favour the interpretation that postprandial adiponectin has the strongest and independent associations to postprandial TAG metabolism.", "title": "Postprandial plasma adiponectin decreases after glucose and high fat meal and is independently associated with postprandial triacylglycerols but no..." }, { "docid": "MED-4026", "text": "AIM: The aim of this study was to investigate possible risk factors for dental caries in primary school children. METHODS: Children aged 10-12 years (n = 257) residing in Lithgow, a non-fluoridated community in New South Wales, Australia, were examined for caries experience in the permanent dentition. Information on dental practices, diet, residential movements, and socioeconomic status were obtained from self-completed questionnaires. RESULTS: Caries risk in the permanent teeth was associated with social disadvantage and diet. Among the dietary factors, the frequency of fruit consumption was associated with higher odds of caries experience (odds ratio: 1.52, 95% confidence intervals: 1.05, 2.21). CONCLUSIONS: Exposure to a high level of fruit consumption was suggestive of increased caries risk. Longitudinal studies are required to investigate the relationship between fruit consumption and dental caries. © 2011 Blackwell Publishing Asia Pty Ltd.", "title": "Is the consumption of fruit cariogenic?" }, { "docid": "MED-2438", "text": "Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.", "title": "The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control st..." }, { "docid": "MED-2999", "text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.", "title": "Western diseases and their emergence related to diet." }, { "docid": "MED-1259", "text": "We sought to determine whether consumption of blueberries could reduce postprandial oxidation when consumed with a typical high-carbohydrate, low-fat breakfast. Participants (n 14) received each of the three treatments over 3 weeks in a cross-over design. Treatments consisted of a high blueberry dose (75 g), a low blueberry dose (35 g) and a control (ascorbic acid and sugar content matching that of the high blueberry dose). Serum oxygen radical absorbance capacity (ORAC), serum lipoprotein oxidation (LO) and serum ascorbate, urate and glucose were measured at fasting, and at 1, 2 and 3 h after sample consumption. The mean serum ORAC was significantly higher in the 75 g group than in the control group during the first 2 h postprandially, while serum LO lag time showed a significant trend over the 3 h for both blueberry doses. Changes in serum ascorbate, urate and glucose were not significantly different among the groups. To our knowledge, this is the first report that has demonstrated that increased serum antioxidant capacity is not attributable to the fructose or ascorbate content of blueberries. In summary, a practically consumable quantity of blueberries (75 g) can provide statistically significant oxidative protection in vivo after a high-carbohydrate, low-fat breakfast. Though not tested directly, it is likely that the effects are due to phenolic compounds, either directly or indirectly, as they are a major family of compounds in blueberries with potential bioactive activity.", "title": "Consumption of blueberries with a high-carbohydrate, low-fat breakfast decreases postprandial serum markers of oxidation." }, { "docid": "MED-1928", "text": "Purpose of review There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening. Recent findings Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases. Summary Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging.", "title": "Telomeres, lifestyle, cancer, and aging" }, { "docid": "MED-2525", "text": "AIMS: Guidelines for cardiovascular disease (CVD) prevention cite high levels of low-density lipoprotein cholesterol (LDL-C) as a major risk factor and recommend LDL-C goals for various risk groups. Lifestyle changes are advised as first-line treatment for patients with high cholesterol, and statins are recommended in high-risk patients. The From The Heart study investigated current practice for the diagnosis and treatment of high cholesterol, and attitudes towards management of the condition. METHODS: Physicians were randomly selected from 10 countries, and completed a confidential, semi-structured questionnaire. RESULTS: Of 2790 physicians agreeing to participate, 750 (27%) responded. Physicians rated CVD as the leading cause of death, although physicians (80%) perceived that cancer was the most feared illness among patients. Physicians (71%) believed smoking to be the greatest CVD risk factor, while only 50% thought high cholesterol was the greatest risk. Most physicians (81%) used guidelines to set cholesterol goals, primarily their national guidelines (34%) or the National Cholesterol Education Program Adult Treatment Panel III guidelines (24%). Although only 47% of patients reached and maintained their cholesterol goals, 61% of physicians believed that a sufficient number of patients achieved goals, and 53% did not feel frustrated that they could not always effectively treat patients with CVD. CONCLUSION: Results indicate discrepancies between guideline recommendations and clinical practice. Although physicians appreciate the risk of CVD, the importance of achieving healthy cholesterol levels for CVD prevention does not seem to be widely endorsed. There is a need for improved communication regarding the importance of cholesterol lowering and investigation of initiatives to improve goal achievement among physicians.", "title": "A global survey of physicians' perceptions on cholesterol management: the From The Heart study." }, { "docid": "MED-2696", "text": "A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35-70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46-0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43-0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22-0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28-0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21-0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC. Copyright © 2011 UICC.", "title": "Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study." }, { "docid": "MED-2695", "text": "BACKGROUND: There are no previous studies investigating the effect of all dietary antioxidants in relation to myocardial infarction. The total antioxidant capacity of diet takes into account all antioxidants and synergistic effects between them. The aim of this study was to examine how total antioxidant capacity of diet and antioxidant-containing foods were associated with incident myocardial infarction among middle-aged and elderly women. METHODS: In the population-based prospective Swedish Mammography Cohort of 49-83-year-old women, 32,561 were cardiovascular disease-free at baseline. Women completed a food-frequency questionnaire, and dietary total antioxidant capacity was calculated using oxygen radical absorbance capacity values. Information on myocardial infarction was identified from the Swedish Hospital Discharge and the Cause of Death registries. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models. RESULTS: During the follow-up (September 1997-December 2007), we identified 1114 incident cases of myocardial infarction (321,434 person-years). In multivariable-adjusted analysis, the HR for women comparing the highest quintile of dietary total antioxidant capacity to the lowest was 0.80 (95% CI, 0.67-0.97; P for trend=0.02). Servings of fruit and vegetables and whole grains were nonsignificantly inversely associated with myocardial infarction. CONCLUSIONS: These data suggest that dietary total antioxidant capacity, based on fruits, vegetables, coffee, and whole grains, is of importance in the prevention of myocardial infarction. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Total antioxidant capacity from diet and risk of myocardial infarction: a prospective cohort of women." }, { "docid": "MED-4562", "text": "OBJECTIVES: The study aimed to analyze the use of intensive lipid-lowering therapy (LLT) at discharge in a broad population of patients hospitalized with acute coronary syndrome (ACS). BACKGROUND: Early and intensive statin therapy in ACS was shown to reduce cardiovascular morbidity and mortality. Utilization and predictors of LLT among hospitalized ACS patients are not known. METHODS: The GWTG database was analyzed for ACS-related hospitalizations from 2005 to 2009. The use of LLT (defined as dose of statin or combination therapy likely to produce>50% reductions in low-density lipoprotein [LDL]) and less intensive LLT at discharge was assessed. Baseline characteristics and temporal trends in LLT were compared in these 2 treatment groups. RESULTS: Of 65,396 patients receiving LLT, only 25,036 (38.3%) were treated with an LLT regimen. Mean total cholesterol, LDL, and triglycerides were significantly higher in the LLT group. Even among those with LDL>130 mg/dL, 50% or less received LLT. Predictors of LLT at discharge included LLT before admission, hyperlipidemia, prior coronary artery disease, increasing body mass index, and in-hospital percutaneous coronary intervention. Although there was some temporal improvement in the rate of LLT from 2005 to 2007, a decline in use of LLT was noted in 2008 and 2009. This was attributed to a sharp reduction in use of ezetimibe in combination with statin, without corresponding increases in intensive statin monotherapy. CONCLUSIONS: In a large cohort of patients admitted with ACS, most of the eligible patients were not discharged on LLT. These data suggest the need for better implementation of guideline-recommended intensive statin therapy in patients with ACS. Published by Mosby, Inc.", "title": "Use of intensive lipid-lowering therapy in patients hospitalized with acute coronary syndrome: an analysis of 65,396 hospitalizations from 344 hosp..." }, { "docid": "MED-1620", "text": "Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767", "title": "A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women" }, { "docid": "MED-3142", "text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.", "title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China." }, { "docid": "MED-2693", "text": "Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The Oxygen Radical Absorbance Capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements, and FFQ-based ORAC values are associated with a lower risk of NHL in a clinic-based study of 603 incident cases and 1007 frequency-matched controls. Diet was assessed with a 128-item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of α-tocopherol (OR=0.50; p-trend=0.0002), β-carotene (OR=0.58; p-trend=0.0005), lutein/zeaxanthin (OR=0.62; p-trend=0.005), zinc (OR=0.54; p-trend=0.003) and chromium (OR=0.68; p-trend=0.032) were inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR=0.52; p-trend<0.0001), particularly green leafy (OR=0.52; p-trend<0.0001) and cruciferous (OR=0.68; p-trend=0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR=0.61, p-trend=0.003) and lipophilic ORAC (OR=0.48, p-trend=0.0002), although after simultaneous adjustment for other antioxidants or total vegetables only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ-ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake.", "title": "Food-Frequency Questionnaire Based Estimates of Total Antioxidant Capacity and Risk of Non-Hodgkin Lymphoma" }, { "docid": "MED-2850", "text": "Background: Fatty acids play a vital role in glucose homeostasis; however, studies on habitual dietary fat intakes and gestational diabetes mellitus (GDM) risk are limited and provide conflicting findings. Objective: We determined whether the total amount and the type and source of prepregnancy dietary fats are related to risk of GDM. Design: A prospective study was conducted in 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. In these women, 860 incident GDM cases were reported. The adjusted RR of GDM was estimated for quintiles of total fat, specific fat, and the source of fat intakes by pooled logistic regression. Results: Higher animal fat and cholesterol intakes were significantly associated with increased GDM risk. Across increasing quintiles of animal fat, RRs (95% CIs) for GDM were 1.00 (reference), 1.55 (1.20, 1.98), 1.43 (1.09, 1.88), 1.40 (1.04, 1.89), and 1.88 (1.36, 2.60) (P-trend = 0.05). Corresponding RRs (95% CIs) for dietary cholesterol were 1.00 (reference), 1.08 (0.84, 1.32), 1.02 (0.78, 1.29), 1.20 (0.93, 1.55), and 1.45 (1.11, 1.89) (P-trend = 0.04). The substitution of 5% of energy from animal fat for an equal percentage of energy from carbohydrates was associated with significantly increased risk of GDM [RR (95% CI): 1.13 (1.08, 1.18); P < 0.0001]. No significant associations were observed between dietary polyunsaturated fat, monounsaturated fat, or trans fat intakes and GDM risk. Conclusion: Higher prepregnancy intakes of animal fat and cholesterol were associated with elevated GDM risk.", "title": "A prospective study of prepregnancy dietary fat intake and risk of gestational diabetes" }, { "docid": "MED-2704", "text": "Lipid peroxidation is, in most instances, a free radical chain reaction that can be described in terms of initiation, propagation, branching and termination processes. With regard to lipid peroxidation, one of the most important questions concerns the source of the primary catalysts that initiate peroxidation in situ in muscle foods. When cells are injured, such as in muscle foods after slaughtering, lipid peroxidation is favored, and traces of O(2) and H(2)O(2), indicating lipid peroxides, are formed. The stability of a muscle food product will depend on the 'tone' of these peroxides and especially from the involvement of metal ions in the process. The cytosol contains not only prooxidants but also antioxidants and the tone of both affects the overall oxidation. Lipid peroxidation is one of the primary mechanisms of quality deterioration in foods and especially in meat products. The changes in quality can be manifested by deterioration in flavor, color, texture, nutritive value and the production of toxic compounds. Copyright © 1993. Published by Elsevier Ltd.", "title": "Oxidative processes in meat and meat products: Quality implications." }, { "docid": "MED-5014", "text": "Several nutrition and non-nutritional pathways are recognised in the development and occurrence of cardiovascular disease. In many populations, high intakes of saturated fat are associated with elevated serum cholesterol concentrations and increased coronary heart disease (CHD) mortality. However, several studies report that hyperlipidaemia and heart diseases are not common among populations who consume coconut, a source of saturated fat. A case-control study was conducted among the Minangkabau known to be high coconut consumers to examine the difference in food patterns and risk of coronary heart disease (CHD) between the coronary cases and their gender- and age-matched apparently healthy counterparts serving as controls. Eligible subjects with CHD were identified through the co-operation of five participating hospitals located in Padang and Bukittinggi in West Sumatra, Indonesia. A total of 93 eligible cases (62 men and 31 women) in the Case group and 189 subjects (113 men and 76 women) in the Control group were recruited. Information on the intakes of individual foods and dishes over the preceding 12 months was obtained using a semi-quantitative food frequency questionnaire. The Case groups had significantly higher intakes of meats, eggs, sugar, tea, coffee and fruits, but lower intakes of soy products, rice and cereals compared to the controls. Coconut consumption as flesh or milk was not different between cases and controls. The cases had significantly higher intakes of protein and cholesterol, but lower intake of carbohydrate. Similar intakes of saturated and unsaturated fatty acids between the cases and controls indicated that the consumption of total fat or saturated fat, including that from coconut, was not a predictor for CHD in this food culture. However, the intakes of animal foods, total protein, dietary cholesterol and less plant derived carbohydrates were predictors of CHD.", "title": "Dietary intake and the risk of coronary heart disease among the coconut-consuming Minangkabau in West Sumatra, Indonesia." }, { "docid": "MED-2432", "text": "It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.", "title": "The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century." }, { "docid": "MED-1551", "text": "In a controlled trial, 21 strict vegetarians were studied prospectively for eight weeks: a two-week control period of the usual vegetarian diet was followed by four weeks, during which 250 g of beef was added isocalorically to the daily vegetarian diet and then by two weeks of the control diet. Plasma high-density lipoprotein-cholesterol did not change during the study, whereas plasma total cholesterol rose significantly by 19% at the end of the meat-eating period. Systolic blood pressure (BP) increased significantly during the meat eating by 3% over control values, whereas diastolic BP showed no major changes. Plasma renin activity, prostaglandin A and E levels, and urinary kallikrein, norepinephrine, and epinephrine excretions were within normal limits and did not change notably throughout the trial. The study suggests an adverse effect of consumption of beef on plasma lipid and BP levels.", "title": "Effect of ingestion of meat on plasma cholesterol of vegetarians." }, { "docid": "MED-3427", "text": "Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "The link between erectile and cardiovascular health: the canary in the coal mine." }, { "docid": "MED-2429", "text": "Emerging evidence suggests that statins' may decrease the risk of cancers. However, available evidence on breast cancer is conflicting. We, therefore, examined the association between statin use and risk of breast cancer by conducting a detailed meta-analysis of all observational studies published regarding this subject. PubMed database and bibliographies of retrieved articles were searched for epidemiological studies published up to January 2012, investigating the relationship between statin use and breast cancer. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Combined relative risk (RR) and 95 % confidence interval (CI) were calculated using a random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 24 (13 cohort and 11 case-control) studies involving more than 2.4 million participants, including 76,759 breast cancer cases contributed to this analysis. We found no evidence of publication bias and evidence of heterogeneity among the studies. Statin use and long-term statin use did not significantly affect breast cancer risk (RR = 0.99, 95 % CI = 0.94, 1.04 and RR = 1.03, 95 % CI = 0.96, 1.11, respectively). When the analysis was stratified into subgroups, there was no evidence that study design substantially influenced the effect estimate. Sensitivity analysis confirmed the stability of our results. Cumulative meta-analysis showed a change in trend of reporting risk of breast cancer from positive to negative in statin users between 1993 and 2011. Our meta-analysis findings do not support the hypothesis that statins' have a protective effect against breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.", "title": "Statin use and risk of breast cancer: a meta-analysis of observational studies." }, { "docid": "MED-3113", "text": "Chronic diseases with a lifestyle-based aetiology currently make up a significant proportion of primary care consultations, but management often falls between the demands of public and clinical health. A modified clinical approach, based around the concept of \"lifestyle medicine\", helps fill the gap by adding behavioural, motivational and environmental skills to conventional medical practice. When used in a multidisciplinary setting, lifestyle medicine offers potential cost and effectiveness benefits, which are beginning to be realised.", "title": "The emergence of \"lifestyle medicine\" as a structured approach for management of chronic disease." }, { "docid": "MED-1916", "text": "BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.", "title": "The association between physical activity in leisure time and leukocyte telomere length." }, { "docid": "MED-2214", "text": "Summary Background 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. Methods 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. Findings Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24·3 million people have dementia today, with 4·6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81·1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. Interpretation We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.", "title": "Global prevalence of dementia: a Delphi consensus study" }, { "docid": "MED-3818", "text": "BACKGROUND: Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. METHODS: A total of 15 lean (body mass index [BMI] < 25 kg/m(2) ) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. RESULTS: Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6 ± 3.1 AU versus 16.6 ± 4.1 AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3 ± 7.3 μg/ml) and without (19.3 ± 6.1 μg/ml) cellulite (P=0.69). CONCLUSIONS: Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue. © 2011 The International Society of Dermatology.", "title": "Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite." }, { "docid": "MED-1674", "text": "What do the Atkins Diet and the traditional Japanese diet have in common? The Atkins Diet is low in carbohydrate and usually high in fat; the Japanese diet is high in carbohydrate and usually low in fat. Yet both work to promote weight loss. One commonality of both diets is that they both eliminate the monosaccharide fructose. Sucrose (table sugar) and its synthetic sister high fructose corn syrup consist of 2 molecules, glucose and fructose. Glucose is the molecule that when polymerized forms starch, which has a high glycemic index, generates an insulin response, and is not particularly sweet. Fructose is found in fruit, does not generate an insulin response, and is very sweet. Fructose consumption has increased worldwide, paralleling the obesity and chronic metabolic disease pandemic. Sugar (i.e., fructose-containing mixtures) has been vilified by nutritionists for ages as a source of “empty calories,” no different from any other empty calorie. However, fructose is unlike glucose. In the hypercaloric glycogen-replete state, intermediary metabolites from fructose metabolism overwhelm hepatic mitochondrial capacity, which promotes de novo lipogenesis and leads to hepatic insulin resistance, which drives chronic metabolic disease. Fructose also promotes reactive oxygen species formation, which leads to cellular dysfunction and aging, and promotes changes in the brain’s reward system, which drives excessive consumption. Thus, fructose can exert detrimental health effects beyond its calories and in ways that mimic those of ethanol, its metabolic cousin. Indeed, the only distinction is that because fructose is not metabolized in the central nervous system, it does not exert the acute neuronal depression experienced by those imbibing ethanol. These metabolic and hedonic analogies argue that fructose should be thought of as “alcohol without the buzz.”", "title": "Fructose: It’s “Alcohol Without the Buzz”" }, { "docid": "MED-3816", "text": "Most of adult women exhibit cellulite on the hips, buttock and thighs. Although extracellular matrix and lymphatic system disorders can increase its appearance, cellulite basically results from an excessive fat storage in the adipose tissue which exerts considerable pressure on the surrounding skin tissue and creates a dimpled irregular appearance. Caffeine, the most widely used anti-cellulite ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and encouraging a high intracellular level of cAMP. A series of studies has shown that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage and slowed fat break-down in the adipose tissue. Besides, it was shown that heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To design a new cosmetic ingredient with anti-cellulite properties, we used molecular modelling to screen several ingredients with a structure similar to that of heparan sulfate glycosaminoglycans. This way, we identified sulfo-carrabiose as a potent molecule for trapping spermine and spermidine. These virtual results were first confirmed in tubo where sulfo-carrabiose was shown to dose-dependently inactivate spermine and spermidine. In vitro, adipocytes cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis and a significant increase of lipolysis. When sulfo-carrabiose was incorporated in a cosmetic formula, significant improvements were observed in thigh circumference, with better results than those obtained with caffeine after 28 days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to results significantly better than those obtained with caffeine alone. As measured by fringe projection, thigh volume was also significantly reduced after sulfo-carrabiose treatment. Finally, the appearance of cellulite assessed by clinical evaluation was also significantly reduced within 28 days. © 2010 BASF Beauty Care Solutions. ICS © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.", "title": "In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties." }, { "docid": "MED-2594", "text": "BACKGROUND: Epidemiologic studies have shown an inverse association between the frequency of nut consumption and body mass index (BMI) and risk of obesity. However, clinical trials that evaluated nut consumption on adiposity have been scarce and inconclusive. OBJECTIVE: We performed a systematic review and meta-analysis of published, randomized nut-feeding trials to estimate the effect of nut consumption on adiposity measures. DESIGN: MEDLINE and the Cochrane Central Register of Controlled Trials databases were searched for relevant clinical trials of nut intake that provided outcomes of body weight, BMI (in kg/m(2)), or waist-circumference measures and were published before December 2012. There were no language restrictions. Two investigators independently selected and reviewed eligible studies. The weighted mean difference (WMD) between nut or control diets was estimated by using a random-effects meta-analysis with 95% CIs. RESULTS: Thirty-three clinical trials met our inclusion criteria. Pooled results indicated a nonsignificant effect on body weight (WMD: -0.47 kg; 95% CI: -1.17, 0.22 kg; I(2) = 7%), BMI (WMD: -0.40 kg/m(2); 95% CI: -0.97, 0.17 kg/m(2); I(2) = 49%), or waist circumference (WMD: -1.25 cm; 95% CI: -2.82, 0.31 cm; I(2) = 28%) of diets including nuts compared with control diets. These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. CONCLUSION: Compared with control diets, diets enriched with nuts did not increase body weight, body mass index, or waist circumference in controlled clinical trials.", "title": "Nut intake and adiposity: meta-analysis of clinical trials." }, { "docid": "MED-3251", "text": "CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.", "title": "Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis." }, { "docid": "MED-3397", "text": "INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (Viagra(R)), tadalafil (Cialis(R)), and vardenafil (Levitra(R)) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3-11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. AIMS: To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. METHODS: Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. MAIN OUTCOME MEASURES: To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. RESULTS: Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. CONCLUSION: There is lack of conclusive evidence to indicate a direct cause-effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3-11% of users and they are transient and reversible. © 2011 International Society for Sexual Medicine.", "title": "Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A critical analysis and review of the literature." }, { "docid": "MED-5293", "text": "Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.", "title": "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010" }, { "docid": "MED-3399", "text": "We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.", "title": "Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction." }, { "docid": "MED-5117", "text": "PURPOSE: Because they have large variations in consumption, Asian countries are suitable settings for studies of the effect of relatively high-dose isoflavone intake on breast cancer risk. Nevertheless, no prospective study from Asia has assessed blood or urine levels as biomarkers of isoflavone intake. PATIENTS AND METHODS: A total of 24,226 women ages 40 to 69 years in the Japan Public Health Center-based prospective study who responded to the baseline questionnaire and provided blood in 1990 to 1995 were observed to December 2002. During a mean 10.6 years of follow-up, 144 patients newly diagnosed with breast cancer were identified. Two matched controls for each patient were selected from the cohort. Isoflavone levels were assessed by plasma level and food frequency questionnaire, and the odds ratio of breast cancer according to isoflavone level was estimated using a conditional logistic regression model. RESULTS: We found a statistically significant inverse association between plasma genistein and risk of breast cancer, but no association for plasma daidzein. Adjusted odds ratios for the highest versus lowest quartile of plasma level were 0.34 for genistein (95% CI, 0.16 to 0.74; P for trend, .02) and 0.71 for daidzein (95% CI, 0.35 to 1.44; P for trend, .54). Median plasma genistein values in the control group were 31.9 ng/mL for the lowest and 353.9 ng/mL for the highest quartile groups. Regarding dietary intake of isoflavones, nonsignificant inverse associations were observed for both genistein and daidzein. CONCLUSION: This nested case-control study found an inverse association between plasma genistein and the risk of breast cancer in Japan.", "title": "Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-..." }, { "docid": "MED-2440", "text": "Purpose To further clarify the relationship between total cholesterol and cancer, which remains unclear. Methods We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death. Results Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (≥ 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend ≤ .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001). Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32). Conclusion In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site.", "title": "Total Cholesterol and Cancer Risk in a Large Prospective Study in Korea" }, { "docid": "MED-5081", "text": "Background Raisins are a significant source of dietary fiber and polyphenols, which may reduce cardiovascular disease (CVD) risk by affecting lipoprotein metabolism and inflammation. Walking represents a low intensity exercise intervention that may also reduce CVD risk. The purpose of this study was to determine the effects of consuming raisins, increasing steps walked, or a combination of these interventions on blood pressure, plasma lipids, glucose, insulin and inflammatory cytokines. Results Thirty-four men and postmenopausal women were matched for weight and gender and randomly assigned to consume 1 cup raisins/d (RAISIN), increase the amount of steps walked/d (WALK) or a combination of both interventions (RAISINS + WALK). The subjects completed a 2 wk run-in period, followed by a 6 wk intervention. Systolic blood pressure was reduced for all subjects (P = 0.008). Plasma total cholesterol was decreased by 9.4% for all subjects (P < 0.005), which was explained by a 13.7% reduction in plasma LDL cholesterol (LDL-C) (P < 0.001). Plasma triglycerides (TG) concentrations were decreased by 19.5% for WALK (P < 0.05 for group effect). Plasma TNF-α was decreased from 3.5 ng/L to 2.1 ng/L for RAISIN (P < 0.025 for time and group × time effect). All subjects had a reduction in plasma sICAM-1 (P < 0.01). Conclusion This research shows that simple lifestyle modifications such as adding raisins to the diet or increasing steps walked have distinct beneficial effects on CVD risk.", "title": "Raisins and additional walking have distinct effects on plasma lipids and inflammatory cytokines" }, { "docid": "MED-2938", "text": "Since the adoption of vegetarian diets as a healthy lifestyle has become popular, the cardiovascular effects of long-term vegetarianism need to be explored. The present study aimed to compare the presence and severity of carotid atherosclerosis (CA), and the blood levels of Vitamin B12, homocysteine (Hcy) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between 57 healthy postmenopausal vegetarians and 61 age-matched omnivores. Carotid atherosclerosis, as measured by ultrasound, was found to be of no significant difference between the two groups. Yet, fasting blood glucose, low-density lipoprotein cholesterol, and Vitamin B12 were significantly lower, while Hcy and sVCAM-1 were higher in the vegetarians as comparing with the omnivores. Multivariate regression analysis showed that the level of Vitamin B12 was negatively associated with the level of Hcy. Vegetarianism itself and Hcy level were significantly associated with sVCAM-1 level in univariate analysis; however, after adjustment for covariates, we identified age but not vegetarianism as the determinant of sVCAM-1 level. Multiple linear regression analysis identified age and systolic blood pressure, but not vegetarianism, as determinants of common carotid artery IMT. In conclusion, there was no significant difference in CA between apparently healthy postmenopausal vegetarians and omnivores. The findings of elevated Hcy in vegetarians indicate the importance of prevention of Vitamin B12 deficiency.", "title": "Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmenopausal vegetarian women and omnivores." }, { "docid": "MED-3123", "text": "DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption." }, { "docid": "MED-2702", "text": "BACKGROUND: Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality. METHODS: With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs. FINDINGS: We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer. INTERPRETATION: We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.", "title": "Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis." }, { "docid": "MED-2939", "text": "Background: Vegetarianism is associated with a lower risk of cardiovascular disease. However, studies of arterial function in vegetarians are limited. Methods: This study investigated arterial function in vegetarianism by comparing 49 healthy postmenopausal vegetarians with 41 age-matched omnivores. The arterial function of the common carotid artery was assessed by carotid duplex, while the pulse dynamics method was used to measure brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR). Fasting blood levels of glucose, lipids, lipoprotein (a), high-sensitivity C-reactive protein, homocysteine, and vitamin B12 were also measured. Results: Vegetarians had significantly lower serum cholesterol, high-density and low-density lipoprotein, and glucose compared with omnivores. They also had lower vitamin B12 but higher homocysteine levels. Serum levels of lipoprotein (a) and high-sensitivity C-reactive protein were no different between the two groups. There were no significant differences in carotid beta stiffness index, BAC, and BAD between the two groups even after adjustment for associated covariates. However, BAR was significantly lower in vegetarians than in omnivores. Multiple linear regression analysis revealed that age and pulse pressure were two important determinants of carotid beta stiffness index and BAD. Vegetarianism is not associated with better arterial elasticity. Conclusion: Apparently healthy postmenopausal vegetarians are not significantly better in terms of carotid beta stiffness index, BAC, and BAD, but have significantly decreased BAR than omnivores. Prevention of vitamin B12 deficiency might be beneficial for cardiovascular health in vegetarians.", "title": "Arterial function of carotid and brachial arteries in postmenopausal vegetarians" } ]	[ { "docid": "MED-5146", "text": "Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis. Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder (13, 19.5, and 26 g/d) in normocholesterolemic and mildly hypercholesterolemic humans. In this comparative, double-blind study, we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds (placebo-cocoa group) or 3 levels of cocoa powder containing high-polyphenolic compounds (13, 19.5, and 26 g/d for low-, middle-, and high-cocoa groups, respectively) for 4 wk. The test powders were consumed as a beverage after the addition of hot water, twice each day. Blood samples were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids. Plasma oxidized LDL concentrations decreased in the low-, middle-, and high-cocoa groups compared with baseline. A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of > or =3.23 mmol/L at baseline. In these subjects, plasma LDL cholesterol, oxidized LDL, and apo B concentrations decreased, and the plasma HDL cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups. The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol, an elevation in HDL cholesterol, and the suppression of oxidized LDL.", "title": "Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different leve..." }, { "docid": "MED-1193", "text": "Summary Background Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain. Methods This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated. Findings Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77–0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47–0·81], 0·69 [99% CI 0·60–0·79], 0·79 [99% CI 0·74–0·85], 0·81 [99% CI 0·77–0·86], and 0·79 [99% CI 0·74–0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36–0·89, p=0·0012, and 0·61, 99% CI 0·50–0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35–0·75, and 0·63, 99% CI 0·51–0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61–0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77–0·95) and all-cause mortality (RR 0·91, 95% CI 0·85–0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96–1·04), cancer mortality (RR 0·99, 95% CI 0·93–1·06), or other non-vascular mortality. Interpretation In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered. Funding British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.", "title": "The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials" }, { "docid": "MED-4298", "text": "Diet plays a seminal role in the prevention and treatment of cardiovascular disease. Consumption of tree nuts has been shown to reduce low-density lipoprotein cholesterol (LDL-C), a primary target for coronary disease prevention, by 3-19%. Almonds have been found to have a consistent LDL-C-lowering effect in healthy individuals, and in individuals with high cholesterol and diabetes, in both controlled and free-living settings. Almonds are low in saturated fatty acids, rich in unsaturated fatty acids, and contain fiber, phytosterols, and plant protein. Other cardioprotective nutrients unique to almonds include α-tocopherol, arginine, magnesium, copper, manganese, calcium, and potassium. Mechanisms responsible for the LDL-C reduction observed with almond consumption are likely associated with the nutrients almonds provide. Biologically active by nature, these nutrients target primary mechanistic routes of LDL-C reduction, including decreased (re)absorption of cholesterol and bile acid, increased bile acid and cholesterol excretion, and increased LDL-C receptor activity. The nutrients present in almonds may regulate enzymes involved in de novo cholesterol synthesis and bile acid production. Research is needed to understand all mechanisms by which almonds reduce cardiovascular disease risk. © 2011 International Life Sciences Institute.", "title": "Effects of almond consumption on the reduction of LDL-cholesterol: a discussion of potential mechanisms and future research directions." }, { "docid": "MED-4296", "text": "Background/Objectives Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma LDL-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism. Subjects/Methods Twenty out of 24 subjects completed a randomized, crossover feeding trial where all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg/2000 kcal) but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatograph/mass spectrometry after oral administration of stable isotopic tracers. Results The phytosterol-abundant diet resulted in lower cholesterol absorption [54.2 ± 2.2 % (95% confidence interval, 50.5%, 57.9%) vs. 73.2 ± 1.3% (69.5%, 76.9%), P<0.0001] and 79% higher fecal cholesterol excretion [1322 ± 112 (1083.2, 1483.3) vs. 739 ± 97 mg/day (530.1, 930.2), P<0.0001] relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose 82% [from 0.71 ± 0.11 (0.41, 0.96) to 1.29 ± 0.14 μg/mg (0.98, 1.53), (P<0.0001)]. LDL-cholesterol was similar between diets. Conclusions Intrinsic phytosterols at levels present in a healthy diet are biologically active and have large effects on whole body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.", "title": "The Effects of Phytosterols Present in Natural Food Matrices on Cholesterol Metabolism and LDL-Cholesterol: A Controlled Feeding Trial" }, { "docid": "MED-5149", "text": "BACKGROUND: Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis. OBJECTIVE: We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects. DESIGN: Twenty-five subjects were randomly assigned to ingest either 12 g sugar/d (control group) or 26 g cocoa powder and 12 g sugar/d (cocoa group) for 12 wk. Blood samples were collected before the study and 12 wk after intake of the test drinks. Plasma lipids, LDL oxidative susceptibility, and urinary oxidative stress markers were measured. RESULTS: At 12 wk, we measured a 9% prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group. This prolongation in the cocoa group was significantly greater than the reduction measured in the control group (-13%). A significantly greater increase in plasma HDL cholesterol (24%) was observed in the cocoa group than in the control group (5%). A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL. At 12 wk, there was a 24% reduction in dityrosine from baseline concentrations in the cocoa group. This reduction in the cocoa group was significantly greater than the reduction in the control group (-1%). CONCLUSION: It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol.", "title": "Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-c..." }, { "docid": "MED-5049", "text": "OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.", "title": "Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli..." }, { "docid": "MED-2008", "text": "Our purpose was to determine the effects of a pulse-based diet in individuals 50 years or older for reducing CVD risk factors. A total of 108 participants were randomised to receive pulse-based foods (two servings daily of beans, chickpeas, peas or lentils; about 150 g/d dry weight) or their regular diet for 2 months, followed by a washout of 1 month and a cross-over to the other diet for 2 months. Anthropometric measures, body composition and biochemical markers (i.e. serum LDL-cholesterol (LDL-C), as the primary outcome, and other lipids, glucose, insulin and C-reactive protein) were assessed before and after each diet phase. A total of eighty-seven participants (thirty males and fifty-seven females; 59·7 (sd 6·3) years, body mass 76 (sd 16) kg) completed the study. Compared with the regular diet, the pulse-based diet decreased total cholesterol by 8·3 % (pulse, 4·57 (sd 0·93) to 4·11 (sd 0·91) mmol/l; regular, 4·47 (sd 0·94) to 4·39 (sd 0·97) mmol/l; P < 0·001) and LDL-C by 7·9 % (pulse, 2·93 (sd 0·84) to 2·55 (sd 0·75) mmol/l; regular, 2·96 (sd 0·86) to 2·81 (sd 0·83) mmol/l; P = 0·01). In a sub-analysis of individuals with high lipid levels at baseline (twenty individuals with high cholesterol), the pulse-based diet reduced cholesterol by 6 % compared with the regular diet (pulse, 5·62 (sd 0·78) to 5·26 (sd 0·68) mmol/l; regular, 5·60 (sd 0·91) to 5·57 (sd 0·85) mmol/l; P = 0·05). A pulse-based diet is effective for reducing total cholesterol and LDL-C in older adults and therefore reduces the risk of CVD.", "title": "A pulse-based diet is effective for reducing total and LDL-cholesterol in older adults." }, { "docid": "MED-927", "text": "OBJECTIVE: To assess the effects of krill oil on blood lipids, specifically total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). METHODS: A multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up of patients treated with 1 g and 1.5 g krill oil daily. Patients with hyperlipidemia able to maintain a healthy diet and with blood cholesterol levels between 194 and 348 mg per dL were eligible for enrollment in the trial. A sample size of 120 patients (30 patients per group) was randomly assigned to one of four groups. Group A received krill oil at a body mass index (BMI)-dependent daily dosage of 2-3 g daily. Patients in Group B were given 1-1.5 g krill oil daily, and Group C was given fish oil containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) per gram of oil at a dose of 3 g daily. Group D was given a placebo containing microcrystalline cellulose. The krill oil used in this study was Neptune Krill Oil, provided by Neptune Technologies and Bioresources, Laval, Quebec, Canada. OUTCOME MEASURES: Primary parameters tested (baseline and 90-day visit) were total blood cholesterol, triglycerides, LDL, HDL, and glucose. RESULTS: Krill oil 1-3 g per day (BMI-dependent) was found to be effective for the reduction of glucose, total cholesterol, triglycerides, LDL, and HDL, compared to both fish oil and placebo. CONCLUSIONS: The results of the present study demonstrate within high levels of confidence that krill oil is effective for the management of hyperlipidemia by significantly reducing total cholesterol, LDL, and triglycerides, and increasing HDL levels. At lower and equal doses, krill oil was significantly more effective than fish oil for the reduction of glucose, triglycerides, and LDL levels.", "title": "Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia." }, { "docid": "MED-5178", "text": "Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied for their health benefits. An 8-week, randomised, double-blind, placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects, using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels. Significant treatment effects were achieved (P < 0.05 to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C) and glucose concentrations, as well as their percentage decrease from baseline. At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005 compared with placebo). For the 300 mg SDG group, only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8, especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P = 0.012 compared with placebo, respectively). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan. The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner.", "title": "Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects." }, { "docid": "MED-754", "text": "CONTEXT: Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions. OBJECTIVE: To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets. DESIGN, SETTING, AND PARTICIPANTS: A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months. INTERVENTION: Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months. MAIN OUTCOME MEASURES: Percentage change in serum LDL-C. RESULTS: In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P < .001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001). CONCLUSION: Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.", "title": "Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a r..." }, { "docid": "MED-1663", "text": "STUDY DESIGN: A cross-sectional analysis of the feeding arteries of the lumbar spine and cholesterol levels on patients with long-term nonspecific lower back pain. OBJECTIVES: To evaluate whether occlusion of lumbar and middle sacral arteries or serum cholesterol levels are associated with lower back pain and/or with disc degeneration. SUMMARY OF BACKGROUND DATA: Atherosclerosis in the wall of the abdominal aorta usually develops at the ostia of branching arteries and the bifurcation, and may obliterate orifices of lumbar and middle sacral arteries. Obstruction of these arteries causes ischemia in the lumbar spine and may result in back symptoms and disc degeneration. METHODS: MR aortography and cholesterol blood tests were performed on 51 patients with long-term lower back pain without specific findings (i.e., spinal or nerve root compression) in regular lumbar MR images. The patients ranged from 35 to 70 years of age (mean age, 56 years). Serum cholesterol and low-density lipoprotein (LDL) cholesterol levels were measured. To assess symptoms and disability NASS low back Outcome Instrument was used. RESULTS: Twenty-nine (78%) of 37 men and 11 (77%) of 14 women showed occluded lumbar and/or middle sacral arteries. The prevalence of occluded arteries was 2.5 times more than in subjects of corresponding age group in a Finnish necropsy material. Twenty-three (62%) men and seven (50%) women had significant disc degeneration. Disc degeneration was associated with occluded lumbar/middle sacral arteries (P = 0.035). Patients with occluded arteries or significant disc degeneration did not complain more severe symptoms than those without, whereas patients with above normal serum LDL cholesterol scored higher in neurogenic symptoms (P = 0.031) and complained more often severe pain (P = 0.049) than those with normal LDL cholesterol. CONCLUSIONS: The study indicates that lumbar and middle sacral arteries are often occluded in patients with nonspecific long-term lower back pain. Occlusion of these arteries may also be associated with disc degeneration.", "title": "MR aortography and serum cholesterol levels in patients with long-term nonspecific lower back pain." }, { "docid": "MED-2412", "text": "OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.", "title": "Fish oil supplementation in type 2 diabetes: a quantitative systematic review." }, { "docid": "MED-4708", "text": "BACKGROUND/OBJECTIVES: Walnuts have been shown to reduce serum lipids in short-term well-controlled feeding trials. Little information exists on the effect and sustainability of walnut consumption for longer duration in a free-living situation. SUBJECTS/METHODS: A randomized crossover design in which 87 subjects with normal to moderate high plasma total cholesterol were initially assigned to a walnut-supplemented diet or habitual (control) diet for a 6-month period, then switched to the alternate dietary intervention for a second 6-month period. Each subject attended seven clinics 2 months apart. At each clinic, body weight was measured, and in five clinics (months 0, 4, 6, 10 and 12), a blood sample was collected. RESULTS: Our study showed that supplementing a habitual diet with walnuts (12% of total daily energy intake equivalent) improves the plasma lipid profile. This beneficial effect was more significant in subjects with high plasma total cholesterol at baseline. Significant changes in serum concentrations of total cholesterol (P=0.02) and triglycerides (P=0.03) were seen and nearly significant changes in low-density lipoprotein cholesterol (LDL-C) (P=0.06) were found. No significant change was detected in either high-density lipoprotein (HDL) cholesterol LDL to HDL ratio. CONCLUSIONS: Including walnuts as part of a habitual diet favorably altered the plasma lipid profile. The lipid-lowering effects of walnuts were more evident among subjects with higher lipid baseline values, precisely those people with greater need of reducing plasma total and LDL-C.", "title": "Long-term walnut supplementation without dietary advice induces favorable serum lipid changes in free-living individuals." }, { "docid": "MED-2972", "text": "BACKGROUND: Elevated levels of lipids, such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), are widely recognized as risk factors for cardiovascular disease (CVD). Oxidized LDL (OxLDL) is an emerging risk factor considered relevant in oxidative stress and endothelial dysfunction, which is implicated in the progression of CVD. Consumption of a diet rich in polyphenols may be cardioprotective through its impact on oxidative stress and protecting LDL from oxidation. OBJECTIVES: This study was designed to test the ability of strawberry phenolic compounds to mitigate the postprandial effects of a high-fat meal on OxLDL as well as investigate the effects of phenolic compounds on lipid metabolism. METHODS: Twenty-four hyperlipidemic men and women (14 women, 10 men; mean age 50.9 +/- SD 15 years) were recruited to participate in this randomized, single-blind, placebo-controlled, 12-wk crossover trial. After a 10-day run-in period, subjects consumed either an active strawberry beverage (Str; containing 10 g freeze-dried fruit) or a placebo (Pbo) beverage matched in energy and macronutrient composition for 6 weeks. Twice before randomization and once at the 6-week crossover point, subjects received either Str or Pbo with a high-fat challenge meal (HFM). TC, LDL, high-density lipoprotein cholesterol, TG, and OxLDL were measured at defined intervals for 6 h before and after HFM challenge. Fasting concentrations of blood variables at 0, 6, and 12 weeks were compared to assess chronic intake of Str or Pbo. RESULTS: After the HFM during the run-in period, TG and OxLDL were lower after Str than Pbo (p = 0.005, p = 0.01, and p = 0.0008, respectively). HFM responses after 6 weeks of Str versus Pbo resulted in decreased lipid levels and a sex by treatment interaction for OxLDL (p = < 0.0001, and p = 0.0002). CONCLUSION: The present results support a role for strawberry in mitigating fed-state oxidative stressors that may contribute to atherogenesis.", "title": "Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women." }, { "docid": "MED-5079", "text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.", "title": "Pinto bean consumption reduces biomarkers for heart disease risk." }, { "docid": "MED-1792", "text": "PURPOSE: Fruit consumption is associated with a decreased risk of CVD in cohort studies and is therefore endorsed by health authorities as part of the '5 or more a day' campaigns. A glass of fruit juice is generally counted as one serving. Fruit may cause protection by affecting common risk factors of CVD. METHODS: Apples are among the most commonly consumed fruits and were chosen for a comprehensive 5 × 4 weeks dietary crossover study to assess the effects of whole apples (550 g/day), apple pomace (22 g/day), clear and cloudy apple juices (500 ml/day), or no supplement on lipoproteins and blood pressure in a group of 23 healthy volunteers. RESULTS: The intervention significantly affected serum total and LDL-cholesterol. Trends towards a lower serum LDL-concentration were observed after whole apple (6.7%), pomace (7.9%) and cloudy juice (2.2%) intake. On the other hand, LDL-cholesterol concentrations increased by 6.9% with clear juice compared to whole apples and pomace. There was no effect on HDL-cholesterol, TAG, weight, waist-to-hip ratio, blood pressure, inflammation (hs-CRP), composition of the gut microbiota or markers of glucose metabolism (insulin, IGF1 and IGFBP3). CONCLUSIONS: Apples are rich in polyphenols and pectin, two potentially bioactive constituents; however, these constituents segregate differently during processing into juice products and clear juice is free of pectin and other cell wall components. We conclude that the fibre component is necessary for the cholesterol-lowering effect of apples in healthy humans and that clear apple juice may not be a suitable surrogate for the whole fruit in nutritional recommendations.", "title": "Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers." }, { "docid": "MED-1636", "text": "Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.", "title": "Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials." }, { "docid": "MED-1874", "text": "It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.", "title": "The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century." }, { "docid": "MED-1864", "text": "The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information. HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000 to over 5,000 mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses. There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels. Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hypolipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C. Anthocyanins found in abundance in HS calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit.", "title": "Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies" }, { "docid": "MED-1765", "text": "Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.", "title": "Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients." }, { "docid": "MED-3471", "text": "BACKGROUND: Orange juice-a rich source of vitamin C, folate, and flavonoids such as hesperidin-induces hypocholesterolemic responses in animals. OBJECTIVE: We determined whether orange juice beneficially altered blood lipids in subjects with moderate hypercholesterolemia. DESIGN: The sample consisted of 16 healthy men and 9 healthy women with elevated plasma total and LDL-cholesterol and normal plasma triacylglycerol concentrations. Participants incorporated 1, 2, or 3 cups (250 mL each) of orange juice sequentially into their diets, each dose over a period of 4 wk. This was followed by a 5-wk washout period. Plasma lipid, folate, homocyst(e)ine, and vitamin C (a compliance marker) concentrations were measured at baseline, after each treatment, and after the washout period. RESULTS: Consumption of 750 mL but not of 250 or 500 mL orange juice daily increased HDL-cholesterol concentrations by 21% (P: < 0.001), triacylglycerol concentrations by 30% (from 1.56 +/- 0.72 to 2.03 +/- 0.91 mmol/L; P: < 0.02), and folate concentrations by 18% (P: < 0.01); decreased the LDL-HDL cholesterol ratio by 16% (P: < 0.005); and did not affect homocyst(e)ine concentrations. Plasma vitamin C concentrations increased significantly during each dietary period (2.1, 3.1, and 3.8 times, respectively). CONCLUSIONS: Orange juice (750 mL/d) improved blood lipid profiles in hypercholesterolemic subjects, confirming recommendations to consume >/=5-10 servings of fruit and vegetables daily.", "title": "HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia." }, { "docid": "MED-4550", "text": "BACKGROUND/OBJECTIVES: Vegetarian diet has become an increasing trend in western world and in Poland. The frequency of allergies is growing, and the effectiveness of vegetarian diet in allergic diseases is a concern for research. We aimed to study an effect of vegetarian diet on lipid profile in serum in a group of Polish children in Poland and to investigate lipid parameters in healthy vegetarian children and in omnivorous children with diagnosed atopic disease. SUBJECTS/METHODS: Serum lipid profiles (triglycerides, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, fatty acids) were assessed in groups of children: healthy vegetarians (n=24) and children with diagnosed atopic diseases (n=16), with control group of healthy omnivores (n=18). Diet classification was assessed by a questionnaire. RESULTS: No differences were observed in serum triglycerides, LDL cholesterol and saturated and monounsaturated fatty acids level in all groups. In the group of Polish vegetarian children, we recorded high consumption of vegetable oils rich in monounsaturated fatty acid, and sunflower oil containing linoleic acid. This observation was associated with higher content of linoleic acid in serum in this group. Among polyunsaturated n-6 fatty acids, linoleic acid revealed significantly (P<0.05) lower levels in allergy vs vegetarian groups. In case of eicosapentaenoic acid (n-3 fatty acid), the allergy group showed higher levels of this compound in comparison to vegetarians. CONCLUSIONS: Significantly higher concentration of linoleic acid in vegetarian children in comparison to allergy group indicated possible alternative path of lipid metabolism in studied groups, and in consequence, some elements of vegetarian diet may promote protection against allergy.", "title": "An impact of the diet on serum fatty acid and lipid profiles in Polish vegetarian children and children with allergy." }, { "docid": "MED-4515", "text": "BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.", "title": "The effect of a plant-based low-carbohydrate (\"Eco-Atkins\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects." }, { "docid": "MED-1327", "text": "Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48-80 g whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in post-intervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose: -0.93 mmol/L (95% CI: -1.65, -0.21), total cholesterol: -0.83 mmol/L (-1.23, -0.42); and LDL-cholesterol: -0.82 mmol/L (-1.31, -0.33)]. [corrected] Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials.", "title": "Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain." }, { "docid": "MED-5294", "text": "To determine serum lipid levels and their correlates in one of the world's most isolated populations, 62 adult Yanomamo Indians from the Amazonian rain forest were examined. After measurement of body weight and height, and estimation of age, casual blood samples were obtained. Estimated age ranged from 20 to 68 years, with men averaging 37 and women 35 years. Mean serum total cholesterol was very low among both men (123 mg/dl) and women (142 mg/dl) compared with western samples, whereas triglycerides--112 and 110 mg/dl, respectively--were lower among men and slightly higher among women than for U.S. men and women. Yanomamo women had significantly higher total cholesterol (P = 0.02) and body mass index (BMI) (P = 0.05) than men. HDL-cholesterol (P = 0.08) and LDL-cholesterol (P = 0.21) were also somewhat higher among women. Multivariate regression analysis indicated that estimated age was independently related to cholesterol in both sexes, while BMI was of borderline significance. The very low serum lipid levels in this isolated population are apparently attributable mainly to their largely vegetarian diet, low in fats and cholesterol and high in fiber, with concomitant high physical activity associated with low BMI.", "title": "Lipid profiles of Yanomamo Indians of Brazil." }, { "docid": "MED-4989", "text": "BACKGROUND: A high nutrient density (HND) vegetable-based diet offers a dietary model extremely low in saturated fat as well as refined carbohydrates and emphasizes a liberal intake of fresh fruits, vegetables, beans, and nuts. We conducted a retrospective chart review of patients who came to a family practice office seeking nutritional counseling for weight loss. All of these patients were prescribed an HND diet in an extended counseling session with a family physician. METHODS: A convenience sample (N = 56) of all patients seeking dietary counseling for weight loss from a family practice physician in a 3-year period was included in the chart review. No personal identifying data were recorded. The initial counseling sessions averaged 1 hour in length. Patients were provided with a sample HND daily meal plan and recipes and with verbal and written information about the rationale for the diet. Data recorded from patients' charts at 6-month intervals for up to 2 years of follow-up (when available) included weight, blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and cholesterol:HDL ratio. Non-parametric statistical testing using the Friedman rank order (exact) test for k-related samples was conducted. A follow-up survey on adherence and medication use was completed by 38 patients. RESULTS: Of the 33 patients who returned for follow-up after 1 year, the mean weight loss was 31 lbs (P = .000). Of the 19 patients who returned after 2 years, the mean weight loss was 53 lbs (P = .000), mean cholesterol fell by 13 points, LDL by 15 points, triglycerides by 17 points, and cardiac risk ratio dropped from 4.5 to 3.8. Changes in systolic and diastolic blood pressure were highly significant at all follow-up time intervals (P < or = .001). There was a significant correlation between adherence and degree of weight loss (P = .011). CONCLUSIONS: Weight loss was sustained in patients who returned for follow-up and was more substantial in those who reported good adherence to the recommendations. However, many patients were lost to follow-up. Favorable changes in lipid profile and blood pressure were noted. An HND diet has the potential to provide sustainable, significant, long-term weight loss and may provide substantial lowering of cardiac risk in patients who are motivated and provided with extended one-on-one counseling and follow-up visits. Development of tools to aid in patient retention is an area for possible further study. Clinical trials with long-term follow-up are needed to further test the therapeutic potential and to examine adherence and follow-up issues related to this dietary approach. An HND diet as demonstrated with this group may be the most health-favorable and effective way to lose weight for appropriately motivated patients.", "title": "Effect of a high nutrient density diet on long-term weight loss: a retrospective chart review." }, { "docid": "MED-1450", "text": "Background/objectives: To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting. Subjects/methods: Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and/or previous diagnosis of type 2 diabetes were randomized to either follow a low-fat vegan diet, with weekly group support and work cafeteria options available, or make no diet changes for 18 weeks. Dietary intake, body weight, plasma lipid concentrations, blood pressure and glycated hemoglobin (HbA1C) were determined at baseline and 18 weeks. Results: Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups, respectively (P<0.001). Total and low-density lipoprotein (LDL) cholesterol fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group (P<0.01). HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group, respectively (P<0.01). Among study completers, mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups, respectively (P<0.001). Total and LDL cholesterol fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group (P<0.001). HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group, respectively (P<0.01). Conclusions: An 18-week dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight, plasma lipids, and, in individuals with diabetes, glycemic control.", "title": "A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardiovascular risk in the corporate setting: the GEICO study" }, { "docid": "MED-1660", "text": "OBJECTIVES: Atherosclerosis of arteries supplying the lumbar region has been suggested as a mechanism leading to intervertebral disc degeneration and sciatica. The study described here examined whether serum lipid levels or pharmacologically treated hyperlipidemia were associated with sciatica. METHODS: A nationally representative sample (n=8028) of Finns aged 30 years or over was interviewed and examined. Sciatica was assessed by a physician according to preset criteria. Information for the present purpose was available for 74.8% of the sample. RESULTS: The prevalence of sciatica was 3.3% for men and 2.2% for women. In men without hyperlipidemia treatment, sciatica was associated with total cholesterol (high vs. low tertile: OR 2.28, 95% CI 1.14-4.55), LDL cholesterol (2.12; 1.11-4.05), and triglycerides (1.92; 1.04-3.55), adjusted for age, BMI, exercise, smoking, heavy physical work, and education. HDL was not associated with sciatica. For men in the highest tertile of both total cholesterol and triglycerides, the OR of sciatica was 3.89 (1.68-8.99) in comparison to men with cholesterol in the lowest tertile and triglycerides in the lowest or the middle tertile. In similar analyses among women no associations were seen. Pharmacologically treated hyperlipidemia was associated with sciatica in women (2.02; 1.01-4.04), but not in men (1.71; 0.83-3.55). CONCLUSIONS: Independent of BMI and other possible confounders, clinically assessed sciatica in men was associated with levels of atherogenic serum lipids. Pharmacologically treated hyperlipidemia was associated with sciatica in women. The findings are in accordance with the atherosclerosis-sciatica hypothesis.", "title": "Serum lipids in relation to sciatica among Finns." }, { "docid": "MED-4706", "text": "Higher nut consumption has been associated with lower risk of coronary heart disease (CHD) events in several epidemiologic studies. The study examined the association between intake of nuts and incident cardiovascular disease (CVD) in a cohort of women with type 2 diabetes. For the primary analysis, there were 6309 women with type 2 diabetes who completed a validated FFQ every 2–4 y between 1980 and 2002 and were without CVD or cancer at study entry. Major CVD events included incident myocardial infarction (MI), revascularization, and stroke. During 54,656 person-years of follow-up, there were 452 CHD events (including MI and revascularization) and 182 incident stroke cases. Frequent nut and peanut butter consumption was inversely associated with total CVD risk in age-adjusted analyses. After adjustment for conventional CVD risk factors, consumption of at least 5 servings/wk of nuts or peanut butter [serving size, 28 g (1 ounce) for nuts and 16 g (1 tablespoon) for peanut butter] was significantly associated with a lower risk of CVD (relative risk = 0.56; 95% CI: 0.36–0.89). Furthermore, when we evaluated plasma lipid and inflammatory biomarkers, we observed that increasing nut consumption was significantly associated with a more favorable plasma lipid profile, including lower LDL cholesterol, non-HDL cholesterol, total cholesterol, and apolipoprotein-B-100 concentrations. However, we did not observe significant associations for HDL cholesterol or inflammatory markers. These data suggest that frequent nut and peanut butter consumption is associated with a significantly lower CVD risk in women with type 2 diabetes.", "title": "Regular Consumption of Nuts Is Associated with a Lower Risk of Cardiovascular Disease in Women with Type 2 Diabetes" }, { "docid": "MED-3942", "text": "Background The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (Euterpe oleracea Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome. Methods This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m2 and ≤ 30 kg/m2) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment. Results Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO. Conclusion In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.", "title": "Effects of Açai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study" } ]
3412	How to account for a shared mortgage in QuickBooks Online?	[ { "docid": "543254", "text": "You could classify the mortgage as a different assets class and then create automated additions and deductions to the account as deems fit. other than that quickbooks online is a bit fishy so it seems.", "title": "" }, { "docid": "352589", "text": "What is the corporate structure? Your partnership agreement or LLC operating agreement should dictate how you approach this.", "title": "" }, { "docid": "425888", "text": "How you should record the mortgage payments depends on if you are trying to achieve correct accounting, according to the standards, or if you are just tracking everything for you and your friends. If you're just keeping track for personal reasons, I'd suggest that you set up your check (or journal entry, your preference) how you'd like it to be recorded. Then, memorize that transaction. This allows you to use it as many times as you need to, without having to set it up each time. (Also note: there is no way to record a transaction that decreases cash and increases equity.) If you're trying to keep track of everything according to accounting standards, which it should be if you've set up an official business, then you have a lot more tracking to do with each payment. Mortgage payments technically do not affect the equity accounts of the owners. Each mortgage payment should decrease the bank balance, increase interest expense and decrease the mortgage balance, not to mention tracking any escrow account you may have. The equity accounts would be affected if the owners are contributing funds to the bank account, but equity would increase at the time the funds are deposited, not when the mortgage payments are made. Hope this helps!", "title": "" } ]	[ { "docid": "479625", "text": "QuickBooks online is one of the best accounting solution choice for small business owners. So here you find how to convert QB Desktop to QB Online. IF you need more detail and help related to this visit our page- https://www.wizxpert.com/convert-your-quickbooks-desktop-file-to-quickbooks-online/", "title": "" }, { "docid": "307919", "text": "In this blog, i will share some important things about QuickBooks Online. In this busy life, Every businessman has limited time. So with the help of QuickBooks Online he/she has to keep a track record of their sales and expenses. For more - https://www.wizxpert.com/quickbooks-online-support/", "title": "" }, { "docid": "157751", "text": "A desktop application that has the same features (although as already stated, nothing will be identical but if you are looking for functionality then certainly there will be) and pretty simple to use was Microsoft Money, however, Microsoft stopped supporting it with newer versions and while the existing versions will work, I still use mine, there will be no future updates. I like the interface, its simple to use and has all the features you want. They abandoned it in favor of Intuit's Quicken but personally I am not a fan of the Quicken interface. They still had a more extensive and probably too much for the average user application called Office Accounting, but they abandoned future updates and supports on that in favor of Intuit's Quickbooks. Again, I am not a fan of the interface but they are very feature rich including invoicing and payroll, again overkill for the average user. They still have the Small Business Accounting in the form of Microsoft Dynamics, but that is utterly overkill for personal use. I generally don't trust online or cloud based accounting solutions like Mint or even Quicken online because I don't trust my information security to some third party without knowing how they are securing it and what will happen to me if/when they are leaked due to breach. So I like to keep everything local to myself and that's a good move for you, you should do that. It seems at the moment the market standard without much competition is Quicken for personal use and Quickbooks for small business. I would recommend you start with Quicken and if your needs increase in the future, you can easily transfer into Quickbooks to scale up as they are fully compatible with each other. Check it out here and compare their products to see what works best for your needs.", "title": "" }, { "docid": "78117", "text": "The company I work with uses Intuit QuickBooks Online and have had zero problems with it. The functionality is effective and it fits the size of our company as well. (Not huge, but I wouldn't consider it a 'small business') Also, you can try a 30 day free trial. QuickBooks Simple Start focuses on small business accounting, so for this reason it has a cleaner interface and is simple to use. QuickBooks Simple Start compared to Quicken Home This article doesn't exactly have a bright light shining on Quickbooks, but I think it's fair to show you other alternatives: http://www.pcmag.com/article2/0,2817,2382514,00.asp [Note that it is from 2011]", "title": "" }, { "docid": "24890", "text": "\"Since this is a cooperative I'm guessing your partners may want to be able to view the books so another key point you may want to consider is collaboration. QuickBooks desktop has all of these same issues because it is meant to be used on a single desktop. We're in an age of mobile devices, and especially in a business like landscaping it would be nice if certain aspects of record keeping could be done at the point and time where they are incurred. I'd argue you want a Software as a Service (SaaS) accounting package as opposed to \"\"accounting software\"\" which might come on a CD in the form of QuickBooks, Sage and others. Additionally, most of these will also have guides to help make sure you are properly entering your records. Most of these SaaS products also have customer success teams to help you along should you need assistance. Depending on the level of your subscription you may get more sophisticated handling of taxes, customized invoices or integrated payroll. Your goal is to keep accurate records so you can better run your business and maintain obligations like filing taxes. You're not keeping the records just to have them. Keep them in a place where they will work for you and provide the insights and functionality that will help your business grow and become successful. Accounting software will always win in this scenario over a spreadsheet. FULL DISCLAIMER: I work for Kashoo, a simple cloud accounting product designed for small businesses. But the points I mention above are true for Xero, QuickBooks Online and Wave as well as Kashoo. And if you really want expertise to go with the actual software consider service providers with a platform like: Indinero, Bench, easyrecordbooks or Liberty Accounting.\"", "title": "" }, { "docid": "505361", "text": "I use QuickBooks online... It's really the best out there for the price, just make sure to never upgrade to an edition you aren't 100% sure you need or you're forever stuck essentially. That's the mess I'm in right now. Paying $20 more than necessary a month, but it's still cheaper than switching to, say, xero. The starter edition of QuickBooks online is a lot more powerful than the equivalent plans anywhere else for the price.", "title": "" }, { "docid": "112728", "text": "Any accounting software should be able to handle this. When you invoice them, set the invoice date to the date of the event. Then receive a partial payment against that invoice. This will cause your accounting software to display the service income in the correct period as well. So if you sent them invoice for August 7, 2014 event on May 5th, 2014 and they gave you $500 due, you would see this Income in August ($500 on Cash basis, $1000 on Accrual basis. When you received the other $500 in August, you would see $1000 for both methods). You would not see any income in May, when you created the invoice. This is better for revenue matching with the correct period. When you send them same invoice (say 30 days before the event), Set the software to show payments already received (it seems that most online accounting software will do this by default). Here is an example in Freshbooks. Here is an example in Xero: Seems they both display information on when you can expect payment on the their respective dashboards. In the Desktop version of Quickbooks (which I use a lot), it will not show the balance of the customer by default on an invoice. You will have to modify the invoice template. There are more details on that here. In Desktop version of Quickbooks, you can look at Cash Flow Forecast report to see the expected amount coming in. I hope that helps and good luck.", "title": "" }, { "docid": "224438", "text": "for starters get a cheap easy accounting software pack like quickbooks and have the salesmen train you on it's use and set-up. the 50k you put into the company will count as paid up share capital. then any future withdrawal from company account will show as loan to director.", "title": "" }, { "docid": "102002", "text": "Is it normal in QuickBooks to have credit card expenses being shows as liabilities? Is there a way I can correct this? If they are expenses they shouldn't be negative liabilities unless you overpaid your credit card by that amount. It sounds like perhaps when you linked the account the credit/debit mapping may have been mixed up. I've not used QB Online, but it looks like you might have to un-link the account, move all the existing transactions to 'excluded' and then link the account again and flip-flop the debit/credit mapping from what it is now. Hopefully there's an easier way. This QB community thread seems to address the same issue.", "title": "" }, { "docid": "291726", "text": "Visit QuickBooks Support help desk to fix issues online. You can face any types of issues in your software but overlooking those issues is not a good idea. Payroll and POS related issues can also be fixed at the same point of time. Give a call on QuickBooks support number 1-800-290-0629. Visit the website http://www.quick-books-support.com to get all kind of help.", "title": "" }, { "docid": "263499", "text": "A special 24/7 available QuickBooks support phone number helpline for users who are getting any issues or trouble or errors. You are just one call away to get world class QuickBooks customer support service. Dial or call today to know exactly how we can help you. visit our page - https://events.com/r/en_US/registration/quickbooks-customer-support-phone-number-1855-441-4417-los-angeles-june-62185", "title": "" }, { "docid": "203446", "text": "\"If you are using software like QuickBooks (or even just using spreadsheets or tracking this without software) use two Equity accounts, something like \"\"Capital Contributions\"\" and \"\"Capital Distributions\"\" When you write a personal check to the company, the money goes into the company's checking account and also increases the Capital Contribution account in accordance with double-entry accounting practices. When the company has enough retained earnings to pay you back, you use the Capital Distributions equity account and just write yourself a check. You can also make general journal entries every year to zero out or balance your two capital accounts with Retained Earnings, which (I think) is an automatically generated Equity account in QuickBooks. If this sounds too complex, you could also just use a single \"\"Capital Contributions and Distributions\"\" equity account for your contributions and distributions.\"", "title": "" }, { "docid": "320853", "text": "In this artice we are trying to show you what is QuickBooks Payroll Error PS032 and how to resolve it. For a technical help about this you can contact us at - https://www.wizxpert.com/quickbooks-payroll-customer-service/ or dial our helpline number +1 855 441 4417.", "title": "" }, { "docid": "495242", "text": "In this artice we are trying to show you what is QuickBooks Payroll Error 30159 and how to resolve it. For a technical help about this you can contact us at - https://www.wizxpert.com/quickbooks-payroll-customer-service/ or dial our helpline number +1 855 441 4417.", "title": "" }, { "docid": "254431", "text": "You can do this through a journal entry in Quickbooks. It can all be entered as one entry, there's no need to do separate ones for each bill. The journal entry should debit Accounts Payable and credit your equity account. In the line for Accounts Payable, make sure to choose your name in the 'Name' column. This, in effect, enters a credit to your account, which will offset the bills that were shown there previously. The last step is to apply those credits to the bills. Even though they offset each other, your name would still show up in any Payables reports and in the Pay Bills window. To do this, open the Pay Bills window and select one of the bills owed to you. There should be an option to choose 'Apply Credits' or something similar (depends on which version of Quickbooks you are running). Choose that option, and apply credits in the amount of the bill, so that it zeroes out. Do the same for all of the other bills. Once they are all checked off, click the button to Pay Bills. This won't actually 'pay' anything, but will instead just apply the credits to the bills as indicated.", "title": "" }, { "docid": "425672", "text": "I use online banking and bill pay for all accounts where I can control when and how much is paid, where I push the funds out. The bills from those companies that want to be allowed to reach into my account and pull money automatically (e.g. my Chase mortgage) I simply will not enroll - they get a paper check in the mail. There is no way I am giving these cocksucker criminals permission to take money out of my accounts.", "title": "" }, { "docid": "391668", "text": "A company would have significantly less capital to pay a skilled worker at that point though. Keep that in mind. So, to circle back now. Small businesses make up a decent amount of our GDP and job creation. Let's say you have had it working fir someone else and want to strike out on your own. You decide to start an e-commerce site, reselling from a factory on amazon. Simple enough set up. Online marketing made simple through amazon, google and facebook. But you don't have any idea how to translate that info into QuickBooks and push out the financial info needed for taxes, payroll, etc. You need to hire a bookkeeper to sort it out, but it os only 5 hours worth of work per week. Do you hire them as a salaried employee giving them a liveable wage or pay them the rate you agreed upon for those 5 hours?", "title": "" }, { "docid": "321637", "text": "\"If you need less than $125k for the downpayment, I recommend you convert your mutual fund shares to their ETF counterparts tax-free: Can I convert conventional Vanguard mutual fund shares to Vanguard ETFs? Shareholders of Vanguard stock index funds that offer Vanguard ETFs may convert their conventional shares to Vanguard ETFs of the same fund. This conversion is generally tax-free, although some brokerage firms may be unable to convert fractional shares, which could result in a modest taxable gain. (Four of our bond ETFs—Total Bond Market, Short-Term Bond, Intermediate-Term Bond, and Long-Term Bond—do not allow the conversion of bond index fund shares to bond ETF shares of the same fund; the other eight Vanguard bond ETFs allow conversions.) There is no fee for Vanguard Brokerage clients to convert conventional shares to Vanguard ETFs of the same fund. Other brokerage providers may charge a fee for this service. For more information, contact your brokerage firm, or call 866-499-8473. Once you convert from conventional shares to Vanguard ETFs, you cannot convert back to conventional shares. Also, conventional shares held through a 401(k) account cannot be converted to Vanguard ETFs. https://personal.vanguard.com/us/content/Funds/FundsVIPERWhatAreVIPERSharesJSP.jsp Withdraw the money you need as a margin loan, buy the house, get a second mortgage of $125k, take the proceeds from the second mortgage and pay back the margin loan. Even if you have short term credit funds, it'd still be wiser to lever up the house completely as long as you're not overpaying or in a bubble area, considering your ample personal investments and the combined rate of return of the house and the funds exceeding the mortgage interest rate. Also, mortgage interest is tax deductible while margin interest isn't, pushing the net return even higher. $125k Generally, I recommend this figure to you because the biggest S&P collapse since the recession took off about 50% from the top. If you borrow $125k on margin, and the total value of the funds drop 50%, you shouldn't suffer margin calls. I assumed that you were more or less invested in the S&P on average (as most modern \"\"asset allocations\"\" basically recommend a back-door S&P as a mix of credit assets, managed futures, and small caps average the S&P). Second mortgage Yes, you will have two loans that you're paying interest on. You've traded having less invested in securities & a capital gains tax bill for more liabilities, interest payments, interest deductions, more invested in securities, a higher combined rate of return. If you have $500k set aside in securities and want $500k in real estate, this is more than safe for you as you will most likely have a combined rate of return of ~5% on $500k with interest on $500k at ~3.5%. If you're in small cap value, you'll probably be grossing ~15% on $500k. You definitely need to secure your labor income with supplementary insurance. Start a new question if you need a model for that. Secure real estate with securities A local bank would be more likely to do this than a major one, but if you secure the house with the investment account with special provisions like giving them copies of your monthly statements, etc, you might even get a lower rate on your mortgage considering how over-secured the loan would be. You might even be able to wrap it up without a down payment in one loan if it's still legal. Mortgage regulations have changed a lot since the housing crash.\"", "title": "" }, { "docid": "522798", "text": "There are 2 main types of brokers, full service and online (or discount). Basically the full service can provide you with advice in the form of recommendations on what to buy and sell and when, you call them up when you want to put an order in and the commissions are usually higher. Whilst an online broker usually doesn't provide advice (unless you ask for it at a specified fee), you place your orders online through the brokers website or trading platform and the commissions are usually much lower. The best thing to do when starting off is to go to your country's stock exchange, for example, The ASX in Sydney Australia, and they should have a list of available brokers. Some of the online brokers may have a practice or simulation account you can practice on, and they usually provide good educational material to help you get started. If you went with an online broker and wanted to buy Facebook on the secondary market (that is on the stock exchange after the IPO closes), you would log onto your brokers website or platform and go to the orders section. You would place a new order to buy say 100 Facebook shares at a certain price. You can use a market order, meaning the order will be immediately executed at the current market price and you will own the shares, or a limit price order where you select a price below the current market price and wait for the price to come down and hit your limit price before your order is executed and you get your shares. There are other types of orders available with different brokers which you will learn about when you log onto their website. You also need to be careful that you have the funds available to pay for the share at settlement, which is 3 business days after your order was executed. Some brokers may require you to have the funds deposited into an account which is linked to your trading account with them. To sell your shares you do the same thing, except this time you choose a sell order instead of a buy order. It becomes quite simple once you have done it a couple of times. The best thing is to do some research and get started. Good Luck.", "title": "" }, { "docid": "97962", "text": "There are 2 basic ways to have someone buy partial ownership of your company: OR If they buy shares that you already own, then their shares will have the same rights as yours (same voting rights, same dividend rights, etc.). If they buy shares newly created from the company, they could be either identical shares to what you already own, or they could be a new class of shares [you may need to adjust the articles of incorporation if you did not plan ahead with multiple share classes]. You really need to talk to a lawyer & tax accountant about this. There are a lot of questions you need to consider here. For example: do you want to use the money in the business, or would you rather have it personally? Are you concerned about losing some control of how the business is run? What are the short term and long-term tax consequences of each method? What does your new partner want in terms of their share class? The answers to these questions will be highly valuable, and likely worth much more than the fees you will need to pay. At the very least, you will likely need a lawyer and accountant anyway to ensure the filings & taxes are done correctly, so better to involve them now, rather than later. There are many other situations to consider here, and an online forum is not the best place to get advice that might put you in a sticky legal situation later on.", "title": "" }, { "docid": "45174", "text": "Here's a good strategy: Open up a Roth IRA at a discount-broker, like TD Ameritrade, invest in no-fee ETF's, tracking an Index, with very low expense ratios (look for around .15%) This way, you won't pay brokers fees whenever you buy shares, and shares are cheap enough to buy casually. This is a good way to start. When you learn more about the market, you can check out individual stocks, exploring different market sectors, etc. But you won't regret starting with a good index fund. Also, it's easy to know how well you did. Just listen on the radio or online for how the Dow or S&P did that day/month/year. Your account will mirror these changes!", "title": "" }, { "docid": "459423", "text": "\"I can just get the exact same mortgage in a 30-year version, and just pay it off within whatever year window I choose This is an assumption which often does not come true. The \"\"advantage\"\" of a 15 year mortgage is you hopefully never decide you want more toys or to go out to eat and suddenly your mortgage takes 30 years to pay off instead of 15. Plus, if I get a 30-year mortgage then I have a cushion in case I run into major financial hardship. That same cushion can turn into other luxuries. Maybe you want new furniture. \"\"I won't pay extra on the mortgage this year.\"\" Suddenly it's year 22. This is not a 100% guarantee by any means, but it is something which is relatively likely. Yet everywhere I look I see people online going on about how unwise 30-year mortgages are I read a lot of online financial resources and almost never see this claim.\"", "title": "" }, { "docid": "30142", "text": "I think your reasons are good. Fundamentally accounting software is built to ensure you record your accounting data effectively with minimal mistakes and good auditing. But you still need to use the tool properly to get the benefit. One other advantage is that many accountants are familiar with, say QuickBooks, and can do your accounts more effectively if you use their preferred tool.", "title": "" }, { "docid": "329774", "text": "Business bookkeeping services helps small businesses in all aspect of managing their accounts and financial data within the accounting software. We have expertise in following accounting software QuickBooks, MYOB, and Peachtree. We have also used other small business accounting software like Great plain, Simply Accounting, etc. Using this software we can produce various reports, graphs, and other analysis documents to help you in your bookkeeping tasks.", "title": "" }, { "docid": "75235", "text": "The ownership of the house depends on what the original deed transferring title at the time of purchase says and how this ownership is listed in government records where the title transfer deed is registered. Hopefully the two records are consistent. In legal systems that descended from British common law (including the US), the two most common forms of ownership are tenancy in common meaning that, unless otherwise specified in the title deed, each of the owners has an equal share in the entire property, and can sell or bequeath his/her share without requiring the approval of the others, and joint tenancy with right of survivorship meaning that all owners have equal share, and if one owner dies, the survivors form a new JTWROS. Spouses generally own property, especially the home, in a special kind of JTWROS called tenancy by the entirety. On the other hand, the rule is that unless explicitly specified otherwise, tenancy in common with equal shares is how the owners hold the property. Other countries may have different default assumptions, and/or have multiple other forms of ownership (see e.g. here for the intricate rules applicable in India). Mortgages are a different issue. Most mortgages state that the mortgagees are jointly and severally liable for the mortgage payments meaning that the mortgage holder does not care who makes the payment but only that the mortgage payment is made in full. If one owner refuses to pay his share, the others cannot send in their shares of the mortgage payment due and tell the bank to sue the recalcitrant co-owner for his share of the payment: everybody is liable (and can be sued) for the unpaid amount, and if the bank forecloses, everybody's share in the property is seized, not just the share owned by the recalcitrant person. It is, of course, possible to for different co-owners to have separate mortgages for their individual shares, but the legalities (including questions such as whose lien is primary and whose secondary) are complicated. With regard to who paid what over the years of ownership, it does not matter as far as the ownership is concerned. If it is a tenancy in common with equal shares, the fact that the various owners paid the bills (mortgage payments, property taxes, repairs and maintenance) in unequal amounts does not change the ownership of the property unless a new deed is recorded with the new percentages. Now, the co-owners may decide among themselves as a matter of fairness that any money realized from a sale of the property should be divided up in accordance with the proportion that each contributed during the ownership, but that is a different issue. If I were a buyer of property titled as tenancy in common, I (or the bank who is lending me money to make the purchase) would issue separate checks to each co-seller in proportion to the percentages listed on the deed of ownership, and let them worry about whether they should transfer money among themselves to make it equitable. (Careful here! Gift taxes might well be due if large sums of money change hands).", "title": "" }, { "docid": "143329", "text": "QuickBooks enterprise provide audit trail for recover the details of the deleted transaction so that you can re-create the transaction. The audit trail is only capturing information related to new, deleted, and modified transactions. If you are unable to locate the delete transaction contact QuickBooks Enterprise site - https://www.wizxpert.com/quickbooks-enterprise-support/", "title": "" }, { "docid": "456885", "text": "\"I really wish someone would release a similar product to quickbooks, its so SLOW and clunky. Its my number 1 question from my small business IT clients... \"\"is there anything out there besides quickbooks?\"\" I hear freshbooks is good, but everyone is so ingrained in the quickbooks way of doing things it would be a strugle to switch people to a different product.\"", "title": "" }, { "docid": "539418", "text": "I have done this last year. Just open an account with an online brocker and buy a couple of Apple shares (6 I think, for 190$ each or something like that :) ). If this is just to test how stock exchange works, I think this is a good idea. I am also in Europe (France), and you'r right the charge to buy on NasDaq are quite expensive but still reasonnable. Hope this helps.", "title": "" }, { "docid": "71987", "text": "\"For anyone that's curious, I had a number of chats with Quickbooks who recommended I import only the relevant business transactions from my personal account & personal credit card in order to lower the tax liability. This way money \"\"paid\"\" from the business account to myself rightly shows up as a transfer and not as income. This means when generating a tax report, it calculates the correct rate of tax to be paid based on income minus allowable expenses, regardless which account they came from.\"", "title": "" }, { "docid": "36251", "text": "\"To Many question and they are all treated differently. I was wondering how the logistics of interest and dividend payments are handled on assets , such as mortgages, bonds, stocks, What if the owner is some high-frequency algorithm that buys and sells bonds and stocks in fractions of a second? When the company decides to pay dividends, does it literally track down every single owner of that stock and deposit x cents per share in that person's bank account? (This sounds absolutely absurd and seems like it would be a logistical nightmare). In Stocks, the dividends are issued periodically. The dividend date is declared well in advance. As on end of the day on Dividend date, the list of individuals [or entities] who own the stock is available with the Stock-Exchange / Registrar of the companies. To this list the dividends are credited in next few days / weeks via banking channel. Most of this is automated. What if the owner is some high-frequency algorithm that buys and sells bonds and stocks in fractions of a second? On bonds, things work slightly differently. An Bond is initially issued for say 95 [discount of 5%] and payment of 100 after say 5 years. So when the person sells it after an year, he would logically look to get a price of 96. Of course there are other factors that could fetch him a price of 94.50 or 95.50. So every change in ownership factors in the logical rate of interest. The person who submits in on maturity gets 100. For the homeowner, I'm assuming he / she still makes mortgage payments to the initial bank they got the mortgage from, even if the bank no longer \"\"owns\"\" the mortgage. In this case, does the trader on the secondary market who owns the mortgage also come back to that bank to collect his interest payment? This depends on how the original financial institution sells the mortgage to new institutions. Generally the homeowner would keep paying initial financial institution and they would then take a margin and pay the secondary investor. If this was collateral-ized as Mortgage backed security, it is a very different story.\"", "title": "" } ]
5a81d01f55429903bc27b9c6	The Facts Behind the Helsinki Roccamatios only received acclaim after which other 2001 Yann Martel novel was released?	[ { "docid": "1953267", "text": "The Facts Behind the Helsinki Roccamatios and Other Stories is a book of short stories by Canadian author Yann Martel. First published as a paperback by Knopf Canada in the spring of 1993, it received little attention outside Canada until 2004, after Martel's award-winning \"Life of Pi\" gained worldwide popularity and people became interested in the author's work.", "title": "" }, { "docid": "419078", "text": "Life of Pi is a Canadian fantasy adventure novel by Yann Martel published in 2001. The protagonist is Piscine Molitor \"Pi\" Patel, an Indian boy from Pondicherry who explores issues of spirituality and practicality from an early age. He survives 227 days after a shipwreck while stranded on a lifeboat in the Pacific Ocean with a Bengal tiger named Richard Parker.", "title": "" } ]	[ { "docid": "38330062", "text": "\"Life of Pi\" is a 2012 American 3D adventure drama film based on Yann Martel's 2001 novel of the same name. Directed by Ang Lee, the film is based on an adapted screenplay by David Magee, and stars Suraj Sharma, Irrfan Khan, Gérard Depardieu, Tabu, and Adil Hussain.", "title": "" }, { "docid": "51089708", "text": "The High Mountains of Portugal is a 2016 novel by Canadian author Yann Martel. The novel is split into three sections, each of which concerns a widower.", "title": "" }, { "docid": "45458714", "text": "Yann Demange (born in 1977) is a French film director. After directing the well-received television series \"Dead Set\" (2008) and \"Top Boy\" (2011), he made his directorial film debut with the critically acclaimed independent film \"'71\" (2014), for which he received the British Independent Film Award for Best Director.", "title": "" }, { "docid": "25706924", "text": "Yann Martel (born 25 June 1963) is a Spanish-born Canadian author best known for the Man Booker Prize-winning novel \"Life of Pi\", a #1 international bestseller published in more than 50 territories. It has sold more than 12 million copies worldwide and spent more than a year on the Bestseller Lists of the \"New York Times\" and \"The Globe and Mail\", among many other bestseller lists. It was adapted to the screen and directed by Ang Lee, garnering four Oscars (the most for the event) including Best Director and won the Golden Globe Award for Best Original Score.", "title": "" }, { "docid": "2249628", "text": "Self is a novel by Yann Martel. It tells the story of a traveling writer who wakes up one morning to discover that he has become a woman. It was first published by Knopf Canada in 1996.", "title": "" }, { "docid": "27175664", "text": "Beatrice and Virgil is Canadian writer Yann Martel's third novel. First published in April 2010, it contains an allegorical tale about representations of the Holocaust. It tells the story of Henry, a novelist, who receives the manuscript of a play in a letter from a reader. Intrigued, Henry traces the letter to a taxidermist, who introduces him to the play's protagonists, two taxidermy animals—Beatrice, a donkey, and Virgil, a monkey.", "title": "" }, { "docid": "42255328", "text": "Hossein Abedini is an Iranian actor. His debut film was \"Pedar\" (Father), which was released in 1996 and directed by Majid Majidi. He received critical acclaim after portraying Lateef, a 17-year-old native Iranian boy in the 2001 film \"Baran\", which was also directed by Majid Majidi. His other films include \"Rasm-e ashegh-koshi\" (Tradition of lover killing) in 2004, \"Wind Blows in the Meadow\" (2009) and \"Rouyidan Dar Bad\" (Growing in the wind) in 2012.", "title": "" }, { "docid": "30952655", "text": "Life of Pi is a 2012 American survival drama film based on Yann Martel's 2001 novel of the same name. Directed by Ang Lee, the film's adapted screenplay was written by David Magee, and it stars Suraj Sharma, Irrfan Khan, Rafe Spall, Tabu, Adil Hussain, and Gérard Depardieu. The storyline revolves around an Indian man named \"Pi\" Patel, telling a novelist about his life story, and how at 16 he survives a shipwreck in which his family dies, and is adrift in the Pacific Ocean on a lifeboat with a Bengal tiger. The film had its worldwide premiere as the opening film of the 51st New York Film Festival at both the Walter Reade Theater and Alice Tully Hall in New York City on September 28, 2012.", "title": "" }, { "docid": "6834783", "text": "Pyramid Electric Co. is the first full-length solo album by Jason Molina, released in 2004 on Secretly Canadian Records. It was recorded by Mike Mogis and received universal critical acclaim according to Metacritic (with an 81 aggregate score). While critics found it hard going: \"Pyramid is not but the musical equivalent of A Season in Hell, not something one can take in often, but which is beautiful for the fact that it was completed at all\", they also commented on the sincerity of the delivery: \"The delivery is too matter-of-fact, too genuine to evoke pity or sadness. It is lethargic, yet not dreary — it grabs you violently and lays you down so, so gently.\" An unusual feature of the album was that it was released as a vinyl LP only, but each copy also contains the CD version of the album in miniaturized artwork.", "title": "" }, { "docid": "4440271", "text": "Cruel Melody is the debut album of American rock band Black Light Burns, released on June 5, 2007, through Ross Robinson's label I AM: WOLFPACK. The album is an outcome of frontman Wes Borland's efforts after his departure from Limp Bizkit in 2001, after which he took part in many projects such as Eat the Day and The Damning Well. After receiving additional inputs from then members Danny Lohner, Josh Freese and Josh Eustis, \"Cruel Melody\" was released in the spring of 2007 to critical acclaim.", "title": "" }, { "docid": "17246047", "text": "\"Battleship Grey\" is a song by Tiësto with Kirsty Hawkshaw providing vocals. It appeared on his first album, \"In My Memory\". It was also included on Hawkshaw's album, \"Meta Message\". Miro or Miromusic created a chillout remix which received great acclaim, and led to the release of the single. Only 300 copies were released through Nebula Records, and 100 in other labels.", "title": "" }, { "docid": "10045292", "text": "Cristina García (born July 4, 1958) is a Cuban-born American journalist and novelist. After working for \"Time Magazine\" as a researcher, reporter, and Miami bureau chief, she turned to writing fiction. Her first novel, \"Dreaming in Cuban\" (1992), received critical acclaim and was a finalist for the National Book Award. She has since published her novels \"The Agüero Sisters\" (1997) and \"Monkey Hunting\" (2003), and has edited books of Cuban and other Latin American literature. Her fourth novel, \"A Handbook to Luck\", was released in hardcover in 2007 and came out in paperback in April 2008.", "title": "" }, { "docid": "47706366", "text": "Karisiriyaana or Karisiriyana is a history based thriller novel authored by Dr. K. N. Ganeshaiah. The title 'Karisiriyaana' is a portmanteau of three Kannada words, 'kari', 'siri', and 'yaana', which respectively mean 'elephant', 'wealth' and 'journey'. The novel has a story based on the legend which claims that the huge wealth in the Vijayanagara kingdom was moved to a secret location soon after the death of its last king, on several hundred elephants. There was a three day gap between the last day of the last battle of Vijayanagara empire and the beginning of the looting of the precious gems and gold the king had possessed by the rival Muslim kings. In those three days, a large chunk of the wealth got mysteriously disappeared. The hunt for this treasure is the plotline of the novel. To add more mystery, the novel uses several historical facts related to Vijayanagara Dynasty. Characters in the novel explore the details surrounding this empire and related wealth. The novel has the description of rise of the empire and the reasons behind it, also how others captured the wealth. Kings interaction with Tirupati Venkateswara temple, and a brief history of the temple is described. This book has many facts with listed references suitable for students and researchers along with general readers.", "title": "" }, { "docid": "2527567", "text": "The Last King of Scotland is a 1998 novel by journalist Giles Foden. Focusing on the rise of Ugandan President Idi Amin and his reign as dictator from 1971 to 1979, the novel is written as the memoir of a fictional Scottish doctor in Amin's employ. Giles Foden's novel received critical acclaim and numerous awards when it was published by Faber and Faber in 1998. It interweaves fiction and historical fact. In 2006 a film by the same name was produced based on the novel.", "title": "" }, { "docid": "25924335", "text": "The Other Face of Janus is a 2001 young adult novel by Louise Katz. It follows the story of Edwina Nearly who after facing a range of problems decides to get away from it all by visiting an art gallery only to fall into a painting in which laws of physics don't apply.", "title": "" }, { "docid": "7794026", "text": "\"Candy\" is a song by Ash, released as the fourth single from their album \"Free All Angels\" on October 1, 2001. It was released as a single CD (released on 2CD formats, the first of which being an enhanced CD) as a 7\" vinyl (which was limited edition and came with a numbered picture gatefold sleeve), as well as on DVD format. Although Candy did only slightly better than previous single \"Sometimes\" (reaching #20), it was considered a success due to it being released a large period after the album, and the fact it helped sell many copies of the said album.", "title": "" }, { "docid": "3317531", "text": "The United States of America is a 1968 album by The United States of America. Produced by David Rubinson, it was released by Columbia Records in 1968. The album was the only release by The United States of America when they were still together and received positive reviews on its release, charting at 181 on the \"Billboard\" 200. The album has been re-issued several times and continues to receive critical acclaim decades after its original release.", "title": "" }, { "docid": "36305636", "text": "The Better Angels is a 1979 thriller novel by Charles McCarry. It was poorly received at the time of its release, citing the premise of terrorists using passenger planes as instruments of destruction too implausible to suspend one's disbelief. It was the basis of the comedic 1982 Richard Brooks film \"Wrong Is Right\" starring Sean Connery, which was similarly poorly received. In 2008, the book, along with other McCarry thrillers, was released by Overlook Duckworth Press, labeled \"the prophetic thriller.\" It is now believed to have predicted the attacks of September 11, 2001, and its aftermath. The title is a reference to Abraham Lincoln's first inaugural address, a quote from which is the novel's epigraph, and the term is said to refer to Patrick Graham's conception of President Lockwood and Julian Hubbard.", "title": "" }, { "docid": "18802372", "text": "Four0ninE is the first EP by Canadian grindcore band Fuck the Facts. It was recorded in mid May 2001 by the band. It marks the first recordings with vocalist Brent Christoff, and the only recordings with bassist Shomir Das. It is the second release by Fuck the Facts as a band, the first being a split with Ames Sanglates. Days after the recording of this EP, Shomir left the band.", "title": "" }, { "docid": "23500668", "text": "The Helsinki Prison, also known as Sörnäinen Prison (earlier known as Helsinki Central Prison) is a prison located in the Kalasatama district of Helsinki, Finland, opened in 1881. All persons placed in the prison have received a sentence of at least a year. At the moment it is the only prison operating in Helsinki proper after the Katajanokka prison was converted to a hotel and its inmates transferred to a new prison in Vantaa, a suburban municipality.", "title": "" }, { "docid": "5613706", "text": "In Ancient Roman civil law, acceptilatio is defined to be a release by mutual interrogation between debtor and creditor, by which each party is exonerated from the same contract. In other words, acceptilatio is the form of words by which a creditor releases his debtor from a debt or obligation, and acknowledges he has received that which in fact he has not received (\"veluti imaginaria solutio\"). It is equivalent to the modern acceptilation.", "title": "" }, { "docid": "16752996", "text": "What a Lemon is an album by Danish rock band Gasolin', released 1 August 1976 on Epic Records in the United States, some parts of Europe, Japan and Australia. It is the third of four albums with English lyrics that Gasolin' released between 1974 and 1978 in an attempt to break the international music market. The album received good reviews from leading American rock critics, but lack of airplay and the fact that the record company invested only small efforts in promotion and distribution meant that it never earned the band the public acclaim it was striving for.", "title": "" }, { "docid": "11177345", "text": "One Step Behind is a 1997 crime novel by Swedish author Henning Mankell, the seventh in his acclaimed Inspector Wallander series.", "title": "" }, { "docid": "25588237", "text": "Mai-HiME: Unmei no Keitouju (舞-HiME 運命の系統樹, \"Mai-HiME: The Genealogical Tree of Fate\") is a visual novel published by Sunrise Interactive. Only weeks after Sunrise's \"My-HiME\" anime series started airing in Japan, a game of the series was already announced. Marvelous Interactive is behind this game for PlayStation 2. A PC version named \"Mai-HiME: Unmei no Keitouju - Shura\" was released on June 30, 2006 by CIRCUS. The adventure game is set in the Kazehana Gakuen, which is protected by the \"Hime\" of the title. The Tree of Fate in the title points to the fact that the game provides a different view and perspective in the Mai-Hime world than that of the anime series. Character designs are not the same as the ones in the anime series. The game also features an ending different from the anime series.", "title": "" }, { "docid": "17099276", "text": "The Moment is the sixth album by British singer Lisa Stansfield, released by ZTT Records on 27 September 2004. It was her first new studio album since 2001's \"Face Up\". \"The Moment\" was entirely produced by Trevor Horn, the acclaimed producer behind Frankie Goes to Hollywood and Seal. It garnered positive reviews from music critics who praised Stansfield's voice and the fact that an established artist like her is still evolving and experimenting. \"The Moment\" was released in the United Kingdom and Japan in September 2004 and in Europe in February 2005, and performed moderately on the charts. Two main singles released from the album include \"Treat Me Like a Woman\" and \"If I Hadn't Got You\". On 6 April 2015, \"The Moment \" was re-released with five bonus tracks, three previously unreleased.", "title": "" }, { "docid": "39683007", "text": "The Leftovers is a 2011 novel by American author Tom Perrotta chronicling life on earth after a rapture-like event takes some and leaves others behind. The billions left behind are all touched by the loss of loved ones in the \"Sudden Departure,\" compounded by the significant social and philosophical concerns and implications of what it means to be left behind, when others were chosen.", "title": "" }, { "docid": "33294820", "text": "Kingdom Under Fire: A War of Heroes (also known as simply Kingdom Under Fire) is a real-time strategy video game developed by Phantagram and published by Gathering of Developers. Released for Windows in 2001, the game is based in a high fantasy setting and is played from an overhead isometric perspective. The game included single-player and multiplayer online modes through Phantagram's \"\"Wargate\"\" server. The game is the first release in the \"Kingdom Under Fire\" series, which later received critical acclaim through the Xbox release \"\", a game which, like others in the series, incorporated both role-playing and real-time strategy elements. A \"Gold Patch\" was released for \"Kingdom Under Fire\" which introduced a map editor, extra missions, and in-game save option; this version was also re-released as Kingdom Under Fire Gold.", "title": "" }, { "docid": "459256", "text": "Franka Potente (born 22 July 1974) is a German actress and singer. She first appeared in the comedy \"After Five in the Forest Primeval\" (1995), for which she won a Bavarian Film Award for Best Young Actress. Her breakthrough came in 1998, when she had the leading role in the acclaimed action thriller \"Lola rennt\" (released in English as \"Run Lola Run\"). Potente received Germany's highest acting awards for her performances in \"Run Lola Run\" and the television film \"Opernball\" (also 1998), and after half a decade of well-received roles in German productions, she made the transition to Hollywood in \"Blow\" (2001) and the first two \"Bourne\" films (2002–2004).", "title": "" }, { "docid": "41506949", "text": "The Narrow Road to the Deep North is the sixth novel by Richard Flanagan. It received critical acclaim on its release, and won the 2014 Man Booker Prize.", "title": "" }, { "docid": "11462123", "text": "Amiya Bhushan Majumdar (March 22, 1918 – July 8, 2001) was an acclaimed Indian novelist, short-story writer, essayist and playwright. In a writing career spanning over four decades, Majumdar wrote numerous novels, short stories, plays and essays in Bengali. Known as the ‘Writer’s Writer’, Majumdar is considered one of the most noteworthy authors of modern Bengali prose. His works received significant critical acclaim and recognition – including the Sahitya Academi Award for his novel Rajnagar in 1986", "title": "" } ]
1673	Do I have to pay taxes on income from my website or profits?	[ { "docid": "124505", "text": "Being a tax professional, my understanding is that the threshold limit is a single limit for all your source(s) of income. Now many people who already draw salary which is liable to tax, develop application for mobile and generate some income. Such income is liable to tax, if along with other income they exceed the threshold limit. Income will have surely related expenses. And the expenses which are related to earning of the income are allowed to be deducted.", "title": "" }, { "docid": "374264", "text": "I am not an accountant, but I do run a business in the UK and my understanding is that it's a threshold thing, which I believe is £2,500. Assuming you don't currently have to submit self assessment, and your additional income from all sources other than employment (for which you already pay tax) is less than £2,500, you don't have to declare it. Above this level you have to submit self assessment. More information can be found here I also find that HMRC are quite helpful - give them a call and ask.", "title": "" }, { "docid": "445548", "text": "\"Income is income... it depends how it's structured.. personal or corporate.. but still you need to pay taxes... if you get audited, the tax man could look at your bank statements and ask, \"\"where is this money coming from\"\"\"", "title": "" }, { "docid": "542022", "text": "You need to set your status as self-employed the day you started online work. If that date is a little ambiguous (as is usually the case with online business), you can start with the day you first made any money. Yes, you can deduct expenses from your revenue. But you have to be sure that the expenses were purely business related. This is how it goes: You inform HMRC about the day you started work. HMRC will assign you a UTR (Unique Tax Reference) number. Depending on how much you make you might or might not need to pay Class 2 NI contributions. You'll need to tell HMRC how much you expect to earn in the current tax year. Finally, you'll need to complete a Self-Assessment at the end of the tax year. I highly recommend setting up a business banking account. Here is a link that discusses being part-time self-employed in the UK.", "title": "" }, { "docid": "418999", "text": "Not sure about the UK, but if it were in the US you need to realize the expenses can be claimed as much as the income. After having a mild heart attack when I did my business taxes the first time many years ago, a Small Business Administration adviser pointed it out. You are running the site from a computer? Deductible on an amortization schedule. Do you work from home? Electricity can be deducted. Do you drive at all? Did you pay yourself a wage? Any paperwork, fax communications, bank fees that you had to endure as work expenses? I am not an accountant, but chances are you legally lost quite a bit more than you made in a new web venture. Discuss it with an accountant for the details and more importantly the laws in your country. I could be off my rocker.", "title": "" } ]	[ { "docid": "590775", "text": "In Australia, any income you earn is taxable despite where it came from. Using your example your taxable income is $70,000. Keep in mind that with a business even as a sole trader any business expenses that contribute to the earning of your business income is deductible, reducing the final amount of tax you'll have to pay. The ATO website has lots of good information and examples to look at including tax rates. If your total income is pushing into a higher tax bracket over 30c tax per $1 earned, it may be worth looking at shifting your business to operate under a company structure that just has a fixed tax rate around 30c per $1. That said, for me, I don't want the paperwork overhead of a company yet so I'm running my side business as a sole trader too. I'd rather do that and keep it easy for now while my business gets profitable that waste time on admin structures for tax reasons even if in the shortterm it may mean slightly higher tax. In the end, you only pay tax on profit (income minus expenses) as opposed to raw/gross income. For more info there are good books in the bookshops or local library (to read free) on starting a business on the side while still working. They discuss these issues too.", "title": "" }, { "docid": "97548", "text": "In Singapore, this is sufficiently common that the Singapore IRS has a page on their website dedicated to informing employers of how to properly pay this under Responsibilites of an Employer. Specifically, tax paid by employer is taxable income for the employee (as it's really the employee's responsibility), so they must pay tax for that tax. A tax-on-tax is computed for the tax paid, which also would be owed by the employer if they were paying the full tax rate for the employee. As a clarification, this is not the employer being truly responsible for the employee's income; this is the employer compensating the employee further to offset their taxable income. This is effectively a fringe benefit, although it may be particularly useful in countries where either tax evasion is common (and thus an employer must compete with employers willing to pay under the table) or where employers are competing with others in nearby countries with lower tax rates. It is not the same thing as the employer making your income nontaxable, though, and has implications for your tax filing. Significantly, it is likely that if you have additional income beyond income from that employer, it is likely to be taxed at your highest tax rate, as the employer will likely calculate the tax due based on their income being the only income you have in that year. Edit based on emphasis in question: I'm not from Singapore nor am I a lawyer, but based on my reading of the IRAS website, it looks like you do not have to file if you have no other source of income, because they have a No-Filing Service which takes income information from your employer automatically and generates a tax bill, which presumably would be fully paid in your case. This only aplies if you have no other sources of income, however; you still have to file if you have other sources of income since your employer would not know about them. If you are eligible for this service, you should get a letter informing you as such. They also have a tool to check your filing status on their website.", "title": "" }, { "docid": "118615", "text": "Every bill you write counts as income (if the bill doesn't get paid, you would count that as an expense). In cases where you don't write bills, I think the payment you receive would count as income, but you might check that on the HMRC website. So to record your income, you can basically record the payments that you receive. Anything you pay out for your business is an expense. You keep a receipt for every expense - if you don't have a receipt, you can't count it as an expense, so keeping all the receipts is very, very important. An exception are investments, for example buying a computer that should last multiple years; there you can count a percentage of the investment as expense every year. All income, minus all expenses, is your profit. You pay tax and National Insurance contributions according to your profit. You can do whatever you like with the profit. Notice that I didn't mention any salary. Self employed means you have no salary, you have profits and do with them whatever you like. On the other hand, you pay taxes on these profits almost exactly as if they were income. If you have this blog but are also employed, you'll add the profits to your normal income statement.", "title": "" }, { "docid": "194090", "text": "You can find a lot of information at the HRMC website at http://hmrc.gov.uk. If you don't want to work as an employee, you can register as self-employed (basically a one-man band), which is quite simple, you can start your own company, which is more work but can have tax advantages, or you can find umbrella companies which will officially employ you while in reality you are a freelancer and only do your billing through them. Umbrella companies can be anywhere from totally legal to extremely dodgy. If they promise you that you pay only five percent tax on your income through ingenious tricks, that's only until the tax office finds out and they will make you pay. Between self-employed and your own company, the big difference is whether you are actually working independently or not. If you work like an employee (take someone else's orders) and claim you are a company, the tax office doesn't like that. And if you pay very little taxes, they don't like that either. So self-employed is the safer choice but you will pay more taxes, close to what a normal employee would pay. Obviously you will have to pay tax on your income and NHS insurance. Obviously you are required to tell the government (actually HMRC) about your income. Not doing so would be tax evasion and get you into deep trouble when you are caught. I don't think you have to tell them the source of your income, but not telling them might look very suspicious and might get your accounts checked carefully. And unless you design a website for the mafia, why wouldn't you tell them? The bill payer will try to deduct your bill from their profits anyway, so it's no secret. Most important to remember: When you send out a bill and receive payment, you'll have to pay tax on it. When self employed, as a rule of thumb put one third away into a savings account for your tax bill. Don't spend it all or you will find yourself in deep trouble when your taxes need paying. Plus put some more away for times when you can't find work.", "title": "" }, { "docid": "377547", "text": "\"As a minor you certainly can pay tax, the government wants its cut from you just like everyone else :-) However you do get the personal allowance like everyone else, so you won't have to pay income tax until your net income reaches £10,800 (that's the figure for the tax year from April 2015 to April 2016, it'll probably change in future years). Once you're 16, you will also have to pay national insurance, which is basically another tax, at a lower threshold. The current rates are £2.80/week if you are making £5,965 a year or more, and also 9% on any income above £8,060 (up to £42,385). Your \"\"net income\"\" or \"\"profits\"\" are the income you receive minus the expenses you have to support that income. Note that the expenses must be entirely for the \"\"business\"\", they can't be for personal things. The most important thing to do immediately is to start keeping accurate records. Keep a list of the income you receive and also the expenses you pay for hardware etc. Make sure you keep receipts (perhaps just electronic ones) for the expenses so you can prove they existed later. Keep track of that net income as the year goes on and if it starts collecting at the rate you'd have to pay tax and national insurance, then make sure you also put aside enough money to pay for those when the bill comes. There's some good general advice on the Government's website here: https://www.gov.uk/working-for-yourself/what-you-need-to-do In short, as well as keeping records, you should register with the tax office, HMRC, as a \"\"sole trader\"\". This should be something that anyone can do whatever their age, but it's worth calling them up as soon as you can to check and find out if there are any other issues. They'll probably want you to send in tax returns containing the details of your income and expenses. If you're making enough money it may be worth paying an accountant to do this for you.\"", "title": "" }, { "docid": "272820", "text": "\"In the UK, I could start my own business - either as a self-employed person, or by starting a company. With a company, the company might have £50,000 income, £5,000 cost, and pay me a £45,000 salary. In that case the company has no profit and pays no taxes, but I personally pay income tax. Or I could pay myself any salary I like, say £20,000 salary, so I pay tax on £25,000 profit and £20,000 salary. The state actually gets less money in total if I set my salary so the company makes a profit. If I'm self employed, income minus cost is my profit and I pay taxes on that. If I don't make profit, I pay no tax. Unfortunately, I also wouldn't have any money to buy food, pay the rent, and so on and so on. I'd have the same income and pay the same taxes as someone who is unemployed. There are \"\"businesses\"\" that are just run for the enjoyment of the owner and don't make profit. Rich guy buys a farm and starts breeding race horses, that kind of thing. In that case, there is zero difference between a guy breeding race horses and calling it a \"\"business\"\" and another guy breeding race horses and calling it a hobby. Neither makes money and neither pays taxes.\"", "title": "" }, { "docid": "417769", "text": "How do I directly get my Freelancing amount in my Axis bank account? Do I need to inform my Bank before receiving any such payment? Yes you can get it directly into your Axis Bank Account. You would need to inform your client your Bank Account Number, Bank Name and Address and Swift BIC or IFSC Code [Axis Bank website or Branch can tell you]. You can receive credits in Euro's. Upon receipt Axis Bank will automatically convert this into Rupees using standard rate. Your Bank [Axis] may also charge some Bank fees for the wire transfer. How do I pay tax for this extra income in India? You would need to treat this as income and add it to total income including salary and calculate tax accordingly. You can pay taxes online using Income Tax India website. You can also approach a CA who would do the tax computation, paying taxes and filing returns for as little as Rs 1000 - 2000/- Edit: IBAN is International Bank Account Number. Explain to you client that India does not subscribe to IBAN. Its right now only used by Europe and Australia. Give you normal Bank Account Number. Please call up your Bank / walk into your Branch to get the SWIFT BIC. It will be something like this http://www.theswiftcodes.com/india/page/3/", "title": "" }, { "docid": "3181", "text": "> Operating in a country that allows you to make profit, in my opinion, establishes a duty to pay one's fair share of taxes. Paying legislators to make laws enabling tax avoidance is, in my mind, unethical. Clearly we have a different idea of what is ethical and not. You have stumbled upon the heart of exactly why Burger King's actions (and those of other companies that do similar things) are perfectly justified, although perhaps not in the manner you intended. In the entire developed world, corporations are taxed at a certain rate on the income that they make as a result of business operations in that country. In the US, US headquartered corporations are taxed at a certain rate not only on the income that they make a result of business operations in that country, but also on the income that they make as the result of business operations in other countries. Operating in a country that allows you to make a profit established a duty to pay one's fair share of taxes. Operating in a country that allows you to make a profit does not establish any duty to pay one's fair share of taxes to an entirely different country*. Or at least, no moral or ethical obligation to do so. The US may try to make a legal obligation to do so, but I certainly can't fault any company which tries to avoid that obligation, since the obligation is inherently unjust in the first place. If you don't want companies doing stuff like this, might I suggest that your country should stop imposing such ridiculous tax laws, and get in line with the rest of the developed world. Every other country in the world is content to tax their fair slice of the pie for stuff that happens in their borders; only the US expects a bite out of everyone else's pie too. Same should go for personal income earned by US citizens living abroad. They should have no obligation to pay US income taxes.", "title": "" }, { "docid": "211485", "text": "\"Being self-employed, your \"\"profit\"\" is calculated as all the bills you send out, minus all business-related cost that you have (you will need a receipt for everything, and there are different rules for things that last for long time, long tools, machinery). You can file your taxes yourself - the HRS website will tell you how to, and you can do it online. It's close to the same as your normal online tax return. Only thing is that you must keep receipts for all the cost that you claim. Your tax: Assuming your gross salary is £25,000 and your profits are about £10,000, you will be paying 8% for national insurance, and 20% income tax. If you go above £43,000 or thereabouts, you pay 40% income tax on any income above that threshold, instead of 20%, but your national insurance payments stop.\"", "title": "" }, { "docid": "396066", "text": "Yes, if you can split your income up over multiple years it will be to your advantage over earning it all in one year. The reasons are as you mentioned, you get to apply multiple deductions/credits/exemptions to the same income. Rather than just 1 standard deduction, you get to deduct 2 standard deductions, you can double the max saved in an IRA, you benefit more from any non-refundable credits etc. This is partly due to the fact that when you are filing your taxes in Year 1, you can't include anything from Year 2 since it hasn't happened yet. It doesn't make sense for the Government to take into account actions that may or may not happen when calculating your tax bill. There are factors where other year profit/loss can affect your tax liability, however as far as I know these are limited to businesses. Look into Loss Carry Forwarded/Back if you want to know more. Regarding the '30% simple rate', I think you are confusing something that is simple to say with something that is simple to implement. Are we going to go change the rules on people who expected their mortgage deduction to continue? There are few ways I can think of that are more sure to cause home prices to plummet than to eliminate the Mortgage Interest Deduction. What about removing Student Loan Interest? Under a 30% 'simple' rate, what tools would the government use to encourage trade in specific areas? Will state income tax deduction also be removed? This is going to punish those in a state with a high income tax more than those in states without income tax. Those are all just 'common' deductions that affect a lot of people, you could easily say 'no' to all of them and just piss off a bunch of people, but what about selling stock though? I paid $100 for the stock and I sold it for $120, do I need to pay $36 tax on that because it is a 'simple' 30% tax rate or are we allowing the cost of goods sold deduction (it's called something else I believe when talking about stocks but it's the same idea?) What about if I travel for work to tutor individuals, can I deduct my mileage expenses? Do I need to pay 30% income tax on my earnings and principal from a Roth IRA? A lot of people have contributed to a Roth with the understanding that withdrawals will be tax free, changing those rules are punishing people for using vehicles intentionally created by the government. Are we going to go around and dismantle all non-profits that subsist entirely on tax-deductible donations? Do I need to pay taxes on the employer's cost of my health insurance? What about 401k's and IRA's? Being true to a 'simple' 30% tax will eliminate all 'benefits' from every job as you would need to pay taxes on the value of the benefits. I should mention that this isn't exactly too crazy, there was a relatively recent IRS publication about businesses needing to withhold taxes from their employees for the cost of company supplied food but I don't know if it was ultimately accepted. At the end of the day, the concept of simplifying the tax law isn't without merit, but realize that the complexities of tax law are there due to the complexities of life. The vast majority of tax laws were written for a reason other than to benefit special interests, and for that reason they cannot easily be ignored.", "title": "" }, { "docid": "457968", "text": "Under what section do I declare my profits when I pay tax? You have to declare this as income from other source and pay tax as per tax brackets. I'm from India and have been trading in binary options for a while now Trading in India on binary options is illegal. If you are using Forex from India for trading, this is not allowed as per Foreign Exchange Management Act.", "title": "" }, { "docid": "196374", "text": "\"First to clear a few things up. It is definitely not a gift. The people are sending you money only because you are providing them with a service. And for tax purposes, it is not a \"\"Donation\"\". It has nothing to do with the fact that you are soliciting the donation, as charitable organizations solicit donations all the time. For tax purposes, it is not a \"\"Donation\"\" because you do not have 501(c)(3) non profit status. It is income. The question is then, is it \"\"Business\"\" income, or \"\"Hobby\"\" related income? Firstly, you haven't mentioned, but it's important to consider, how much money are you receiving from this monthly, or how much money do you expect to receive from this annually? If it's a minimal amount, say $50 a month or less, then you probably just want to treat it as a hobby. Mostly because with this level of income, it's not likely to be profitable. In that case, report the income and pay the tax. The tax you will owe will be minimal and will probably be less than the costs involved with setting up and running it as a business anyway. As a Hobby, you won't be able to deduct your expenses (server costs, etc...) unless you itemize your taxes on Schedule A. On the other hand if your income from this will be significantly more than $600/yr, now or in the near future, then you should consider running it as a business. Get it clear in your mind that it's a business, and that you intend it to be profitable. Perhaps it won't be profitable now, or even for a while. What's important at this point is that you intend it to be profitable. The IRS will consider, if it looks like a business, and it acts like a business, then it's probably a business... so make it so. Come up with a name for your business. Register the business with your state and/or county as necessary in your location. Get a bank account for your business. Get a separate Business PayPal account. Keep personal and business expenses (and income) separate. As a business, when you file your taxes, you will be able to file a Schedule C form even if you do not itemize your taxes on Schedule A. On Schedule C, you list and total your (business) income, and your (business) expenses, then you subtract the expenses from the income to calculate your profit (or loss). If your business income is more than your business expenses, you pay tax on the difference (the profit). If your business expenses are more than your business income, then you have a business loss. You would not have to pay any income tax on the business income, and you may be able to be carry the loss over to the next and following years. You may want to have a service do your taxes for you, but at this level, it is certainly something you could do yourself with some minimal consultations with an accountant.\"", "title": "" }, { "docid": "115264", "text": "I think that author does a disservice by writing such seemingly sensible articles without actually knowing how things work. If I didn’t know better, I would think this guy was teaching me something. It’s a shame he did not do research before he started writing. Let’s say you buy a classic car. You take super good care of it, all original, mint condition. You paid cash for it out of your savings. This is a balance sheet transaction that has nothing to do with income. You traded your cash asset for a classic car asset. Now let’s say this car is so rare and you keep it in such good condition that it gains value every year. Maybe it was worth $15k when you bought it, but this year it’s already worth $17k. Great job on making a great purchase! But is that $2k gain counted as income to you? No, it is not. The value of that asset on your balance sheet went up, but you did not make anything off of that increase in value because you have not sold it. If you had to pay taxes on the increase in value every year, those taxes would essentially force you to sell that car to pay the taxes just because you took care of it. Additionally, in the long term, no one would want to own anything, so this would destroy the value of everyone’s stuff, but I digress. In this example, amazon stock is the car. The author is seeing the increase in stock value adding to the balance sheets of the investors who bought the stock and confusing that with income. Back to our example, let’s say your car increased in value $2k a year for two years and you decide to sell it for $19k - now we are about to realize some income! Since you bought it for $15k and sold for $19k, you earned an income of the difference, or $4k. Your income wasn’t $19k, because you originally put $15k in cash into the car. That cash was already saved from income you made in the past, and it is not counted again as income in this sale. Because you did not work for this new car sale income, but it was derived from asset growth, the income is called capital gains. You invested your capital ($15k) into the asset (car), and that asset appreciated. When you sold it, you received capital (money) back in exchange for that asset. The capital you received is more than what you invested, which is to say you gained $4k of capital by investing in and then selling your asset (car). Because you held the car for two years, you qualify for lower long term capital gains tax rate on that $4k. Had you sold it after year 1, you would’ve paid your regular normal income tax rate on those capital gains. Either way, you owe the tax when you sell the asset, not when it appreciates. I’m sure you realize this already, but if we change the car to amazon stock in my story, this is exactly how it works with investors. The author gets several things wrong 1 - amazon profits are not passed through to shareholders for income tax purposes. If amazon paid dividends, those dividends would be taxed at payout at the long term capital gains rate, and they would be paid out of cash amazon has left after it already paid corporate taxes on profits. Amazon has decided they can add more value to investors by using cash to grow instead of paying dividends. When the investors sell the stock, they will owe capital gains on the growth of that stock. If amazon is correct that using cash to grow, then investors will effectively pay more when they sell the stock than they would pay today if dividends were paid. 2 - asset appreciation is not income. Those investors will realize the income when they sell the stock, and they will pay the tax then. 3 - he is missing the point entirely on why amazon runs a low profit or how business strategy translates into financials. Low prices are not a function of low profitability. Low profitability could be an adverse result of low pricing, but being low profit in order to be low price is a ridiculous and failing strategy. Amazon’s low pricing is a function of their unparalleled buying power, unparalleled consumer and product data, amazing logistics prowess, clever loyalty programs like amazon prime, and many other brilliant things they’ve done. Their low profitability is a function of their investment in things like amazon fresh, amazon Alexa, drone delivery, automated convenience stores, building out cloud computing infrastructure, and many other R&D projects, $4 billion in original content spending for amazon prime video, and all kinds of expenditures years ahead of when they become profitable. By the time consumers want it, amazon already built it three years ago - this is the power of amazon. Sometimes multi billion dollar experiments fail, and all that money was for nothing. Sometimes they lose money for a few years and then become the infrastructure that runs a third of the internet. Amazon does not let fear of failure stop them, they invest in growth with their cash. This is how Bezos thinks - how do we build the future, not how can I avoid tax I do need to make a disclaimer here - there could be special tax treatment of classic cars that makes my example not work. Also classic cars may not appreciate in value. I don’t know anything about classic cars, I just picked a politically neutral thing to put in my story and made some assumptions to illustrate how capital gains work. My story is definitely how stocks work, and probably cars, but I just want to point out that I don’t know shit about car collecting.", "title": "" }, { "docid": "512267", "text": "It is best to take advise from / appoint a professional CA. Will I have to pay GST? No GST is applicable. Exports outside of India do not have GST. Do I have to collect TDS when I send money to the PUBLISHERS ? No But another guy said, I have to pay 18% tax when receiving and sending payments, apart from that I have to collect 30.9% TDS when sending payment to the PUBLISHERS(outside India). There is only income tax applicable on profits. So whatever you get from Advertisers less of payments to publishers less of your expenses is your profit. Since you are doing this as individual, you will have to declare this as income from other sources and pay income tax as appropriate. Note there are restrictions on sending payments outside of India plus there are exchange rate fluctuations. It is best you open an Foreign Currency Resident [or Domestic] Account. This will enable you payout someone without much issues. Else you will have to follow FEMA and LRS schemes of RBI.", "title": "" }, { "docid": "183612", "text": "Assuming you buy the services and products beforehand and then provide them to your clients. Should the cost of these products and services be deducted from my declared income or do I include them and then claim them as allowable expenses? You arrive at your final income after accounting for your incomings and outgoings ? regularly buys products and services on behalf of clients These are your expenses. invoice them for these costs after These are your earnings. These are not exactly allowable expenses, but more as the cost of doing your business, so it will be deducted from your earnings. There will be other business expenses which you need to deduct from your earnings and then you arrive at your income/profit. So before you arrive at your income all allowable expenses have been deducted. include on my invoices to clients VAT if you charge VAT. Any charges you require them to pay i.e. credit card charges etc. You don't need to inform clients about any costs you incur for doing your business unless required by law. If you are unsure about something browse the gov.uk website or obtain the services of an accountant. Accounting issues might be costly on your pocket if mistakes are committed.", "title": "" }, { "docid": "314342", "text": "\"Many individual states, counties, and cities have their own income taxes, payroll taxes, sales taxes, property taxes, etc., you will need to consult your state and local government websites for information about additional taxes that apply based on your locale. Wages, Salaries, Tips, Cash bonuses and other taxable employee pay, Strike benefits, Long-term disability, Earnings from self employment Earned income is subject to payroll taxes such as: Earned income is also subject to income taxes which are progressively higher depending on the amount earned minus tax credits, exemptions, and/or deductions depending on how you file. There are 7 tax rates that get progressively larger as your income rises but only applies to the income in each bracket. 10% for the first 18,650 (2017) through 39.6% for any income above 470,700. The full list of rates is in the above linked article about payroll taxes. Earned income is required for contributions to an IRA. You cannot contribute more to an IRA than you have earned in a given year. Interest, Ordinary Dividends, Short-term Capital Gains, Retirement income (pensions, distributions from tax deferred accounts, social security), Unemployment benefits, Worker's Compensation, Alimony/Child support, Income earned while in prison, Non-taxable military pay, most rental income, and S-Corp passthrough income Ordinary income is taxed the same as earned income with the exception that social security taxes do not apply. This is the \"\"pure taxable income\"\" referred to in the other linked question. Dividends paid by US Corporations and qualified foreign corporations to stock-holders (that are held for a certain period of time before the dividend is paid) are taxed at the Long-term Capital Gains rate explained below. Ordinary dividends like the interest earned in your bank account are included with ordinary income. Stocks, Bonds, Real estate, Carried interest -- Held for more than a year Income from assets that increase in value while being held for over a year. Long term capital gains justified by the idea that they encourage people to hold stock and make long term investments rather than buying and then quickly reselling for a short-term profit. The lower tax rates also reflect the fact that many of these assets are already taxed as they are appreciating in value. Real-estate is usually taxed through local property taxes. Equity in US corporations realized by rising stock prices and dividends that are returned to stock holders reflect earnings from a corporation that are already taxed at the 35% Corporate tax rate. Taxing Capital gains as ordinary income would be a second tax on those same profits. Another problem with Long-term capital gains tax is that a big portion of the gains for assets held for multiple decades are not real gains. Inflation increases the price of assets held for longer periods, but you are still taxed on the full gain even if it would be a loss when inflation is calculated. Capital gains are also taxed differently depending on your income level. If you are in the 10% or 15% brackets then Long-term capital gains are assessed at 0%. If you are in the 25%, 28%, 33%, or 35% brackets, they are assessed at 15%. Only those in the 39.6% bracket pay 20%. Capital assets sold at a profit held for less than a year Income from buying and selling any assets such as real-estate, stock, bonds, etc., that you hold for less than a year before selling. After adding up all gains and losses during the year, the net gain is taxed as ordinary income. Collectibles held for more than a year are not considered capital assets and are still taxed at ordinary income rates.\"", "title": "" }, { "docid": "537916", "text": "\"Do I have to pay the stock investment income tax if I bought some stocks in 2016, it made some profits but I didn't sell them at the end of 2016? You pay capital gains taxes only when you sell the stocks. When you sell the stock within a year you will pay the short term capital gains rate which is the same rate as your ordinary income. If the stock pays dividends, however, you will have to pay taxes in the year that the dividend was paid out to you. I bought some stocks in 2011, sold them in 2012 and made some gains. Which year of do I pay the tax for the gains I made? You would pay in 2012, likely at the short term gain rate. I bought some stocks, sold them and made some gains, then use the money plus the gains to buy some other stocks before the end of the same year. Do I have to pay the tax for the gains I made in that year? Yes. There is a specific exception called the \"\"Wash Sale Rule\"\", but that would only apply if you lost money on the original sale and bought a substantially similar or same stock within 30 days. Do I get taxed more for the money I made from buying and selling stocks, even if the gains is only in hundreds? More than what? You pay taxes based on the profit you make from the investment. If you held it less than a year it is the same tax rate as your regular income. If you held it longer you pay a lower tax rate which is usually lower than your regular tax rate.\"", "title": "" }, { "docid": "9753", "text": "The Australian Tax Office website shows Tax Rates for individuals based on the income earned in the Financial Year. Calculating what you'll be taxed For instance, it show that every dollar you earn up to $18,200, you are not taxed. Every dollar over that, up to $37k is taxed at 19 cents. And so on.. Example 1 So as an example, if your income for the year is $25,000 you will be taxed $1292. Working: Here's how it's look if you were doing it in a spreadsheet using the Tax Rates table on the ATO website as a guide: Example 2 If you income is $50,000, it'd look like this: Withholding Your employer is obligated to remove the taxable part from your wage each time your paid. They do that using the calculation above. If at the end of the financial year, the ATO determines that too much as been withheld (ie. you've claimed deductions that've reduce your taxable income to less than what your actual income is), that's when you may be eligible for a refund. If your employer didn't withhold enough or you had income from other sources that haven't been taxed already, then you may actually need to pay rather than expecting a refund. Your question If you earn $18,200 in the year and for some reason your employer did withhold tax from your pay, say $2,000, then yes, you'll get all that $2,000 back as a refund since the Tax Rate for income up to $18,200 is $0.00. If you earned $18,201 and your employer withheld $2000, you'd get $1999.81 back as a refund ($2000 - 19c). You have to pay 19c tax on that $1 over $18,200.", "title": "" }, { "docid": "132780", "text": "First - get a professional tax consultation with a NY-licensed CPA or EA. At what point do I need to worry about collecting sales taxes for the city and state of New York? Generally, from the beginning. See here for more information on NYS sales tax. At what point do I need to worry about record-keeping to report the income on my own taxes? From the beginning. Even before that, since you need the records to calculate the costs of production and expenses. I suggest starting recording everything, as soon as possible. What sort of business structures should I research if I want to formalize this as less of a hobby and more of a business? You don't have to have a business structure, you can do it as a sole proprietor. If you're doing it for-profit - I suggest treating it as a business, and reporting it on your taxes as a business (Schedule C), so that you could deduct the initial losses. But the tax authorities don't like business that keep losing money, so if you're not expecting any profit in the next 3-4 years - keep it reported as a hobby (Misc income). Talk to a licensed tax professional about the differences in tax treatment and reporting. You will still be taxed on your income, and will still be liable for sales tax, whether you treat it as a hobby or as a business. Official business (for-profit activity) will require additional licenses and fees, hobby (not-for-profit activity) might not. Check with the local authorities (city/county/State).", "title": "" }, { "docid": "397920", "text": "I heard that a C-Corp being a one person shop (no other employees but the owner) can pay for the full amount 100% of personal rent if the residence is being used as a home office. Sure. Especially if you don't mind being audited. Technically, it doesn't matter how the money gets where it goes as long as the income tax filings accurately describe the tax situation. But the IRS hates it when you make personal expenses from a business account, even if you've paid the required personal income tax (because their computers simply aren't smart enough to keep up with that level of chaos). Also, on a non-tax level, commingling of business and personal funds can reduce the effectiveness of your company's liability protection and you could more easily become personally liable if the company goes bankrupt. From what I understand the 30% would be the expense, and the 70% profit distribution. I recommend you just pay yourself and pay the rent from your personal account and claim the allowed deductions properly like everyone else. Why & when it would make sense to do this? Are there any tax benefits? Never, because, no. You would still have to pay personal income tax on your 70% share of the rent (the 30% you may be able to get deductions for but the rules are quite complicated and you should never just estimate). The only way to get money out of a corporation without paying personal income tax is by having a qualified dividend. That's quite complicated - your accounting has to be clear that the money being issued as a qualified dividend came from an economic profit, not from a paper profit resulting from the fact that you worked hard without paying yourself market value.", "title": "" }, { "docid": "57263", "text": "\"US federal tax law distinguishes many types of income. For most people, most of their income is \"\"earned income\"\", money you were paid to do a job. Another category of income is \"\"capital gains\"\", money you made from the sale of an asset. For a variety of reasons, capital gains tax rates are lower than earned income tax rates. (For example, it is common that much of the gain is not real profit but inflation. If you buy an asset for $10,000 and sell it for $15,000, you pay capital gains tax on the $5,000 profit. But what if prices in general since you bought the asset have gone up 50%? Then your entire profit is really inflation, you didn't actually make any money -- but you still have to pay a tax on the paper gain.) So if you make your money by investing in assets -- buying and selling at a profit -- you will pay lower taxes than if you made the same amount of money by receiving a salary from a job, or by running a business where you sell your time and expertise rather than an asset. But money made from assets -- capital gains -- is not tax free. It's just a lower tax. It MIGHT be that when combined with other deductions and tax credits this would result in you paying no taxes in a particular year. Maybe you could avoid paying taxes forever if you can take advantage of tax loopholes. But for most people, making money from capital gains could result in lower taxes per dollar of income than someone doing more ordinary work. Or it could result in higher taxes, if you factor in inflation, net present value of money, and so on. BTW Warren Buffet's \"\"secretary\"\" is not a typist. She apparently makes at least $200,000 a year. http://www.forbes.com/sites/paulroderickgregory/2012/01/25/warren-buffetts-secretary-likely-makes-between-200000-and-500000year/#ab91f3718b8a. And side note: if Warren Buffet thinks he isn't paying enough in taxes, why doesn't he voluntarily pay more? The government has a web site where citizens can voluntarily pay additional taxes. In 2015 they received $3.9 million in such contributions. http://www.treasurydirect.gov/govt/reports/pd/gift/gift.htm\"", "title": "" }, { "docid": "53814", "text": "lets sat If I buy a house on company's name, It will declared as expense and will deduct from profit. but I am not sure If I can rent it out as a IT LTD company. that's my questions. Buying a house is not an expense, it is a transfer of assets. The house itself, is an asset. So if you have $100,000 in cash, buy a house for $35,000, your total assets will remain the same ($100,000), but your asset mix will be different (instead of $100,000 in cash, you now have $65,000 in cash, and $35,000 in property). You can expense the costs associated with buying the house (e.g. taxes, interest, legal fees), but the house itself stays on the asset side of your balance sheet. To refine the example above, if you buy the house for $35,000, and pay $5,000 in misc fees related to purchasing the house, your assets are now $95,000 ($60,000 in cash, $35,000 in house): the $5,000 reduction is from the actual fees associated with the purchase. It is these fees that lower your profit. Being not familiar with UK rules, in Canada and the US, and likely the UK, you would then depreciate the house over its useful life. The depreciation expense is deducted from your annual net income. If you rent out the house, what you can do is expense any maintenance fees, taxes, etc., on the house itself. This expense will count as a negative towards the rental income, lowering your effective taxable income from the rental. E.g. rent out a flat at $1,000/month, but your property taxes are $3,500/year, so your net income for tax purposes (i.e. your taxable income in this case) is $12,000-$3,500=$8,500.", "title": "" }, { "docid": "252843", "text": "FICA taxes are separate from federal and state income taxes. As a sole proprietor you owe all of those. Additionally, there is a difference with FICA when you are employed vs. self employed. Typically FICA taxes are actually split between the employer and the employee, so you pay half, they pay half. But when you're self employed, you pay both halves. This is what is commonly referred to as the self employment tax. If you are both employed and self employed as I am, your employer pays their portion of FICA on the income you earn there, and you pay both halves on the income you earn in your business. Edit: As @JoeTaxpayer added in his comment, you can specify an extra amount to be withheld from your pay when you fill out your W-4 form. This is separate from the calculation of how much to withhold based on dependents and such; see line 6 on the linked form. This could allow you to avoid making quarterly estimated payments for your self-employment income. I think this is much easier when your side income is predictable. Personally, I find it easier to come up with a percentage I must keep aside from my side income (for me this is about 35%), and then I immediately set that aside when I get paid. I make my quarterly estimated payments out of that money set aside. My side income can vary quite a bit though; if I could predict it better I would probably do the extra withholding. Yes, you need to pay taxes for FICA and federal income tax. I can't say exactly how much you should withhold though. If you have predictable deductions and such, it could be lower than you expect. I'm not a tax professional, and when it comes doing business taxes I go to someone who is. You don't have to do that, but I'm not comfortable offering any detailed advice on how you should proceed there. I mentioned what I do personally as an illustration of how I handle withholding, but I can't say that that's what someone else should do.", "title": "" }, { "docid": "412855", "text": "\"Q) Will I have to submit the accounts for the Swiss Business even though Im not on the payroll - and the business makes hardly any profit each year. I can of course get our accounts each year - BUT - they will be in Swiss German! You will have to submit on your income from the business. The term \"\"partnership\"\" refers to a specific business entity type in the U.S. I'm not sure if you're using it the same way. In a partnership in the U.S. you pay income tax on your share of the partnership's income whether or not you actually receive income in your personal account. There's not enough information here to know if that applies in your case. (In the U.S., the partnership itself does not pay income tax - It is a \"\"disregarded entity\"\" for tax purposes, with the tax liability passed through to the partners as individuals.) Q) Will I need to have this translated!? Is there any format/procedure to this!? Will it have to be translated by my Swiss accountants? - and if so - which parts of the documentation need to be translated!? As regards language, you will file a tax return on a U.S. form presumably in English. You will not have to submit your account information on any other form, so the fact that your documentation is in German does not matter. The only exception that comes to mind is that you could potentially get audited (just like anyone else filing taxes in the U.S.) in which case you might need to produce your documentation. That situation is rare enough that I wouldn't worry about it though. I'm not sure if they'd take it in German or force you to get a translation. I was told that if I sell the business (and property) after I aquire a greencard - that I will be liable to 15% tax of the profit I'd made. I also understand that any tax paid (on selling) in Switzerland will be deducted from the 15%!? Q) Is this correct!? The long-term capital gains rate is 15% for most people. (At very high incomes it is 20%.) It sounds like you would qualify for long-term (held for greater than 1 year) capital gains in this case, although the details might matter. There is a foreign tax credit, but I'm not completely sure if it would apply in this case. (If forced to guess, I would say that it does.) If you search for \"\"foreign tax credit\"\" and \"\"IRS\"\" you should get to the information that you need pretty quickly. I will effectively have ALL the paperwork for this - as we'll need to do the same in Switzerland. But again, it will be in Swiss German. Q) Would this be a problem if its presented in Swiss German!? Even in this case you will not need to submit any of your paperwork to the IRS, unless you get audited. See earlier comments.\"", "title": "" }, { "docid": "559884", "text": "The dividend quoted on a site like the one you linked to on Yahoo shows what 1 investor owning 1 share received from the company. It is not adjusted at all for taxes. (Actually some dividend quotes are adjusted but not for taxes... see below.) It is not adjusted because most dividends are taxed as ordinary income. This means different rates for different people, and so for simplicity's sake the quotes just show what an investor would be paid. You're responsible for calculating and paying your own taxes. From the IRS website: Ordinary Dividends Ordinary (taxable) dividends are the most common type of distribution from a corporation or a mutual fund. They are paid out of earnings and profits and are ordinary income to you. This means they are not capital gains. You can assume that any dividend you receive on common or preferred stock is an ordinary dividend unless the paying corporation or mutual fund tells you otherwise. Ordinary dividends will be shown in box 1a of the Form 1099-DIV you receive. Now my disclaimer... what you see on a normal stock quote for dividend in Yahoo or Google Finance is adjusted. (Like here for GE.) Many corporations actually pay out quarterly dividends. So the number shown for a dividend will be the most recent quarterly dividend [times] 4 quarters. To find out what you would receive as an actual payment, you would need to divide GE's current $0.76 dividend by 4 quarters... $0.19. So you would receive that amount for each share of stock you owned in GE.", "title": "" }, { "docid": "564453", "text": "It will depend on how much you expect to earn this way, and whether you expect the company to become profitable soon. Has the company just not made a profit yet, or has it actually made a significant loss that your invoices would just be offsetting? If you're earning over £10,000 per year then invoicing through the company is preferable. Above that level, you'd be taking money from the company as dividends after paying 20% corporation tax with no other tax to pay on your personal tax return. As a sole trader you'd be paying 20% income tax and 9% NI. (Note however that the company can only pay dividends from profits, which is a problem if there are significant losses to offset.) Below £10,000, there's little difference. Through the company, you can take a salary of £7956 per year without paying any income tax or NI. With the new £2000 discount on employers' NI you could then take salary up to £10,000 and just pay 12% employee's NI. As a sole trader, you pay 9% Class 4 NI over £7956 and a fixed £143 per year for Class 2 NI. Paying 9% rather than 12% saves you £60, but then you add the £143. In practice the company would work out more expensive at this level because you'll probably want to pay an accountant to deal with the payroll for you. Having the company repay your £2000 from the invoices doesn't really save any tax if the company will become profitable in the future. You don't pay any tax now since the money you receive isn't income, and the company doesn't pay any tax if the extra £2000 of revenue doesn't put it back in profit. However, if the company is profitable next year then it will have an extra £2000 of profit that would otherwise have been offset against this year's loss, and you do end up paying 20% corporation tax on the £2000. You could still have the company repay the loan in order to delay the tax liability, but it's not really tax free money. Loaning additional money to the company has no tax benefit, you just give the company £1000 and get your original £1000 back later. You pay no tax and neither does the company, but it was your money in the first place.", "title": "" }, { "docid": "271568", "text": "\"From your explanation the Sole Trader option is more appropriate and certainly easier to manage. There are many differences but the pertinent and most important ones are as follows. The main difference in your case would be tax and administration. As a sole trader you would need to do a tax return once a year and if you earned less than £11.5k you wouldn't have to pay any UK tax, assuming you have no other income and are a \"\"standard\"\" tax payer. The current tax allowance is £11.5k although this can change. Submitting your own tax return is relatively straighforward although you may want to consult an accountant. It is generally easier to run as sole trader versus a Limited Company, ie less paperwork and beaureaucracy. If you go down the Limited Company route, the company would be liable to pay Corporation Tax on any profits and this process is more complicated and you would probably need an accountant to do that for you, which is likely to cost a few hundred pounds every year. You can do it yourself but the process is not as simple as doing your own income tax return. Also as a sole trader you can do what you like with any income, you can spend it and treat it as your own wages. You can't do that if you set up a Limited Company as the income is \"\"owned\"\" by the company and so you would need to in effect pay yourself a wage from the company. In other words it's more complex than if you are a sole trader. The main advantage to a Limited Company is that it is easier to sell the business if you want to at a later date. There is nothing stopping you setting up a Limited Company later on, after beign a sole trader if you want to. They can also be more tax-efficient but this would not be relevant to your case if you are earning relatively small sums, if your income increases then you may want to reconsider. You can see more information here: https://www.duport.co.uk/company-formation/sole-trader-vs-limited-company.php (I have been both a sole trader and also set up my own Limited Company)\"", "title": "" }, { "docid": "474042", "text": "The benefit of paying into a pension is that the payment is effectively made from pre-tax money. Either you pay from your own pocket and then you get income tax relief on the payment, i.e. your gross salary is reduced by the gross pension contribution and income tax is recalculated with the excess either refunded to you or put in your pension (the details are a bit more complicated depending on your marginal tax rate, but the end result is the same). Or your company pays, and then you are never charged tax on the payment in the first place. From the company's point of view, the two are roughly the same. Either it pays you who then pays into your pension, or it pays straight into your pension. Either way the money going out from the company is treated as a cost that is offset against the company's revenue, reducing the amount of corporation tax the company has to pay. There are some National Insurance advantages to paying directly into the pension; neither you nor the company gets relief on NI if the payment goes via you, but no NI is paid in the first place if it goes direct from the company. [EDIT: your question is actually worded to suggest that you want to lend your company money from your own pocket, and then have that loan directly discharged by the company paying into your pension. That's no different to you just paying into your pension directly, and wouldn't have any better tax implications. For the rest of my answer, I assume that the idea is actually to lend your company money that it uses to make an immediate contribution to your pension (as part of your pay from that company), and then the company will repay the loan later by returning the money to you personally. Your pension and you are two separate entities legally.] However, in your case, what you're proposing is that the company should effectively make a loss paying into your pension: it's going to end up with more costs than revenue. So, there won't be any immediate tax saving because there wasn't revenue to pay corporation tax on in the first place. You also won't save tax because the loan will be made from previously taxed income or whatever. However, there will be a tax loss that can be carried forward and offset against future profits, so if you expect the company to make money in future to repay the loan, you might end up saving some corporation tax. You can also sometimes carry a tax loss back one year, so if your company had profits last year you could get some corporation tax back immediately. The repayment of the loan itself won't be subject to income tax as it's not income. So unless you can carry the loss back, you won't get any immediate tax relief by doing this, but it might give you a way to carry forward your annual allowance to future years, i.e. use it now and get the tax advantage later. However, the annual allowance can already be carried forward by up to three years, so this is only worthwhile if you expect that future revenue to repay the loan to arrive more than three years later. Also, this is only worthwhile if you'll continue to max out the annual allowance for paying into your pension in future years, otherwise you might as well just make the pension payment using that same revenue in future years. However, even if this beneficial tax-wise, I'm not sure if it's actually allowed; this might be viewed as an artificial transaction to avoid tax, and that could lead to HMRC disallowing the future tax relief. You might need to ask HMRC or an accountant about that. If you do make the loan, make sure it's clearly documented so you can show in future why the repayment shouldn't be treated as income.", "title": "" }, { "docid": "291614", "text": "how much taxes would I pay on my income from the rent they would pay me? The same as on any other income. California doesn't have any special taxes for rental/passive income. Bothe CA and the Federal tax laws do have special treatment, but it is for losses from rental. Income is considered unearned regular income and is taxed at regular brackets. Would I be able to deduct the cost of the mortgage from the rental income? The cost of mortgage, yes. I.e.: the interest you pay. Similarly you can deduct any other expense needed to maintain the property. This is assuming you're renting it out at FMV. If not, would I pay the ordinary income tax on that income? In particular, would I pay CA income tax on it, even though the property would be in WA? Yes. Don't know how WA taxes rental income, but since you are a California tax resident - you will definitely be taxed by California on this, as part of your worldwide income.", "title": "" }, { "docid": "205341", "text": "\"Am I on crack, or do the perceived tax savings via S-Corp distributions really not matter at a certain level of business income? You're not on crack. Generally, if all the income is generated by your own personal services - this is the outcome. The benefit of S-Corp is when you have employees who generate your income, and you distribute to yourself profits that come out of other's personal services. In this case your distributions are exempt from FICA since it is not in fact a self-employment income. You'd still have to pay yourself a reasonable salary for your position (as a manager/officer), but it wouldn't have to cover all of the available profits. So if the IRS takes a position against you it would be that your salary should be to include the whole profits, since it is the compensation to you for the personal services that produced the income to the corporation (you). In many cases they might agree that a salary at the SS maximum limit would be reasonable - but that's only a speculation of mine. In that case you might gain some portion of the medicare tax (with the recent law changes at the levels you're talking about you'll pay some medicare anyway). There are a lot of accountants who take more aggressive position saying that not all of the distributions are liable for SE taxes, even if you're the sole employee of the corporation. These cases often end up in the Tax Court, and whatever the outcome, your legal fees become higher than the FICA savings. What is probably missing in your picture is the SS limit of (currently $112K) above which you don't pay social security tax, so whether you get it as a salary or as a distribution - that limit is the same. That is why you don't see a significant difference. I know there are a lot of accountants who'd disagree, but I would argue that for a sole employee of your company, S-Corp doesn't provide significant benefits over the disregarded LLC taxation, but has some additional overhead that adds to your expenses. Here's a link to a lawyer's blog where he suggests (and says many accountants follow) 60/40 division between salary and distributions. I.e.: his take, similarly to mine, is that most of the earnings have to be treated as salary. In your case, when the total is about 300K - you indeed will not get any FICA savings with such a division other than some of the medicare. Unusually low wages when compared to distributions can draw unwanted IRS scrutiny and an audit. An unfavorable audit will likely result in some portion of the distributions being reclassified as earned income for federal income tax purposes, which results in a deficiency assessment (i.e., a tax bill), interest on those unpaid taxes, and IRS penalties. The article also talks about the Watson case (one of the Tax Court cases I referred to), which can be used as the guidelines for determining the \"\"reasonable\"\" compensation. Talk to your tax adviser. I'm neither a tax adviser nor a tax professional. For a tax advice contact a CPA/EA licensed in your state. This is not a tax advice, just my personal opinion.\"", "title": "" } ]
5abd7bd355429924427fcffe	Compiere is distributed by which software company?	[ { "docid": "228424", "text": "Compiere (pronounced KOM-pyeh-reh, \"to accomplish, complete, fulfill\" in Italian) is an open source ERP and CRM business solution for the Small and Medium-sized Enterprise (SME) in distribution, retail, service and manufacturing. Compiere is distributed by Consona Corporation and through a Partner Network, a collection of trained and authorized business partners.", "title": "" }, { "docid": "29380094", "text": "Consona Corporation is a software company selling solutions to automate business critical tasks, ranging from marketing, service and support to planning and scheduling, material requirements planning (MRP), accounting, product configuration, and business intelligence.", "title": "" } ]	[ { "docid": "15428451", "text": "Zigurat was a Spanish software house for 8-bit home computers very popular in the eighties during the Golden Era of Spanish Software. Its origin is in the company Made in Spain, founded in 1983, which would know massive success in Spain with \"Fred\", commercialized in the United Kingdom as \"Roland on the Ropes\" (only the Amstrad CPC version). When the programmers and owners of Made in Spain could not go on alone on the task of distribution, they decided to create in 1986 another company, Zigurat, which would be entirely dedicated to distribution, and would distribute all the titles by Made in Spain, which became an internal producer seal under Zigurat. They would also distribute games by independent programmers or companies and would allow Made in Spain to concretate solely on programming. Later on, Made in Spain would completely merge into Zigurat, creating a single producer and distributor company. When the 8-bit market disappeared the company turned to develop games for arcade machines.", "title": "" }, { "docid": "27831325", "text": "Genieo Innovation is an Israeli company, specializing in unwanted software which includes advertising and user tracking software, commonly referred to as a \"potentially unwanted program\", \"adware\", \"privacy-invasive software\", \"grayware\", or \"malware\". They also own and operate InstallMac which distributes additional 'optional' search modifying software with other applications. In 2014, Genieo Innovation was acquired for $34 million by Somoto, another company which \"bundles legitimate applications with offers for additional third party applications that may be unwanted by the user\". This sector of the Israeli software industry is frequently referred to as Download Valley.", "title": "" }, { "docid": "6182328", "text": "Don H. Compier became Dean of the Bishop Kemper School for Ministry in Topeka, KS, in July 2014. BKSM is a joint project of the Episcopal Dioceses of Nebraska, Western Kansas, Kansas, and West Missouri. It uniquely seeks to educate candidates for ordained ministry, both priests and deacons, together with lay ministers. The school is strongly committed to making quality theological education affordable and accessible to all. Compier was ordained a priest in the Episcopal Church in January 2015.", "title": "" }, { "docid": "50114830", "text": "Bigben Interactive is a French company established in 1981 which designs and distributes video game and mobile phone accessories, distributes consumer electronics, and publishes and distributes video game software.", "title": "" }, { "docid": "212862", "text": "A software house is a company whose primary products are various forms of software, software technology, distribution, and software product development. Software houses are companies in the software industry.", "title": "" }, { "docid": "3852399", "text": "Brian Haberstroh is a businessman in New Hampshire who runs Distributed Mail Corporation, which once distributed software used to forward e-mail for other companies.", "title": "" }, { "docid": "6762676", "text": "Uniloc Corporation is a computer security and copy protection software company founded in Australia in 1992 that develops \"try and buy\" software distributed via magazines and preinstalled on new computers. It is best known for its controversial patent lawsuits which has led many to consider the company a \"patent troll\".", "title": "" }, { "docid": "24388074", "text": "Kivuto Solutions Inc., previously known as e-academy Inc., is a software distribution company that specializes in hosted electronic software delivery. Through its web-based solutions, the company offers a platform for institutions to distribute software according to their licensing requirements. Kivuto has partnerships with many software publishers including Microsoft, Adobe, VMware, National Instruments, and Parallels.", "title": "" }, { "docid": "8727412", "text": "FSA Corporation (formerly Freedman, Sharp, and Associates) developed UNIX and Windows system level software for security and distributed system administration in the 1990s. The company provided the underlying technology basis for software offerings by IBM, Symantec, and McAfee. FSA's best known products were its Load Balancer distributed workload management solution, its PowerBroker secure system administration solution for controlling and auditing the power of root on UNIX networks, and its CipherLink network encryption solution. The company was acquired by McAfee in 1996. The company was a testing ground for Theo de Raadt's ideas concerning open-source software, which led to the OpenBSD operating system. De Raadt was FSA's first non-founding employee.", "title": "" }, { "docid": "29580127", "text": "Software distribution is the process of delivering software to the end user. This is not to be confused with a \"distribution\", or \"distro\", which is collection of software components built, assembled and configured so that it can be used essentially \"as is\" for its intended purpose.", "title": "" }, { "docid": "34012278", "text": "Exact is a Dutch software company that offers accounting, ERP, and other software for small and medium enterprises. Exact develops cloud-based and on-premises software for industries such as accountancy, wholesale distribution, professional services and manufacturing, serving more than 350,000 companies.", "title": "" }, { "docid": "5389424", "text": "Arduino is an open source computer hardware and software company, project, and user community that designs and manufactures single-board microcontrollers and microcontroller kits for building digital devices and interactive objects that can sense and control objects in the physical world. The project's products are distributed as open-source hardware and software, which are licensed under the GNU Lesser General Public License (LGPL) or the GNU General Public License (GPL), permitting the manufacture of Arduino boards and software distribution by anyone. Arduino boards are available commercially in preassembled form, or as do-it-yourself kits.", "title": "" }, { "docid": "38262859", "text": "ScaleBase was a company that sold software to implement distributed MySQL databases for cloud computing. The software company was located in the Boston, Massachusetts, area.", "title": "" }, { "docid": "32651051", "text": "Broadbean is a recruitment software company based in London, England. The company develops software for the recruitment market, covering both in-house recruitment and staffing organisations, aimed at cutting costs & time from the recruitment process. Their main product is an automated job distribution tool that allows simultaneous job posting to multiple sites. The company also provides software tools to improve résumé/CV searches for recruiters, as well as a Facebook application providing search and application options for job-seekers. Broadbean's unique source-tracking technology records the origin of applications so users can establish which adverts and posting channels are responsible for the candidates they interview and hire.", "title": "" }, { "docid": "17817600", "text": "Soulfood Music Distribution GmbH is a German company distributing music and computer games (PC software and console) as well as related merchandise products. The company's distribution deals usually cover Germany, Austria and Switzerland (G/A/S). The headquarter of the company is located in Hamburg Germany.", "title": "" }, { "docid": "50701330", "text": "MailEnable is a Windows-based, commercial mail server distributed by MailEnable Pty. Ltd, an Australian-based software company which was established in 2002.", "title": "" }, { "docid": "1838103", "text": "Roxio, an American software company, specializes in developing consumer digital media products. Its product line includes tools for setting up digital media projects, media conversion software, and content distribution systems. The company formed as a spin-off of Adaptec's software division in 2001, and acquired MGI Software in 2002.", "title": "" }, { "docid": "21270193", "text": "A distributed workforce is a workforce that reaches beyond the restrictions of a traditional office environment. A distributed workforce is dispersed geographically over a wide area – domestically or internationally. By installing key technologies, distributed companies enable employees located anywhere to access all of the company’s resources and software such as applications, data and e-mail without working within the confines of a physical company-operated facility.", "title": "" }, { "docid": "2697339", "text": "SUSE ( ) is a German-based, multinational, open-source software company that develops and sells Linux products to business customers. Founded in 1992, it was the first company to market Linux for the enterprise. It is also the primary sponsor of the community-supported openSUSE Project which develops the openSUSE Linux distribution. The company is a wholly owned subsidiary of Micro Focus International.", "title": "" }, { "docid": "8174693", "text": "Software distributions, of which Linux distributions form a sizable proportion, are commonly referred to as \"distros\", with rolling release distributions commonly referred to as \"rolling distros\". When used as an adjective, instead of a noun, \"rolling release\" is often shortened to \"rolling\", when referring to distributions, software, or development models.", "title": "" }, { "docid": "1943822", "text": "Asianux is a Linux distribution. It is a joint development between Linux vendors Red Flag Software of China, Miracle Linux of Japan (50.5-percent owned by Oracle Corporation), Hancom of South Korea, VietSoftware of Vietnam (from September 2007), WTEC from Thailand (from December 2008) and Enterprise Technology (Pvt) Limited of Sri Lanka (from July 2010). It is distributed and marketed by Red Flag Software and Miracle. Asianux is designed as a core component or basis for a Linux distribution, which would be released by related companies as their own distributions with distinct features. Localized languages include Chinese, Japanese, Korean and English. Comparisons have been drawn between Asianux and United Linux, an attempt by SUSE, Turbolinux, Conectiva and the SCO Group to take on Red Hat Enterprise Linux.", "title": "" }, { "docid": "44674463", "text": "RamBase is a Norwegian fully integrated cloud ERP system, web-based (SaaS). It is a business software solution for manufacturing, distribution auction and e-commerce organizations which covers the whole value chain from sales to production and delivery. RamBase software products targeted at large, mid-sized and small companies. Headquartered in Nedre Vats in Norway.", "title": "" }, { "docid": "13689443", "text": "JDA Software Group, Inc. is an American software and consultancy company (owned by New Mountain Capital), providing supply chain management, manufacturing planning, retail planning, store operations and collaborative category management solutions headquartered in Scottsdale, Arizona. The company has more than 4,000 companies as customers in the manufacturing, distribution, transportation, retail and services industries. Subsidiary companies include RedPrairie, i2 Technologies, Manugistics, E3, Intactix, and Arthur.", "title": "" }, { "docid": "2848768", "text": "Intertrust Technologies Corporation is a software technology company specializing in trusted distributed computing. Much of Intertrust's digital rights management (DRM) business is based on the Marlin DRM technology, which Intertrust founded along with four consumer electronics companies: Sony, Panasonic, Philips, and Samsung.", "title": "" }, { "docid": "1660841", "text": "Distribution software refers to software which manages everything from order processing and inventory control to accounting, purchasing and customer service, supply chain management, sales, customer relationship management, and finance management.", "title": "" }, { "docid": "368176", "text": "Ambrosia Software is a predominantly Macintosh software company located in Rochester, New York, U.S. Ambrosia produces utility software and video games. Its products are distributed as shareware; demo versions can be downloaded and used for up to 30 days.", "title": "" }, { "docid": "45062283", "text": "Kinetica DB, Inc. is a company that develops a distributed, in-memory database management system using graphics processing units (GPUs). The software it markets is also called Kinetica. The company has headquarters in Arlington, Virginia and San Francisco.", "title": "" }, { "docid": "22821276", "text": "KOAN is an Italian company (also known as Koan Software) originally oriented in software for industrial automation since its founding in 1996, and subsequently specialized in embedded software. Currently it is mostly focusing on Embedded Linux distribution KaeilOS, Linux device driver development, embedded software consulting and Linux real time operating system integration with Xenomai and RTAI. KOAN head office are located in Bergamo, Italy.", "title": "" }, { "docid": "33185688", "text": "Xpert-Design Software is a software development company based in Stadtbergen, Germany. Xpert-Design Software develops and distributes Xpert-Timer Enterprise, Pro, Xpert-Timer Basic and Xpert-Timer Mobile.", "title": "" }, { "docid": "29372337", "text": "Koramgame is a subsidiary of Koram Games Limited, which is the Kunlun Group's Hong Kong subsidiary company. The company has published many of Kunlun's games in English, French, Spanish, German. In Russian versions of the games the company approved the rules to unqualified people and works out of law. Kunlun Group is an international company based in Beijing that specializes in browser- based game development, software distribution, and other internet services.", "title": "" } ]
9568	Is 'days to cover' a useful metric in identifying the potential for a short squeeze?	[ { "docid": "369437", "text": "SeekingAlpha has an article about short squeezes that states: The higher the number of days to cover means the possibility for a short squeeze is greater, and the potential size of the short squeeze is also greater Logically, this makes sense. A short squeeze occurs when a lack of supply meets excess demand for a stock, so the potential for a squeeze increases when supply and demand begin to get out of equilibrium. Think of two things that would cause the days to cover to increase and what effect they would have on supply and demand. The current short interest (numerator) increases. This implies that if some event triggers short sellers to cover their position, there are a higher number of short sellers who will need to do so. This heightens the chances that demand will exceed supply. The average daily volume (denominator) decreases. This implies that fewer investors are trading the stock, so if an event triggers short sellers to cover their positions, there might not be enough traders in the market willing to sell their shares. (Obviously, if a short-squeeze occurs, volume may increase because traders who were unwilling to sell their shares become willing).", "title": "" } ]	[ { "docid": "107045", "text": "Rich's answer captures the basic essence of short selling with example. I'd like to add these additional points: You typically need a specially-privileged brokerage account to perform short selling. If you didn't request short selling when you opened your account, odds are good you don't have it, and that's good because it's not something most people should ever consider doing. Short selling is an advanced trading strategy. Be sure you truly grok selling short before doing it. Consider that when buying stock (a.k.a. going long or taking a long position, in contrast to short) then your potential loss as a buyer is limited (i.e. stock goes to zero) and your potential gain unlimited (stock keeps going up, if you're lucky!) Whereas, with short selling, it's reversed: Your loss can be unlimited (stock keeps going up, if you're unlucky!) and your potential gain is limited (i.e. stock goes to zero.) The proceeds you receive from a short sale – and then some – need to stay in your account to offset the short position. Brokers require this. Typically, margin equivalent to 150% the market value of the shares sold short must be maintained in the account while the short position is open. The owner of the borrowed shares is still expecting his dividends, if any. You are responsible for covering the cost of those dividends out of your own pocket. To close or cover your short position, you initiate a buy to cover. This is simply a buy order with the intention that it will close out your matching short position. You may be forced to cover your short position before you want to and when it is to your disadvantage! Even if you have sufficient margin available to cover your short, there are cases when lenders need their shares back. If too many short sellers are forced to close out positions at the same time, they push up demand for the stock, increasing price and deepening their losses. When this happens, it's called a short squeeze. In the eyes of the public who mostly go long buying stock, short sellers are often reviled. However, some people and many short sellers believe they are providing balance to the market and preventing it sometimes from getting ahead of itself. [Disambiguation: A short sale in the stock market is not related to the real estate concept of a short sale, which is when a property owner sells his property for less than he owes the bank.] Additional references:", "title": "" }, { "docid": "397325", "text": "\"To summarize, there are three basic ways: (3) is the truly dangerous one. If there is a lot of short interest in a stock, but for some reason the stock goes up, suddenly a lot of people will be scrambling to buy that stock to cover their short position -- which will drive the price up even further, making the problem worse. Pretty soon, a bunch of smart rich guys will be poor guys who are suddenly very aware that they aren't as smart as they thought they were. Eight years ago, such a \"\"short squeeze\"\", as it's called, made the price of VW quadruple in two days. You could hear the Heinies howl from Hamburg to Haldenwanger. There are ways to protect yourself, of course. You can go short but also buy a call at a much higher price, thereby limiting your exposure, a strategy called a \"\"straddle\"\", but you also reduce your profit if you guessed right. It comes down to, as it always does, do you want to eat well, or to sleep well?\"", "title": "" }, { "docid": "352346", "text": "What are Pivot Points? Pivot Points indicate price levels that are of significance in technical analysis of securities. Pivot Points are used to provide clarity for a trader as they are a predictive indicator of where a security might go. There are at least 6 different types of Pivot Points (Woodie Pivot Point, Fibonacci Pivot, Demark etc..) and they are different based on their formulas but generally serve the same concept. I will be answering your question using the Camarilla Pivot Point formula. Camarilla Pivot Point Formula Generally any Pivot Point formula uses a combination of the Open, High, Low and Close of the previous timeframe. Since you are technically a swing trader indicated by say between a couple of days to a couple of weeks, as I don't want to do day trading you should use a weekly 5 to 30 minute chart but you can also use a daily chart as well. So for example if you use a daily chart, you would use the Open, High, Low and Close of the previous day. Example of fictitious stock: MOSEX (Money Stack Exchange) 01/14/16: Open: 10.25, High: 12.55, Low: 9.65, Close: 11.50 On 01/15/16: R4 Level: 13.10, R3 Level: 12.30, R2 Level: 12.03, R1 Level: 11.77, Pivot Point: 11.23, S1 Level: 11.23, S2 Level: 10.97, S3 Level: 10.70, S4 Level: 9.91 R = Resistance, S = Support How to identify these Pivot Points? Most charting software already have built in overlays that will identify the pivot points for you but you can always find and draw them yourself with an annotation tool. Since we are using the Camarilla Pivot Point formula, the important Pivot Point levels are the R4 which is considered as the Breakout Pivot, the S4 which is considered as the Breakdown Pivot. R3 and S3 are Reversal Pivot Points. Once identify the Pivot Points how should you proceed in a trade? This is the million dollar question and without spoon feeding you requires you to come up with your own strategy. To distinguish yourself from being a novice and pro trader is to have a strategy in a trade. Now I don't really have the time to look for actual charts to provide examples with but generally this is what you should look for to proceed in a trade: Potential Buy/Short Signals: Potential Sell Signals: If a stock moves above the R3 Level but then crosses below it, this would be a sell signal. This is confirmed when their is a lower lower then the candle that first crosses below it. Sell a stock when S4 Level is confirmed. See above for the confirmation. Other Useful Tips: Use the Pivot Point as your support or resistance. The Pivot Point levels can be used for your stop loss. For example, with an S3 reversal buy signal, the S4 should be used as a stop loss. Conversely, the Pivot Point levels can also be used for your target prices. For example, with an S3 reversal buy signal, you should take some profits at R3 level. You should also use a combination of other indicators to give you more information to confirm if a signal is correct. Examples of a good combination is the RSI, MACD and Moving Averages. Read that book in my comment above!!", "title": "" }, { "docid": "553110", "text": "\"There are situations where you can be forced to cover a position, particular when \"\"Reg SHO\"\" (\"\"regulation sho\"\") is activated. Reg SHO is intended to make naked short sellers cover their position, it is to prevent abusive failure to delivers, where someone goes short without borrowing someone else's shares. Naked shorting isn't a violation of federal securities laws but it becomes an accounting problem when multiple people have claims to the same underlying assets. (I've seen companies that had 120% of their shares sold short, too funny, FWIW the market was correct as the company was worth nothing.) You can be naked short without knowing it. So there can be times when you will be forced to cover. Other people being forced to cover can result in a short squeeze. A risk. The other downside is that you have to pay interest on your borrowings. You also have to pay the dividends to the owner of the shares, if applicable. In shorter time frames these are negligible, but in longer time frames, such as closer to a year or longer, these really add up. Let alone the costs of the market going in the opposite direction, and the commissions.\"", "title": "" }, { "docid": "117576", "text": "\"A stock split can force short sellers of penny stocks to cover their shorts and cauuse the price to appreciate. Example: Someone shorts a worthless pump and dump stock, 10,000 shares at .50. They have to put up $25,000.00 in margin ($2.50 per share for stocks under $2.50). The company announces a 3 to 1 split. Now the short investor must come up with $50,000.00 additional margin or be be \"\"bought in\"\". The short squeeze is on.\"", "title": "" }, { "docid": "295511", "text": "When you buy a stock, the worst case scenario is that it drops to 0. Therefore, the most you can lose when buying a stock is 100% of your investment. When you short a stock, however, there's no limit on how high the stock can go. If you short a stock at 10, and it goes up to 30, then you've lost 200% on your investment. Therefore shorting stocks is riskier than buying stocks, since you can lose more than 100% of your investment when shorting. because the price might go up, but it will never be as big of a change as a regular price drop i suppose... That is not true. Stocks can sometimes go up significantly (50-100% or more) in a very short amount of time on a positive news release (such as an earnings or a buyout announcement). A famous example occurred in 2008, when Volkswagen stock quintupled (went up 400%) in less than 2 days on some corporate news: Porsche, for some reason, wants to control Volkswagen, and by building up its stake has driven up the price. Hedge funds, figuring the share price would fall as soon as Porsche got control and stopped buying, sold a lot of VW shares short. Then last weekend, Porsche disclosed that it owned 42.6 percent of the stock and had acquired options for another 31.5 percent. It said it wanted to go to 75 percent. The result: instant short-squeeze. The German state of Lower Saxony owns a 20 percent stake in VW, which it said it would not sell. That left precious few shares available for anyone else. The shorts scrambled to cover, and the price leaped from about €200, or about $265, to above €1,000.", "title": "" }, { "docid": "273142", "text": "\"I would think that a lot of brokers would put the restriction suggested in @homer150mw in place or something more restrictive, so that's the first line of answer. If you did get assigned on your short option, then (I think) the T+3 settlement rules would matter for you. Basically you have 3 days to deliver. You'll get a note from your broker demanding that you provide the stock and probably threatening to liquidate assets in your account to cover their costs if you don't comply. If you still have the long-leg of the calendar spread then you can obtain the stock by exercising your long call, or, if you have sufficient funds available, you can just buy the stock and keep your long call. (If you're planning to exercise the long call to cover the position, then you need to check with your broker to see how quickly the stock so-obtained will get credited to your account since it also has some settlement timeline. It's possible that you may not be able to get the stock quickly enough, especially if you act on day 3.) Note that this is why you must buy the call with the far date. It is your \"\"insurance\"\" against a big move against you and getting assigned on your short call at a price that you cannot cover. With the IRA, you have some additional concerns over regular cash account - Namely you cannot freely contribute new cash any time that you want. That means that you have to have some coherent strategy in place here that ensures you can cover your obligations no matter what scenario unfolds. Usually brokers put additional restrictions on trades within IRAs just for this reason. Finally, in the cash account and assuming that you are assigned on your short call, you could potentially could get hit with a good faith, cash liquidation, or free riding violation when your short call is assigned, depending on how you deliver the stock and other things that you're doing in the same account. There are other questions on that on this site and lots of information online. The rules aren't super-simple, so I won't try to reproduce them here. Some related questions to those rules: An external reference also on potential violations in a cash account: https://www.fidelity.com/learning-center/trading-investing/trading/avoiding-cash-trading-violations\"", "title": "" }, { "docid": "327814", "text": "First utilize a security screener to identify the security profiles you are looking to identify for identifying your target securities for shorting. Most online brokers have stock screeners that you can utilize. At this point you may want to look at your target list of securities to find out those that are eligible for shorting. The SHO thresold list is also a good place to look for securities that are hard to borrow to eliminate potential target securities. http://regsho.finra.org/regsho-Index.html Also your broker can let you know the stocks that are available for borrowing. You can then take your target securities and then you can look at the corporate filings on the SEC's Edgar site to look for the key words you are looking for. I would suggest that you utilize XBRL so you can electronically run your key word searched in an automated manner. I would further suggest that you can run the key word XBRL daily for issuer filings of your target list of securities. Additional word searches you may want to consider are those that could indicate a dilution of the companies stock such as the issuance of convertible debt. Also the below link detailing real short interest may be helpful. Clearing firms are required to report short interest every two weeks. http://www.nasdaq.com/quotes/short-interest.aspx", "title": "" }, { "docid": "577585", "text": "Pivots Points are significant levels technical analysts can use to determine directional movement, support and resistance. Pivot Points use the prior period's high, low and close to formulate future support and resistance. In this regard, Pivot Points are predictive or leading indicators. There are at least five different versions of Pivot Points. I will focus on Standard Pivot Points here as they are the simplest. If you are looking to trade off daily charts you would work out your Pivot Points from the prior month's data. For example, Pivot Points for first trading day of February would be based on the high, low and close for January. They remain the same for the entire month of February. New Pivot Points would then be calculated on the first trading day of March using the high, low and close for February. To work out the Standard Pivot Points you use the High, Low and Close from the previous period (i.e. for daily charts it would be from the previous month) in the following formulas: You will now have 5 horizontal lines: P, R1, R2, S1 and S2 which will set the general tone for price action over the next month. A move above the Pivot Point P suggests strength with a target to the first resistance R1. A break above first resistance shows even more strength with a target to the second resistance level R2. The converse is true on the downside. A move below the Pivot Point P suggests weakness with a target to the first support level S1. A break below the first support level shows even more weakness with a target to the second support level S2. The second resistance and support levels (R2 & S2) can also be used to identify potentially overbought and oversold situations. A move above the second resistance level R2 would show strength, but it would also indicate an overbought situation that could give way to a pullback. Similarly, a move below the second support level S2 would show weakness, but would also suggest a short-term oversold condition that could give way to a bounce. This could be used together with a momentum indicator such as RSI or Stochastic to confirm overbought or oversold conditions. Pivot Points offer a methodology to determine price direction and then set support and resistance levels, however, it is important to confirm Pivot Point signals with other technical analysis indicators, such as candle stick reversal patterns, stochastic and general Support and Resistance Levels in the price action. These pivot points can be handy but I actually haven’t used them for trade setups and entries myself. I prefer to use candle sticks together with stochastic to determine potential turning points and then take out trades based on these. You can then use the Pivot Points Resistance and Support levels to help you estimate profit targets or areas to start becoming cautious and start tightening your stops. Say, for example, you have gone long from a signal you got a few days ago, you are now in profit and the price is now approaching R2 whilst the Stochastic is approaching overbought, you might want to start tightening your stop loss as you might expect some weakness in the price in the near future. If prices continue up you keep increasing your profits, if prices do reverse then you keep the majority of your existing profits. This would become part of your trade management. If you are after finding potential market turning points and take out trades based on these, then I would suggest using candlestick charting reversal patterns for your trade setups. The patterns I like to use most in my trading can be described as either the Hammer or One White Soldier for Bullish reversals and Shooting Star or One Black Crow for Bearish reversals. Below are diagrams of where to place your entries and exits on both Bullish and Bearish reversal patterns. Bullish Reversal Pattern So after some period of weakness in the price you would look for a bullish day where the price closes above the previous day’s high, you place your buy order here just before market close and place your initial stop just below the low of the day. You would apply this either for an uptrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the support line. The trade is reinforced if the Stochastic is in or near the oversold and crossing back upwards, volume on the up day is higher than volume on the down days, and the market as a whole is moving up as well. The benefit with this entry is that you are in early so you capture any bullish move up at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves up you would move your stop loss to just below the low of each day. Alternative Bullish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop buy order to buy at the open of next trading day just above the high of the bullish green candle. Your stop is placed exactly the same, just below the low of the green bullish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bullish news prior to and at the next open, so miss out on some potential profits if prices do gap up at the open. This may also increase your loss on the trade if the prices gaps up then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. Bearish Reversal Pattern So after some short period of strength in the price you would look for a bearish day where the price closes below the previous day’s low, you place your sell short order here just before market close and place your initial stop just above the high of the day. You would apply this either for an downtrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the resistance line. The trade is reinforced if the Stochastic is in or near the overbought and crossing back downwards, volume on the up day is higher than volume on the up days, and the market as a whole is moving down as well. The benefit with this entry is that you are in early so you capture any bearish move down at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves down you would move your stop loss to just above the high of each day. Alternative Bearish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop sell short order to sell at the open of next trading day just below the low of the bearish red candle. Your stop is placed exactly the same, just above the high of the red bearish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bearish news prior to and at the next open, so miss out on some potential profits if prices do gap down at the open. This may also increase your loss on the trade if the prices gaps down then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. You could also trade other candle stick patterns is similar ways. And with the long entries you can also use them to get into the market with longer term trend following strategies, you would usually just use a larger stop for longer term trading. To determine the size of your order you would use the price difference between your entry and your stop. You should not be risking more than 1% of your trading capital on any one trade. So if your trading capital is $20,000 your risk per trade should be $200. If you were looking to place your buy at 5.00 and had your initial stop at $4.60, you would divide $200 by $0.40 to get 500 stocks to buy. Using this form of money management you keep your losses down to a maximum of $200 (some trades may be a bit higher due to some slippage which you should allow for in your trading plan), which becomes your R-multiple. Your aim is to have your average win at 3R or higher (3 x your average loss), which will give you a positive expectancy even with a win ratio under 50%. Once you have written down your trading rules you can search stock charts for potential setups. When you find one you can backtest the chart for similar setup over the past few years. For each setup in the past jot down the prices you would have entered at, where you would have set your stop, work out your R, and go day by day, moving your stop as you go, and see where you would have been stopped out. Work out your profit or loss in terms of R for each setup and then add them up. If you get a positive R multiple, then this may be a good stock to trade on this setup. If you get a negative R multiple, then maybe give this stock a miss and look for the next setup. You can setup watch-lists of stocks that perform well for both long setups and short setups, and then trade these stocks when you get a new signal. It can take some time starting off, but once you have got your watch-lists for a particular setup, you just need to keep monitoring those stocks. You can create other watch-lists for other type of setups you have backtested as well.", "title": "" }, { "docid": "468455", "text": "5.3% counts as junk these days? Wow, I miss the 13 - 22% days :-). Certainly shows a lot of confidence in Teslas ability to produce Model 3's. It also is going to squeeze the short sellers a bit harder as the capital is going to push out their 'dead by' dates. I feel no pity for them.", "title": "" }, { "docid": "302310", "text": "\"The only thing worse than finding out you are paid less than a co-worker is finding out that you are paid more than all of your co-workers. A lot of people who think they would prefer an open and transparent pay-scale (as in unions), change their minds, when placed in one. I have worked in and implemented both types, as both an employee and as an owner/manager. There are pluses and minuses to both. - \"\"Transparent\"\" pay-scale is most effective in a high-turnover, aggressively performance-metric-oriented environment where you expect people to be competing for jobs, including their own job, every day. For example, a pool of commissioned sales-agents: the more you sell, the more you make. Winner gets a Cadillac. Runner-up gets a set of steak knives. Loser gets fired, that kind of thing. If you can't meet your numbers, we let other people start poaching your territory/clients and see what they can do. - Where it doesn't work is in a salary-type position where people are expected to have multiple \"\"soft\"\" duties outside of core performance metrics. The reasons are multi-fold: - One immediate effect of implementing performance-based pay for salary-type employees is that people who are in the office for 8 hours a day, five days a week, immediate start devoting their time and energy towards getting another notch up on the pay-scale, even at the expense of their co-workers, or the company. It intrinsically incentivizes \"\"gaming the system\"\", finding ways to attach your name to easy metrics, and to remove yourself from the most difficult problems. The people who are best at hitting metrics are often not even close to the MVPs. - If instead you take a \"\"soft metrics\"\" or subjective/holistic approach to evaluation, then you get a culture of brown-nosing and office-politics. People start sabotaging the \"\"boss's favorite\"\" and pursuing approval and credit, rather than performance. Instead of fostering a team-oriented, problem-solving approach, it fosters a counter-productive buck-passing, credit-grabbing, and blame-avoidance approach. Note that both of the above intrinsically incentivize risk-avoidance. If you get paid for the number of projects that have your name on them, you find some way to get your name attached to every project, and then move on to the next one, whether the last one was done or not. If you get based on how \"\"successful\"\" the projects bearing your name are, then you avoid anything challenging and make sure only to be attached to the easy ones with the best co-workers. And so on. - Alternately, let's say we keep the same, generic, salary-oriented pay-structure, we just make everyone in a certain \"\"tier\"\" get equal salary, that everyone knows. That sucks all the life out of everyone's sails so fast it will make your head spin: you cannot get a raise for doing a better job, you get paid the same raise as your worst co-worker, every year, for as long as you work here. We will never cut your pay, all you have to do is not be the canary in the coalmine-- so long as you can identify the worst performer in your group, and so long as it's not you, your job is safe. What time do you have to arrive? 5 minutes earlier than the latest-arriving person. How early can you leave? 5 minutes after the earliest one to check out. How much work do you have to get done? Only as much as anyone else is doing. What will you get for being the hardest-working, earliest-to-arrive, latest-to-leave? The same as the worst performer gets: you'll be splitting your raise with him, since we don't credit individuals here, just job-titles. Most jobs that can be easily automated, are automated. If you need a human employee to do it, it's usually because it involves a nontrivial amount of \"\"soft\"\" skills and fuzzy-logic type thinking and behavior. A machine programmed purely to make as many widgets per hour as possible, and motivated to so with human-style skills, ingenuity, and incentives, will tear down the whole factory and dismantle all its co-workers and ignore all quality-controls in order to keep producing widgets. You can't reduce human beings to input-process-output flowcharts (or rather you can, but they will invariably find unintended ways to outsmart your design criteria, with unintended consequences). The reason you need a person instead of an automated process is because you need a whole host hard-to-define, soft/fuzzy/flexible critical-thinking type skills. Everyone's job seems easier to the people who don't have to do it, and there is a tremendous hidden danger to de-valuing personal desire to do a subjectively \"\"good job\"\" by quantifying/genericizing the value of their contribution. Personnel management is very difficult to reduce to an engineering problem. You usually need good managers who can identify and motivate good employees, who will feel lucky to have the job and the salary they have, and who will come in every day trying to earn it. Posting everyone's pay on a bulletin-board negates all those \"\"soft\"\" skills, by putting a quantified, black-and-white, relative value on everyone's contribution. Even in a very large organization, the \"\"marketplace\"\" of employees is rarely large enough, and the quality of real-time metrics is almost never good enough to \"\"digitize\"\" the bell-curve of employee performance. You end up making it a square-wave that demotivates all but the most extreme outliers.\"", "title": "" }, { "docid": "345368", "text": "\"If you sell a stock you don't own, it's called a short sale. You borrowed the shares from an owner of the stock and eventually would buy to close. On most normal shares, you can hold a short position indefinitely, but there are some shares that have a combination of either a small float or too high a short position that shares to short are not available. This can create a \"\"short squeeze\"\" where shorts are burned by being forced to buy the stock back. Last - when you did this, you should have instructed the broker that you were \"\"selling to open\"\" or \"\"selling short.\"\" In the old days, when people held stock certificates, you were required to send the certificate in when you sold. Today, the broker should know that wasn't your intention.\"", "title": "" }, { "docid": "226984", "text": "\"The settlement date for any trade is the date on which the seller gets the buyer's money and the buyer gets the seller's product. In US equities markets the settlement date is (almost universally) three trading days after the trade date. This settlement period gives the exchanges, the clearing houses, and the brokers time to figure out how many shares and how many dollars need to actually be moved around in order to give everyone what they're owed (and then to actually do all that moving around). So, \"\"settling\"\" a short trade is the same thing as settling any other trade. It has nothing to do with \"\"closing\"\" (or covering) the seller's short position. Q: Is this referring to when a short is initiated, or closed? A: Initiated. If you initiate a short position by selling borrowed shares on day 1, then settlement occurs on day 4. (Regardless of whether your short position is still open or has been closed.) Q: All open shorts which are still open by the settlement date have to be reported by the due date. A: Not exactly. The requirement is that all short positions evaluated based on their settlement dates (rather than their trade dates) still open on the deadline have to be reported by the due date. You sell short 100 AAPL on day 1. You then cover that short by buying 100 AAPL on day 2. As far as the clearing houses and brokers are concerned, however, you don't even get into the short position until your sell settles at the end of day 4, and you finally get out of your short position (in their eyes) when your buy settles at the end of day 5. So imagine the following scenarios: The NASDAQ deadline happens to be the end of day 2. Since your (FINRA member) broker has been told to report based on settlement date, it would report no open position for you in AAPL even though you executed a trade to sell on day 1. The NASDAQ deadline happens to be the end of day 3. Your sell still has not settled, so there's still no open position to report for you. The NASDAQ deadline happens to be the end of day 4. Your sell has settled but your buy has not, so the broker reports a 100 share open short position for you. The NASDAQ deadline happens to be the end of day 5. Your sell and buy have both settled, so the broker once again has no open position to report for you. So, the point is that when dealing with settlement dates you just pretend the world is 3 days behind where it actually is.\"", "title": "" }, { "docid": "61853", "text": "\"But what happen if the stock price went high and then go down near expiry date? When you hold a short (sold) call option position that has an underlying price that is increasing, what will happen (in general) is that your net margin requirements will increase day by day. Thus, you will be required to put up more money as margin to finance your position. Margin money is simply a \"\"good faith\"\" deposit held by your broker. It is not money that is debited as cash from the accounting ledger of your trading account, but is held by your broker to cover any potential losses that may arise when you finally settle you position. Conversely, when the underlying share price is decreasing, the net margin requirements will tend to decrease day by day. (Net margin is the net of \"\"Initial Margin\"\" and \"\"Variation Margin\"\".) As the expiry date approaches, the \"\"time value\"\" component of the option price will be decreasing.\"", "title": "" }, { "docid": "148270", "text": "The Art of Short Selling by Kathryn Stanley providers for many case studies about what kind of opportunities to look for from a fundamental analysis perspective. Typically things you can look for are financing terms that are not very favorable (expensive interest payments) as well as other constrictions on cash flow, arbitrary decisions by management (poor management), and dilution that doesn't make sense (usually another product of poor management). From a quantitative analysis perspective, you can gain insight by looking at the credit default swap rate history, if the company is listed in that market. The things that affect a CDS spread are different than what immediately affects share prices. Some market participants trade DOOMs over Credit Default Swaps, when they are betting on a company's insolvency. But looking at large trades in the options market isn't indicative of anything on its own, but you can use that information to help confirm your opinion. You can certainly jump on a trend using bad headlines, but typically by the time it is headline news, the majority of the downward move in the share price has already happened, or the stock opened lower because the news came outside of market hours. You have to factor in the short interest of the company, if the short interest is high then it will be very easy to squeeze the shorts resulting in a rally of share prices, the opposite of what you want. A short squeeze doesn't change the fundamental or quantitative reasons you wanted to short. The technical analysis should only be used to help you decide your entry and exit price ranges amongst an otherwise random walk. The technical rules you created sound like something a very basic program or stock screener might be able to follow, but it doesn't tell you anything, you will have to do research in the company's public filings yourself.", "title": "" }, { "docid": "23488", "text": "I'm old. When I was young, the schools were preparing us all for the Metric System. But the change never happened, due, I believe, to simple arrogance. Let the world cope with out 45/17th nuts and bolts. Now of course, we're not so powerful and I do assume that American Toyota factories use metric parts. I write this from a metric coffee house in Amsterdam. I am coping quite well with their products offered metrically. Have a good day!", "title": "" }, { "docid": "48153", "text": "Yes you can. This is known as a short selling against the box. In the old days, this was used to delay a taxable event. You could lock in a gain without triggering a taxable event. Any loss on one side of the box would be offset by a loss on the other side, and vice versa. However, the IRS clamped down on this, and you will realize the gain on your long position as soon as you go short on the other side. See http://www.investopedia.com/terms/s/sellagainstthebox.asp. As to how to initiate the short cover, just transfer the long position to the same account as your short position and make sure your broker covers the short. Should be relatively easy.", "title": "" }, { "docid": "76523", "text": "I think you are addressing it the wrong way around. Insurance - in its basic idea - is supposed to protect you from exceptional and potentially life-changing financial situations; not from day-to-day cost. That means that covering the first 1000 $ is pretty much useless; for any serious sickness the insurance would be without merit. For example, it makes sense to insure your house against fire; the premium is small compared to the potential damage, which works because the chance of a fire is also small. If you extend a fire insurance to cover dropped glasses, or broken TV sets, it becomes quickly a bad idea - chances for these events are higher, so insurance cost go up (and the events are easier to fake too). Insurance should cover the large damage with low risk, never the small damage with more risk. The only reason the latter exist is that people don't understand it, and insurances make money on it, so they offer it. Apply this to your insurance idea, and the right way would be: Pay 50 $ to cover any cost over 10000 $; Pay 100$ to cover any cost over 5000 $; Pay 200 $ to cover any cost over 2500 $; And so on (all numbers are taken from thin air as an example). I would love if there is an relatively cheap insurance that covers anything above 10000 $ (or even a higher threshold); they don't exist because there is not enough money to make for insurance companies.", "title": "" }, { "docid": "73172", "text": "I think it already came in 2008. An arbitrary definition of GDP growth hardly means we aren't in a recession now. Numberous metrics were used to identify recessions and we aren't out of woods just because the most widely accepted definition says we are doing mildly better. Any illusions of recovery are created by stimulus spending. When we run out of those bullets we are fucked again unless we have real solutions before then.", "title": "" }, { "docid": "77570", "text": "First of all, a person that relies on their ability to tap a line of credit to cover an emergency isn't generally the kind of person that has investments they can cash out to cover the debt. That being said, my personal reasons for having a liquid emergency fund revolve around bank errors and identify theft. I used to work for a company that made bank software. Errors are a common occurrence. You'd be surprised how many transactions are still input by human hands despite our computerized world. All it takes is one typo to wipe out your ability to swipe plastic for a few days. This has actually happened to me. My utility company sent me a bill for $240 and wound up taking $2400 by accident, overdrawing my account and sending me into a fee spiral. They fixed their mistake... several days later. The snowball of fees from other transactions that bounced took another two months to correct. In the meantime, I also had my mortgage payment due. In the US, you can't pay your mortgage with credit, and for those who rent, many landlords won't let you pay with credit either. I have also seen this scenario play out twice with other people I've known who've had their ID stolen. Yes, the bank will cover the fraud after a lengthy process. But the disruption causes fees and overdrafts to quickly snowball out of control. I have a separate savings account at a different bank for this kind of thing, and I have a few hundred dollars cash in my house at all times. Having a liquid emergency fund allows you to quickly stabilize the situation and gives you walking around money for those times where the banking system becomes your enemy for a time.", "title": "" }, { "docid": "49794", "text": "I'm just began playing in the stock market. I assume you mean that you're not using real money, but rather you have an account with a stock simulator like the one Investopedia offers. I am hopeful that's the case due to the high level of risk involved in short selling like you're describing. Here is another post about short selling that expands a bit on that point. To learn much more about the ins and outs of short selling I will point again to Investopedia. I swear I don't work for them, but they do have a great short selling tutorial. When you short sell a stock you are borrowing the stock from your broker. (The broker typically uses stock held by one or more of his clients to cover the loan.) Since it's basically a loan you pay interest. Of course the longer you hold it the more interest you pay. Also, as Joe mentioned there are scenarios in which you may be forced to buy the stock (at a higher price than you sold it). This tends to happen when the stock price is going against the short sell (i.e. you lose money). Finally, did anyone mention that the potential losses in a short sell are infinite?", "title": "" }, { "docid": "265533", "text": "Probably means cutting the travel short. A small business owner employing specialist staff needs to identify and plan for this risk. The plan might be to personally cover for the staff until a replacement is found. Ideally in this situation the business will be able to support the salary of two staff in the role, even if one is part time or an apprentice/trainee. This is the approach our business takes with key staff.", "title": "" }, { "docid": "329662", "text": "\"As the other answer said, the person who owns the lent stock does not benefit directly. They may benefit indirectly in that brokers can use the short lending profits to reduce their fees or in that they have the option to short other stocks at the same terms. Follow-up question: what prevents the broker lending the shares for a very short time (less than a day), pocketing the interest and returning the lenders their shares without much change in share price (because borrowing period was very short). What prevents them from doing that many times a day ? Lack of market. Short selling for short periods of time isn't so common as to allow for \"\"many\"\" times a day. Some day traders may do it occasionally, but I don't know that it would be a reliable business model to supply them. If there are enough people interested in shorting the stock, they will probably want to hold onto it long enough for the anticipated movement to happen. There are transaction costs here. Both fees for trading at all and the extra charges for short sale borrowing and interest. Most stocks do not move down by large enough amounts \"\"many\"\" times a day. Their fluctuations are smaller. If the stock doesn't move enough to cover the transaction fees, then that seller lost money overall. Over time, sellers like that will stop trading, as they will lose all their money. All that said, there are no legal blocks to loaning the stock out many times, just practical ones. If a stock was varying wildly for some bizarre reason, it could happen.\"", "title": "" }, { "docid": "458907", "text": "\"If you can't find anyone to lend you the shares, then you can't short. You can attempt to raise the interest rate at which you will borrow at, in order to entice others to lend you their shares. In practice, broadcasting this information is pretty convoluted. If there aren't any stocks for you to buy back, then you have to buy back at a higher price. As in, place a limit buy order higher and higher until someone decides to sell to you. This affects your profit. Regarding the public ledger: This functions different in different markets. United States stock markets have an evolving body of regulations to alleviate the exact concerns you detailed, but Canada's or Dubai's stock markets would have different provisions. You make the assumption that it is an efficient process, but it is not and it is indeed ripe for abuse. In US stocks, the public ledger has a 3 business day delay between showing change of ownership. Many times brokers and clearing firms and other market participants allow a customer to go short with fake shares, with the idea that they will find real shares within the 3 business day time period to cover the position. During the time period that there is no real shares hitting the market, this is called a \"\"naked short\"\". The only legal system that attempts to deter this practice is the \"\"fail to deliver\"\" (FTD) list. If someone fails to deliver, that means there is a short position active with fake shares for which no real shares have been borrowed against. Too many FTD's allow for a short selling restriction to be placed, meaning nobody else can be short, and existing short sellers may be forced to cover.\"", "title": "" }, { "docid": "537418", "text": "\"Vitalik has mentioned this in a comment but I think it ought to be expanded upon: Companies that aren't already penny stocks really don't stand to gain anything from trying to prevent short interest. Short selling does not inherently lower the stock price - not any more so than any other kind of selling. When somebody shorts a stock, it's simply borrowed from another investor's margin; as long as it's not a naked short resulting in an FTD (Failure To Deliver) then it does not add any \"\"artificial\"\" selling pressure. In fact, shorting can actually drive the price up in the long term due to stops and margin calls. Not a guarantee, of course, but if a rally occurs then a high short interest can cause a cascade effect from the short \"\"squeeze\"\", resulting in an even bigger rally than what would have occurred with zero short interest. Many investors actually treat a high short interest as a bullish signal. Compare with margin buying - essentially the opposite of short selling - which has the opposite effect. If investors buy stocks on margin, then if the value of that stock decreases too rapidly they will be forced to sell, which can cause the exact same cascade effect as a short interest but in the opposite direction. Shorting is (in a sense) evening out the odds by inflating the buying pressure at lower stock prices when the borrowers decide to cover and take profits. Bottom line is that, aside from (illegal) insider trading, it doesn't do businesses any good to try to manipulate their stock price or any trading activity. Yes, a company can raise capital by selling additional common shares, but a split really has no effect on the amount of capital they'd be able to raise because it doesn't change the actual market cap, and a dilution is a dilution regardless of the current stock price. If a company's market cap is $1 billion then it doesn't matter if they issue 1 million shares at $50.00 each or 10 million shares at $5.00 each; either way it nets them $50 million from the sale and causes a 5% dilution, to which the market will react accordingly. They don't do it because there'd be no point.\"", "title": "" }, { "docid": "448952", "text": "I don't think that the trading volume would impact a broker's ability to find shares to short. You might think that a lot more people are trying to short a stock during regular trading hours than in the pre-market, and that's probably true. But what's also true is that a lot more people are covering their shorts during regular trading hours than in the pre-market. For stocks that have difficulty in finding shares to short, any time someone covers a short is an opportunity for you to enter a short. If you want to short a stock and your broker is rejecting your order because they can't find shares to short, then I would recommend that you continue placing that order throughout the day. You might get lucky and submit one of those orders right after someone else has covered their short and before anyone else can enter a short. I have had success doing this in the past.", "title": "" }, { "docid": "330041", "text": "\"First, you are not exactly \"\"giving\"\" the brokerage $2000. That money is the margin requirement to protect them in the case the stock price rises. If you short 200 shares as in your example and they are holding $6000 from you then they are protected in the event of the stock price increasing to $30/share. Sometime before it gets there the brokerage will require you to deposit more money or they will cover your position by repurchasing the shares for your account. The way you make money on the short sale is if the stock price declines. It is a buy low sell high idea but in reverse. If you believe that prices are going to drop then you could sell now when it is high and buy back later when it is lower. In your example, you are selling 200 shares at $20 and later, buying those at $19. Thus, your profit is $200, not counting any interest or fees you have paid. It's a bit confusing because you are selling something you'll buy in the future. Selling short is usually considered quite risky as your gain is limited to the amount that you sold at initially (if I sell at $20/share the most I can make is if the stock declines to $0). Your potential to lose is unlimited in theory. There is no limit to how high the stock could go in theory so I could end up buying it back at an infinitely high price. Neither of these extremes are likely but they do show the limits of your potential gain and loss. I used $20/share for simplicity assuming you are shorting with a market order vs a limit order. If you are shorting it would be better for you to sell at 20 instead of 19 anyway. If someone says I would like to give you $20 for that item you are selling you aren't likely to tell them \"\"no, I'd really only like $19 for it\"\"\"", "title": "" }, { "docid": "44635", "text": "Everything on Earth can go wrong. Including, god forbids, your MIL being hit by a bus the next day and your ex inheriting all of her belongings and none of her promises to you. This is a bad idea. What I would suggest doing would be for your MIL to buy your ex a cheap and simple clunker to move herself around without you being ever involved. If you still want to go into this adventure, I'd advise to do these things: A written contract with MIL that details all the terms and agreements. Cover the potential unfortunate events like the one I made up in the first sentence. A written contract with your ex about how and when she can use your car. Insurance to cover all the potential damages and liabilities she can cause, in your name, with her as additional insured. Be ready to bear all the costs associated with the car. You're not a co-signer in this scenario - you're the only signer. The dealership will come after you and you alone.", "title": "" }, { "docid": "265314", "text": "It is not so useful because you are applying it to large capital. Think about Theory of Investment Value. It says that you must find undervalued stocks with whatever ratios and metrics. Now think about the reality of a company. For example, if you are waiting KO (The Coca-Cola Company) to be undervalued for buying it, it might be a bad idea because KO is already an international well known company and KO sells its product almost everywhere...so there are not too many opportunities for growth. Even if KO ratios and metrics says it's a good time to buy because it's undervalued, people might not invest on it because KO doesn't have the same potential to grow as 10 years ago. The best chance to grow is demographics. You are better off either buying ETFs monthly for many years (10 minimum) OR find small-cap and mid-cap companies that have the potential to grow plus their ratios indicate they might be undervalued. If you want your investment to work remember this: stock price growth is nothing more than You might ask yourself. What is your investment profile? Agressive? Speculative? Income? Dividends? Capital preservation? If you want something not too risky: ETFs. And not waste too much time. If you want to get more returns, you have to take more risks: find small-cap and mid-companies that are worth. I hope I helped you!", "title": "" }, { "docid": "317399", "text": "The major drawback to borrowing to invest (i.e. using leverage) is that your return on investment must be high enough to overcome the cost of finance. The average return on the S&P 500 is about 9.8% (from CNBC) a typical unsecured personal loan will have an interest rate of around 18-36% APR (from NerdWallet). This means that on average you will be paying more interest than you are receiving in returns so are losing money on the margin investment. Sometimes the S&P falls and over those periods you would be paying out interest having lost money so will have a negative return! You may have better credit and so be able to get a lower rate but I don't know your loan terms currently. Secured loans, such as remortgaging your house, will have lower costs but come with more life changing risks. The above assumes that you are getting financing by directly borrowing money, however, it is also possible to trade on margin. This is where you post a proportion of the value that you wish to trade with as collateral against a loan to buy the security. This form of finance is normally used by day traders and other short term holders of stocks. Although the financing costs here are low (I am not charged an interest rate on intraday margin trading) there are very high costs if you exceed the term of the loan. An example is that I am charged a fee if I hold a position overnight and my profits and losses are crystallised at that time. If I am in a losing position at that time the crystallisation process and fee can result in not having enough margin to recover the position and the loss of a potentially profit making position. Additionally if the amount of collateral cash (margin) posted is insufficient to cover the expected losses as calculated by your broker they will initiate a margin call asking for more collateral money. If you do not (or cannot) post this extra margin your losing position will be cashed out and you will take as a loss the total loss at that time. Since the market can change very rapidly, such as in a flash crash, this can result in your losing more money than you had in the first place. As this is essentially a loan you can be bankrupted by this. Overall using leverage to invest magnifies your potential profits but it also magnifies your potential losses. In many cases this magnification could be sufficient to lose you more money than you had originally invested. In addition to magnification you need to consider the cost of finance and that your return over the course of the loan needs to be higher than your cost of finance as well as inflation and other opportunity costs of capital. The S&P 500 is a relatively low volatility market in general so is unlikely to return losses in any given period that will mean that leverage of 1.25 times will take you into losses beyond your own capital investment but it is not impossible. The low level of risk automatically means that your returns are lower and so your cost of capital is likely to be a large proportion of your returns and your returns may not completely cover the cost of capital even when you are making money. The key thing if you are going to trade or invest on leverage is to understand the terms and costs of your leverage and discount them from any returns that you receive before declaring to yourself that you are profitable. It is even more important than usual to know how your positions are doing and whether you are covering your cost of capital when using leverage. It is also very important to know the terms of your leverage in detail, especially what will happen when and if your credit runs out for whatever reason be it the end of the financing period (the length of the loan) or your leverage ratio gets too high. You should also be aware of the costs of closing out the loan early should you need to do so and how to factor that into your investing decisions.", "title": "" } ]
1519	Double-Taxation of Royalties paid for in Korea to a US Company	[ { "docid": "310190", "text": "If treaties are involved for something other than exempting student wages on campus, you shouldn't do it yourself but talk to a licensed US tax adviser (EA/CPA licensed in your state) who's well-versed in the specific treaty. Double taxation provisions generally mean that you can credit the foreign tax paid to your US tax liability, but in the US you can do that regardless of treaties (some countries don't allow that). Also, if you're a US tax resident (or even worse - a US citizen), the royalties related treaty provision might not even apply to you at all (see the savings clause). FICA taxes are generally not part of the income tax treaties but totalization agreements (social security-related taxes, not income taxes). Most countries who have income tax treaties with the US - don't have social security totalization agreements. Bottom line - talk to a licensed professional.", "title": "" } ]	[ { "docid": "156743", "text": ">I agree that double taxation makes no sense regardless of individual or corporation. Having said that, it's my understanding that Murca offers corporations tax credits on foreign taxes paid to avoid double taxation. I'm pretty sure that a similar vehicle exists for individuals as well. My issue is entirely with corporations paying off legislators to avoid taxes that they have an obligation to pay in the country that they operate. Context, friend. The statement you quoted was in reference to the issue of double taxation. Hence the statement was made in attempt to indicate that no issue with the responder's stance on double taxation, but in fact the paying for and receiving tax concessions. The statement certainly could have been more comprehensive in identifying legislators as equally culpable in its part. Your attempt to cherry pick a statement out of context is disingenuous. Bro, do you work for Fox?", "title": "" }, { "docid": "552138", "text": "\"The country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The US withholding tax rate on dividends is 30%, although this can be reduced to 15% if there as a tax treaty in place between the US and your country of residence. Malaysia does have a double taxation agreement with the US (see here: http://www.mida.gov.my/env3/index.php?page=double-taxation-agreement) but it is flagged as a \"\"limited\"\" agreement. You'd need to find the full text of the agreement to see whether a reduced rate of dividend withholding tax would be available in the Malaysia/US treaty. See my other answer for more details on withholding taxes and how to partially reclaim under a double tax treaty: What is the dividend tax rate for UK stock Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).\"", "title": "" }, { "docid": "59697", "text": "Equity can be diluted by future investors, royalties get paid on each sale, companies can continue selling things even when operating at negative profit, back royalties due can be negotiated and at least partially paid in a bankruptcy. From the standpoint of the investor: If it doesn't look like the company will likely have commercial success with a second product, it may be wise to simply take a portion of the product that is actually selling rather than risk your capital on the company's future successes (or failures). From the standpoint of the business owner/entreprenuer, if you believe you have a second product close to the end of the development pipeline it would be wise not to give up equity in the entire enterprise simply to gain required financing to ramp up production and marketing on an existing product. Paying a royalty may be advantageous compared to paying interest on a loan as well (royalty payments are contingent on the occurrence of a sale while interest is due regardless).", "title": "" }, { "docid": "586326", "text": "I agree that double taxation makes no sense regardless of individual or corporation. Having said that, it's my understanding that Murca offers corporations tax credits on foreign taxes paid to avoid double taxation. I'm pretty sure that a similar vehicle exists for individuals as well. My issue is entirely with corporations paying off legislators to avoid taxes that they have an obligation to pay in the country that they operate.", "title": "" }, { "docid": "541682", "text": "If you are paid by foreigners then it is quite possible they don't file anything with the IRS. All of this income you are required to report as business income on schedule C. There are opportunities on schedule C to deduct expenses like your health insurance, travel, telephone calls, capital expenses like a new computer, etc... You will be charged both the employees and employers share of social security/medicare, around ~17% or so, and that will be added onto your 1040. You may still need a local business license to do the work locally, and may require a home business permit in some cities. In some places, cities subscribe to data services based on your IRS tax return.... and will find out a year or two later that someone is running an unlicensed business. This could result in a fine, or perhaps just a nice letter from the city attorneys office that it would be a good time to get the right licenses. Generally, tax treaties exist to avoid or limit double taxation. For instance, if you travel to Norway to give a report and are paid during this time, the treaty would explain whether that is taxable in Norway. You can usually get a credit for taxes paid to foreign countries against your US taxes, which helps avoid paying double taxes in the USA. If you were to go live in Norway for more than a year, the first $80,000/year or so is completely wiped off your US income. This does NOT apply if you live in the USA and are paid from Norway. If you have a bank account overseas with more than $10,000 of value in it at any time during the year, you owe the US Government a FinCEN Form 114 (FBAR). This is pretty important, there are some large fines for not doing it. It could occur if you needed an account to get paid in Norway and then send the money here... If the Norwegian company wires the money to you from their account or sends a check in US$, and you don't have a foreign bank account, then this would not apply.", "title": "" }, { "docid": "263361", "text": "Each way you go is a little bit of a gamble. Owning equity in the company is best in situations where you can trade and sell that equity, or where the dilution of your royalty product would affect your returns, or if you can maintain a certain equity stake without working at the company or if you can hold out on taking equity to reinvest profits for the purposes of growth. The royalty is best in situations where you're getting a portion of the gross, since you get paid as a creditor, no matter how the company is performing, or if you intend to collect royalties after you leave the company. Now for your situation: if your royalties are fluctuating with profit instead of gross and your equity is tied to your continued partnership and not subject to potential growth... then they're pretty much both workarounds for the same thing, you've removed the particular advantages for each way of receiving payment. If the company ever does buy out or go public, how much of your additional X earning a month would you have to then re-invest to get an equity stake? And for royalties, if another developer came aboard, or your company bought another company, how much would this dilute your IP contribution? So, aside from the gambling nature of the issue, I'm not sure your tax calculation is right. You can take equity profit as dividend, as long as you're collecting a sufficient salary (this prevents a business from declaring all profits as a dividend). This would put those profits into a different tax bracket, 15% capital gains. Or if all profits are equitably split, you could take part as salary, part as dividend. As well, as someone who's making active income off of their IP, not passive income, you're supposed to file a Schedule C, not a Schedule E, so your royalties would include your self employment taxes. The schedule E is for royalties where the author isn't actively in the field or actually self employed in that area, or if you own royalties on something you didn't create. Should you keep the royalties then go to another job field or retire then your royalties could go on a Schedule E. Now, a tax advantage may exist on a Schedule C if you can write off certain health and business expenses reducing your income that you can't on a Schedule E, though it'd probably be difficult to write off more than the adjusted self employment cost savings of a Schedule E.", "title": "" }, { "docid": "420846", "text": "\"Your wages are an expense to your employer and are therefore 100% tax deductible in the business income. The company should not be paying tax on that, so your double-tax scenario, as described, isn't really correct. [The phrase \"\"double taxation\"\" with respect to US corporations usually comes into play with dividends. In that case, however, it's the shareholders (owners) that pay double. The answer to \"\"why?\"\" in that case can only be \"\"because it's the law.\"\"]\"", "title": "" }, { "docid": "197501", "text": "There is no such thing as double taxation. If you pay tax in the US, you CAN claim tax credits from India tax authority. For example, if you pay 100 tax in USA and your tax liability in India is 200, then you will only pay 100 (200 India tax liability minus 100 tax credits on foreign tax paid in the USA). This is always true and not depending on any treaty. If there is a treaty, the tax rate in the United States is set on the treaty and you CAN claim that final tax rate based upon that treaty. If you operate an LLC, and the income is NOT derived from United States and you have no ties with the US and that LLC is register to a foreign person (not company but a real human) then you will not have to submit tax return in the US... I advice you to read this: http://www.irs.gov/businesses/small/article/0,,id=98277,00.html", "title": "" }, { "docid": "502283", "text": "\"They are basically asking for the name of the legal entity that they should write on the check. You, as a person, are a legal entity, and so you can have them pay you directly, by name. This is in effect a \"\"sole proprietorship\"\" arrangement and it is the situation of most independent contractors; you're working for yourself, and you get all the money, but you also have all the responsibility. You can also set up a legal alias, or a \"\"Doing Business As\"\" (DBA) name. The only thing that changes versus using your own name is... well... that you aren't using your own name, to be honest. You pay some trivial fee for the paperwork to the county clerk or other office of record, and you're now not only John Doe, you're \"\"Zolani Enterprises\"\", and your business checks can be written out to that name and the bank (who will want a copy of the DBA paperwork to file when you set the name up as a payable entity on the account) will cash them for you. An LLC, since it was mentioned, is a \"\"Limited Liability Company\"\". It is a legal entity, incorporeal, that is your \"\"avatar\"\" in the business world. It, not you, is the entity that primarily faces anyone else in that world. You become, for legal purposes, an agent of that company, authorized to make decisions on its behalf. You can do all the same things, make all the same money, but if things go pear-shaped, the company is the one liable, not you. Sounds great, right? Well, there's a downside, and that's taxes and the increased complexity thereof. Depending on the exact structure of the company, the IRS will treat the LLC either as a corporation, a partnership, or as a \"\"disregarded entity\"\". Most one-man LLCs are typically \"\"disregarded\"\", meaning that for tax purposes, all the money the company makes is treated as if it were made by you as a sole proprietor, as in the above cases (and with the associated increased FICA and lack of tax deductions that an \"\"employee\"\" would get). Nothing can be \"\"retained\"\" by the company, because as far as the IRS is concerned it doesn't exist, so whether the money from the profits of the company actually made it into your personal checking account or not, it has to be reported by you on the Schedule C. You can elect, if you wish, to have the LLC treated as a corporation; this allows the corporation to retain earnings (and thus to \"\"own\"\" liquid assets like cash, as opposed to only fixed assets like land, cars etc). It also allows you to be an \"\"employee\"\" of your own company, and pay yourself a true \"\"salary\"\", with all the applicable tax rules including pre-tax healthcare, employer-paid FICA, etc. However, the downside here is that some money is subject to double taxation; any monies \"\"retained\"\" by the company, or paid out to members as \"\"dividends\"\", is \"\"profit\"\" of the company for which the company is taxed at the corporate rate. Then, the money from that dividend you receive from the company is taxed again at the capital gains rate on your own 1040 return. This also means that you have to file taxes twice; once for the corporation, once for you as the individual. You can't, of course, have it both ways with an LLC; you can't pay yourself a true \"\"salary\"\" and get the associated tax breaks, then receive leftover profits as a \"\"distribution\"\" and avoid double taxation. It takes multiple \"\"members\"\" (owners) to have the LLC treated like a partnership, and there are specific types of LLCs set up to handle investments, where some of what I've said above doesn't apply. I won't get into that because the question inferred a single-owner situation, but the tax rules in these additional situations are again different.\"", "title": "" }, { "docid": "196321", "text": "\"What theyre fishing for is whether the money was earned in the U.S. It's essentially an interest shelter, and/or avoiding double taxation. They're saying if you keep income you make outside the US in a bank inside the US, the US thanks you for storing your foreign money here and doesn't tax the interest (but the nation where you earned that income might). There is no question that the AirBNB income is \"\"connected with a US trade or business\"\". So your next question is whether the fraction of interest earned from that income can be broken out, or whether IRS requires you to declare all the interest from that account. Honestly given the amount of tax at stake, it may not be worth your time researching. Now since you seem to be a resident nonresident alien, it seems apparent that whatever economic value you are creating to earn your salary, is being performed in the United States. If this is for an American company and wages paid in USD, no question, that's a US trade or business. But what if it's for a Swedish company running on Swedish servers, serving Swedes and paid in Kroner to a Swedish bank which you then transfer to your US bank? Does it matter if your boots are on sovereign US soil? This is a complex question, and some countries (UK) say \"\"if your boots are in our nation, it is trade/income in our nation\"\"... Others (CA) do not. This is probably a separate question to search or ask. To be clear, the fact that your days as a teacher or trainee do not count toward residency, is a separate question from whether your salary as same counts as US income.\"", "title": "" }, { "docid": "258658", "text": "There is a process called a backdoor IRA. You now have effectively made a Roth IRA contribution in a year where technically you aren't eligible. You do not have to pay taxes on earnings with a Roth IRA. You are limited to the normal annual contribution to the IRA (Roth or traditional). If you don't convert your traditional IRA contribution to a Roth IRA, then you are right. That gains nothing except enhanced protection in bankruptcy. Only do this if you are taking advantage of the Roth rollover. I'm ignoring rolling over a 401k into an IRA, as that doesn't increase the amount you can contribute. This does. You can contribute the full $18,000 to the 401k and still make a full contribution to the backdoor IRA. This is the tax advantaged form of an IRA. This avoids double taxation. Let's assume that your investment can go into something with a 5% annual return and you pay a 25% tax rate (doesn't matter as it drops out). You are going to invest for thirty years and then withdraw. You initially have $1000 before taxes. With a regular investment: You now have $2867.74. With a pre-tax IRA. You now have $3241.45 (it is not an accident that this is almost the same as the amount before the capital gains tax in the example without an IRA). You avoided the $373.72 capital gains tax. Even though you paid a lot more tax, you paid it out of the gains from investing the original $250 that you would have paid in tax. This helps you even more if the capital gains tax goes up in the future. Or if your tax bracket changes. If you currently are in the 25% bracket but retire in the 15% bracket, these numbers will get even better in your favor. If you currently are in the 15% bracket and worry that you might retire in the 25% bracket, consider a Roth instead. It also avoids double taxation but its single taxation is at your current rate rather than your future rate.", "title": "" }, { "docid": "40322", "text": "As an American living in Canada, you don't get it. The USA wants all of us expats to pay taxes twice. No other country but one does that. If the USA would follow the rest of the world and not tax profits again after being taxed abroad, these companies wouldn't leave. We could be having a better conversation here, but it's meaningless buzzwords of patriotism and boycotting. Burger King will have growth and profit internationally. It makes more sense for them to focus on that. If they end up with 20% of their profit from the USA, why would they pay 120% taxes? Obviously it's not quite as simple as that, but you get the general idea. The last thing our politicians want is us talking about eliminating double taxation. Just as you can't be tried for the same crime twice, you should not be taxed twice. When BK pays local taxes in whatever country they're in, whether it's lower or higher than the US is irrelevant. Taxes have been paid. End of story. Doesn't matter if it's a lower rate or creative accounting. It's done.", "title": "" }, { "docid": "185384", "text": "Technically, if you earn in US (being paid there, which means you have a work visa) and live in other country, you must pay taxes in both countries. International treaties try to decrease the double-taxation, and in this case, you may pay in your country the difference of what you have paid in US. ie. your Country is 20% and USA is 15%, you will pay 5%, and vice-versa. This works only with certain areas. You must know the tax legislation of both countries, and I recommend you seek for advisory. This site have all the basic information you need: http://www.irs.gov/Individuals/International-Taxpayers/Foreign-Earned-Income-Exclusion Good luck.", "title": "" }, { "docid": "348799", "text": "No he's arguing for a lower US Corporate tax rate specifically on overseas earnings. Because companies are earning overseas and not taking it back to the US because of our double taxation. He absolutely does not want higher taxes", "title": "" }, { "docid": "4331", "text": "Typically tax treaties will cover double taxation (taxes paid in one jurisdiction are deducted in the other jurisdiction so there is no double tax). You'll need an accountant and attorney with experience in international business setups to confirm and determine which jurisdiction gets first priority of tax payment. In short, this is the wrong place to get a good answer. Talk to (and pay for) professionals to get you properly set up.", "title": "" }, { "docid": "303041", "text": "\"Not specifically a \"\"stream\"\", but there are royalty companies that operate based on a similar concept. With a royalty, a party will pay upfront to a another party, usually a product manufacturer, oil & gas producer, or miner, and in return they will receive a percentage of the proceeds from the sale of the goods. For example, Company A owns 100 sections of land which carry mineral rights and they would like to drill on the land to produce oil & gas. However, Company A does not have the capital to produce the resource. Company B, a royalty company, agrees to provide upfront capital to Company A in return for a royalty, sometimes fixed, sometimes sliding scale based on other factors. The royalty is calculated based on a percentage of the sales proceeds that Company A receives from the sale of their oil & gas production. In this way, royalty companies act similarly to streaming companies, where they provide upfront capital and in return receive a cash flow stream that is dependant on another party's actions. What is different is that the selling price is not fixed. Instead, it is the % of proceeds that is fixed, at least in the short term. In Canada, PrairieSky Royalty and Freehold Royalties do exactly this.\"", "title": "" }, { "docid": "408571", "text": "In 1997, the late David Bowie famously worked with a financier to innovate on a bond issue to be paid back by the royalties on his back catalog, Bowie Bonds Several contemporary musicians followed suit, but Madonna was not one of them. At some point this may change and Madonna or the label that owns part of the catalog may issue bonds backed by royalties. Madonna's catalog pre-2007 is owned by Warner Music which in 2011 was sold by Time-Warner to a private equity company Access Industries. Madonna's post 2007 music including the latest 2015 release is in partnership with LiveNation, a publicly traded company LYV.", "title": "" }, { "docid": "472681", "text": "India and the United States have a tax treaty agreement whereby double taxation is avoided. However check with your accountant in the US who should be able to guide you further in this regard. It is now easier to transfer money out of India. As long as the source of the money is legal and can be verified. So if you decide to sell a property, get payments by way of documented bank transactions like cheques and avoid cash deals. Once taxes are paid money can usually be transferred out.", "title": "" }, { "docid": "123170", "text": "Revenue does not equal income. Income is, more or less, synonymous with profit. It is the amount of money earned after expenses. A corporation is taxed on its revenue after its deductible expenses have been removed, the same as a person is. It's kind of double taxation, but it's kind of the same argument as saying that payroll taxes in addition to income taxes are double taxation. Also of note: taxes on dividends are lower than normal taxes because of this double taxation.", "title": "" }, { "docid": "324921", "text": "Tax Deducted at source is applicable to Employee / Employer [contract employee] relations ... it was also made applicable for cases where an Indian company pays for software products [like MS Word etc] as the product is not sold, but is licensed and is treated as Royalty [unlike sale of a consumer product, that you have, say car] ... Hence it depends on how your contract is worded with your India clients, best is have it as a service agreement. Although services are also taxed, however your contract should clearly specify that any tax in India would be borne by your Indian Client ... Cross Country taxation is an advanced area, you will not find good advice free :)", "title": "" }, { "docid": "52622", "text": "\"I also don't know the specific details for Finland and/or Belgium, however many countries have tax treaties, which generally prevent double taxation (i.e., paying tax in both countries on the same base income). Being that both Finland and Belgium are EU member states, I'm quite certain there's a provision that covers this, and the same would apply: You pay taxes on what you earn while in Finland to Finland, and to Belgium what you earn while in Belgium. All of this is similar to what you presented, however there's also a section where you'd declare how much taxes were paid in other countries. One other thing to note, which will be the determining factor in the above, is whether EU law requires you to change residence to BE for the time you're there. If not then you'll be paying taxes in Finland the entire time on the entire amount. This comes from an Irish governmental site: \"\"By working in another member state and by transferring your residence there, you are likely to become \"\"resident for tax purposes\"\" there. The definition of fiscal residence varies from one member state to another. You must comply with the laws of the country where you have established your residence. The laws on personal taxation vary considerably from one member state to another and you may be liable for taxation in more than one country. In general, you are subject to income tax in the country where you are living but this may not be the case if you are a “posted worker” – see below. In general, property is taxed in the country in which it is situated but, again, there are variations. Tax agreements have been concluded between most of the member states of the EU, which are intended to avoid double taxation, if you derive income from different countries. In general, national fiscal rules must respect the fundamental principle of non-discrimination against nationals of another EU country.\"\"\"", "title": "" }, { "docid": "73457", "text": "\"For non Australian residents: Dividends withholding tax rate is 30%. Depending upon your country of residence where there is a tax treaty in place to avoid double taxation, then this can be reduced. Note that only dividends that are unfranked are subject to this (in Australia, if tax has already been paid by the company then they can distribute dividends as \"\"franked\"\" dividends\"\"). For example, if you owned shares in Commonwealth Bank of Australia (CBA), their most recent dividend from Feb 2015 (Paid 2 April 2015) was $1.98 fully franked. No withholding tax is applicable. There is no capital gains tax for non-residents on share transactions. There are other \"\"tax events\"\" that related to large shareholdings in a company (>10%) with property holdings but I'm guessing that is not an issue. https://www.ato.gov.au/Individuals/Tax-return/2014/In-detail/Publications/You-and-your-shares-2013-14/?page=14 https://www.ato.gov.au/Business/International-tax-for-business/Previous-years/Capital-gains-and-foreign-residents/ https://www.ato.gov.au/Business/International-tax-for-business/Previous-years/Capital-gains-and-foreign-residents/?page=13#Foreign_residents_holding_interests_in_Australian_fixed_trusts https://www.kpmg.com/Global/en/services/Tax/regional-tax-centers/asia-pacific-tax-centre/Documents/CountryProfiles/Australia.pdf\"", "title": "" }, { "docid": "283459", "text": "\"Please declare everything you earn in India as well as the total amount of assets (it's called FBAR). The penalties for not declaring is jail time no matter how small the amount (and lots of ordinary people every 2-3 years are regularly sent to jail for not declaring such income). It's taken very seriously by the IRS - and any Indian bank who has an office in the US or does business here, can be asked by IRS to provide any bank account details for you. You will get deductions for taxes already paid to a foreign country due to double taxation, so there won't be any additional taxes because income taxes in US are on par or even lower than that in India. Using tricks (like transferring ownership to your brother) may not be worth it. Note: you pay taxes only when you realize gains anyway - both in India or here, so why do you want to take such hassles. If you transfer to your brother, it will be taxed only until you hold them. Make sure you have exact dates of gains between the date you came to US and the date you \"\"gifted\"\" to your brother. As long as you clearly document that the stocks transferred to your brother was a gift and you have no more claims on them, it should be ok, but best to consult a CPA in the US. If you have claims on them, example agreement that you will repurchase them, then you will still continue to pay taxes. If you sell your real estate investments in India, you have to pay tax on the gains in the US (and you need proof of the original buying cost and your sale). If you have paid taxes on the real estate gains in India, then you can get deduction due to double tax avoidance treaty. No issues in bringing over the capital from India to US.\"", "title": "" }, { "docid": "523431", "text": "\"If you're a US citizen, money earned while in the US is sourced to the US. So you can't apply FTC/FEIE to the amounts attributable to the periods of your work while in the US even if it is a short business trip. Tax treaties may affect this. Most tax treaties have explicit provisions to exclude short trips from the sourcing rules, however due to the \"\"saving clause\"\" these would probably not apply to you if you're a US citizen - you'll need to read the relevant treaty. Your home country should allow credit for the US taxes paid on the US-sourced income, and the double-taxation avoidance provision should apply in this case. The technicalities depend on your specific country. You would probably not just remove it from the taxable income, there probably is a form similar to the US form 1116 to calculate the available credit.\"", "title": "" }, { "docid": "309684", "text": "See if there are any favorable tax treaties between your two countries. (check US state department - or find the nearest PWC, Deloitte, KPMG, these are global auditing firms that deal with international tax and compliance) A tax treaty could have possible goodies such as a lower more favorable tax or even a tax credit from. For instance, if you paid 28% tax in the US then your new country will give you a credit on the taxes owed to them. The point of tax treaties are to prevent double taxation, but in the effort to do so they often create their own new tax rates for transfers between countries. You'll be better off just paying the 28% US income tax on your 401k distribution. And using the post-tax money as you please. US citizens are on the hook for income tax several years after they leave the US.", "title": "" }, { "docid": "326559", "text": "The link provided by DumbCoder (below) is only relevant to UK resident investors and does not apply if you live in Malaysia. I noticed that in a much older question you asked a similar question about taxes on US stocks, so I'll try and answer both situations here. The answer is almost the same for any country you decide to invest in. As a foreign investor, the country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The rate of DWT that will be withheld is unique to each country. The UK does not have any withholding tax so you will always receive the full dividend on UK stocks. The withholding tax rate for the US is 30%. Other countries vary. For most countries that do charge a withholding tax, it is possible to have this reduced to 15% if there is a double taxation treaty in place between the two countries and all of the following are true: Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).", "title": "" }, { "docid": "401255", "text": "\"Actually 19th century shipped you to us to pretend teaching how \"\"progress\"\" is made, when you only seek to send us backwards. The childish thing said : >It'a a totally different situation. [And you (as I think you don't live in North Korea) still have the choice to leave and reseign if you want btw] Yes, fina lly some sense. Taxation isn't an act of buying its a totally different situation. Taxation was extortion when it was used by despots for \"\"protection\"\", when in fact it was just financing a private interest. But taxation through parliamantary voted law isn't, its the community democratically represented that decide on the rule of majority that there is a need for public services or redistribution to happen in the community. And to do so they decide while granted power by the people to implement taxation. That said, the US govt is frankly corrupted and the US system quite unperforming, but they still somehow protect your rights. The dudes in Irak or Afghanistan are a problem, but the militray is much more than that, protection from invasion is the main utility and your world status as THE power proove you achieve that. This allow you to have access to whole range of products and ressources cheaply and in abundance (agriculture in SA and Africa, Oil etc...), thats for the military. All the thing that make your country a \"\"great\"\" one are funded by your taxes, from your education to your financial sector. You fund your world status and your society status among nation with your taxes. You don't want that ? As I said, you are still free to leave your country and reseign your citizenship. Why ? Because as I see it the majority of your population aren't agaisnt paying taxes, or else they would continuously elect dickwads republicans. \"\"Nah its mah country, gna gna gna\"\" not its not, your country was built by a community,a society that decide though your state/s certain things have to be set up like taxes. You don't want to comply ? Fine, overthrow them or find a \"\"country\"\" free zone. {GOOD LUCK}.\"", "title": "" }, { "docid": "189142", "text": "\"Dividend yields can also reflect important information about the company's status. For example, a company that has never lowered or stopped paying dividends is a \"\"strong\"\" company because it has the cash/earnings power to maintain its dividend regardless of the market. Ideally, a company should pay dividends for at least 10 years for an investor to consider the company as a \"\"consistent payer.\"\" Furthermore, when a company pays dividend, it generally means that it has more cash than it can profitably reinvest in the business, so companies that pay dividends tend to be older but more stable. An important exception is REIT's and their ilk - to avoid taxation, these types of funds must distribute 90% of their earnings to their shareholders, so they pay very high dividends. Just look at stocks like NLY or CMO to get an idea. The issue here, however, is two fold: So a high dividend can be great [if it has been paid consistently] or risky [if the company is new or has a short payment history], and dividends can also tell us about what the company's status is. Lastly, taxation on dividend income is higher than taxation on capital gains, but by reinvesting dividends you can avoid this tax and lower your potential capital gain amount, thus limiting taxes. http://www.tweedy.com/resources/library_docs/papers/highdiv_research.pdf is an excellent paper on dividend yields and investing.\"", "title": "" }, { "docid": "509346", "text": "What do you think of the argument that corporations shouldn't pay any tax, since investors pay tax on the dividends, and if the corporations paid too, that would be double taxation? Of course, not all corporate income goes to pay dividends. Much of the rest is deducted as business expense. Is there some corporate income which should properly be taxed?", "title": "" }, { "docid": "4992", "text": "Yes, this extra income would be taxed at your marginal rate because it is increasing your total income. This does not necessarily apply to all income, however. Capital gains are taxed at a different rate. Depending on the amount of extra work, you may wish to consider setting up a corporation. Corporations are taxed entirely differently. This would also give you the opportunity to write off far more of your expenses, but be aware of double taxation. Investopedia has a good article on double taxation. The issue is that the corporation must pay taxes on the revenue and then, when you take out the money either as salary or dividends, you personally will pay tax. It may leave you better off, even with the double taxation. Dividends are taxed at a lower rate than your marginal tax rate, generally. And you can write off much more inside a corporation. If considering this, talk to an accountant and discuss your expected revenue from consulting. The accountant should be able to quantify the costs and benefits.", "title": "" } ]
PLAIN-2256	toxoplasma	[ { "docid": "MED-4358", "text": "Summary Since their discovery almost a century ago, bacterial viruses (bacteriophages or ‘phages’) have been used to prevent and treat a multitude of bacterial infections (phage therapy: PT). In addition, they have been the basis for many advances in genetics and biochemistry. Phage therapy was performed on human subjects in the United States, Europe and Asia in the few decades following their discovery. However, Western countries largely abandoned PT in favour of antibiotics in the 1940s. The relatively recent renaissance of PT in the West can be attributed partly to the increasing prevalence of antibiotic resistance in human and animal pathogens. However, the stringent controls on human trials now required in the United States and Europe have led to a greater number of domestic animal and agricultural applications as an alternative to PT in man. This trend is set to continue, at least in the short term, with recent approval from the Food and Drug Administration allowing commercial phage treatments to be used in human food in the USA. Nevertheless, despite these significant milestones and the growing number of successful PT trials, significant obstacles remain to their widespread use in animals, food and ultimately medicine in many parts of the world. This review will provide a brief overview of the history of PT in the West and will summarize some of the key findings of phage biocontrol studies in animals and meat products.", "title": "Bacteriophage biocontrol in animals and meat products" }, { "docid": "MED-4131", "text": "In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.", "title": "Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens." }, { "docid": "MED-4142", "text": "Swine confinement buildings in eastern Canada are enclosed and equipped with modern production systems to manage waste. Bioaerosols of these swine confinement buildings could be contaminated by human pathogens and antimicrobial resistant bacteria which could colonize exposed workers. We therefore wanted to analyze bioaerosols of swine confinement buildings and nasal flora of Canadian hog producers to evaluate possible colonization with human pathogens and tetracycline-resistant bacteria. Culturable and non-culturable human pathogens and tet genes were investigated in the bioaerosols of 18 barns. The nasal passages of 35 hog producers were sampled and total DNA was extracted from the calcium-alginate swabs to detect, by PCR, Campylobacter, C. perfringens, Enterococcus, E. coli, Y. enterocolitica, tetA/tetC, tetG and ribosomal protection protein genes. Airborne culturable C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were present in the bioaerosols of 16, 17, 11 and 6 of the 18 facilities. Aerosolized total (culturable/non culturable) Campylobacter, C. perfringens, Enterococcus, E. coli and Y. enterocolitica were detected in 10, 6, 15, 18 and 2 barns, respectively. Tet genes were found in isolates of culturable human pathogens. TetA/tetC, tetG and ribosomal protection protein genes were detected in the bioaerosols of all 18 studied buildings. Campylobacter, C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were found respectively in 4, 9, 17, 14 and one nasal flora of workers. One and 10 workers were positive for tetA/tetC and tetG genes, respectively. In swine confinement buildings, hog producers are exposed to aerosolized human pathogens and tetracycline-resistant bacteria that can contaminate the nasal flora. Copyright © 2010 Elsevier GmbH. All rights reserved.", "title": "Human pathogens and tetracycline-resistant bacteria in bioaerosols of swine confinement buildings and in nasal flora of hog producers." }, { "docid": "MED-4128", "text": "Various methods have been described in the literature for the detection of virulent Yersinia enterocolitica in pigs. The risk factors for pig herd contamination have yet to be determined. The objective of this study was to validate a sensitive method for the detection of Y. enterocolitica and to describe the distribution of the bacteria in pigs at slaughter from conventional and alternative (\"organic\") housing systems. First, samples were collected from tonsils, caecum with caecal contents, and the caecal lymph nodes of 60 slaughter pigs. These samples were used to compare the sensitivity of six different laboratory culture methods either in common use or described in the literature with that of a polymerase chain reaction with two primer pairs (multiplex PCR). Then, only PCR was used to examine tonsils, caecum and caecal lymph nodes from two groups of slaughter pigs: 210 from six conventional fattening farms and 200 from three with alternative housing. The results of the multiplex PCR were positive in 28 cases. All culture methods proved inferior to PCR in sensitivity. In the second part of the study, PCR detected 36 (18%) positive pigs from alternative housing and 60 (29%) from conventional housing (p<0.05). The highest rate of Y. enterocolitica contamination was found in tonsils (11% alternative, 22% conventional; p<0.05), followed by caecum (5%, 11%) and lymph nodes (2%, 7%). The housing system appears to be one important factor in the prevalence of this common pathogen in pig herds, as we found important differences between the two systems studied here. In the conventional system, the main risk factors appeared to be sourcing pigs from different pig suppliers, use of commercial feed and transportation to slaughter.", "title": "Validation of a method for the detection of virulent Yersinia enterocolitica and their distribution in slaughter pigs from conventional and alterna..." }, { "docid": "MED-4137", "text": "Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.", "title": "Prevalence of Yersinia enterocolitica in different phases of production on swine farms." }, { "docid": "MED-4140", "text": "A survey of 788 pigs from 120 farms was conducted to determine the within-farm prevalence of pathogenic Yersinia enterocolitica and a questionnaire of management conditions was mailed to the farms afterwards. A univariate statistical analysis with carriage and shedding as outcomes was conducted with random-effects logistic regression with farm as a clustering factor. Variables with a P value <0·15 were included into the respective multivariate random-effects logistic regression model. The use of municipal water was discovered to be a protective factor against carriage and faecal shedding of the pathogen. Organic production and buying feed from a certain feed manufacturer were also protective against total carriage. Tonsillar carriage, a different feed manufacturer, fasting pigs before transport to the slaughterhouse, higher-level farm health classification, and snout contacts between pigs were risk factors for faecal shedding. We concluded that differences in management can explain different prevalences of Y. enterocolitica between farms.", "title": "Factors related to the prevalence of pathogenic Yersinia enterocolitica on pig farms." }, { "docid": "MED-4136", "text": "BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.", "title": "Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10..." }, { "docid": "MED-4135", "text": "Yersinia enterocolitica are ubiquitous, being isolated frequently from soil, water, animals, and a variety of foods. They comprise a biochemically heterogeneous group that can survive and grow at refrigeration temperatures. The ability to propagate at refrigeration temperatures is of considerable significance in food hygiene. Virulent strains of Yersinia invade mammalian cells such as HeLa cells in tissue culture. Two chromosomal genes, inv and ail, were identified for cell invasion of mammalian. The pathogen can cause diarrhoea, appendicitis and post-infection arthritis may occur in a small proportion of cases. The most common transmission route of pathogenic Y. enterocolitica is thought to be fecal-oral via contaminated food. Direct person-to-person contact is rare. Occasionally, pathogenic Y. enterocolitica has been detected in vegetables and environmental water; thus, vegetables and untreated water are also potential sources of human yersiniosis. However, the isolation rates of pathogenic Y. enterocolitica have been low, which may be due to the limited sensitivity of the detection methods. To identify other possible transmission vehicles, different food items should be studied more extensively. Many factors related to the epidemiology of Y. enterocolitica, such as sources, transmission routes, and predominating genotypes remain obscure because of the low sensitivity of detection methods.", "title": "Behavior of Yersinia enterocolitica in Foods" }, { "docid": "MED-734", "text": "A total of 28 domestic ducks were divided into seven groups of four ducks. Six groups were inoculated per os with 10(1), 10(2), 10(3), 10(4), 10(5) and 10(5.7) oocysts Toxoplasma gondii oocysts (K21 strain, which is avirulent for mice), and the remaining group was used as a control. Antibodies to T. gondii were detected in all ducks by the indirect fluorescence antibody test first on day 7 post-inoculation (p.i.). Antibody titres were found in the range of 1:20 to 1:640 depending on the infectious dose of the oocysts. From day 14 p.i. antibody titres increased to 1:80 to 1:20 480. Between days 14 and 28 p.i. (end of the experiment), antibody titres decreased in 14 ducks, remained the same in seven ducks, and continued to increase in three ducks. Bioassay in mice revealed T. gondii in the breast and leg muscles and the heart (100%, n=47), brain (91%, n=22), liver (54%, n=13) and stomach (46%, n=24). The infected ducks showed no clinical signs; however, the results of bioassay indicate that, compared with some gallinaceous birds, domestic ducks were relatively susceptible to T. gondii infection.", "title": "Susceptibility of the domestic duck (Anas platyrhynchos) to experimental infection with Toxoplasma gondii oocysts." }, { "docid": "MED-733", "text": "The present paper presents an overview of current knowledge of amyloid arthropathy in chickens, and covers the pathogenesis of amyloidosis in general and in birds, field cases reported, and the studies performed to assess the amyloidogenicity of various agents compared to that of Enterococcus faecalis. An animal model of amyloid arthropathy is presented, as are studies on the pathogenesis of arthropathic and amyloidogenic E. faecalis infections in brown layers. The review concludes with a description of the pathology of amyloid arthropathy, the biochemical characterization of the chicken joint amyloid protein as being of the AA type, investigation of the serum amyloid A (SAA) gene involved, and local SAA mRNA expression in joint and liver.", "title": "Amyloid arthropathy in chickens." }, { "docid": "MED-4129", "text": "Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.", "title": "Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms." }, { "docid": "MED-4133", "text": "BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.", "title": "Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study." }, { "docid": "MED-4139", "text": "Pigs are the major animal reservoir for Yersinia enterocolitica strains, which are potentially pathogenic for humans. The goals of this study were (i) to estimate the individual animal and on-farm prevalences of Y. enterocolitica in hogs based on tonsil samples collected during National Animal Health Monitoring System Swine 2002 study and (ii) to use these data with data previously published for fecal samples to determine on-farm risk factors for Y. enterocolitica. Tonsil swabs (1,218) and fecal samples (2,847) were collected on 124 farms located in the top 17 pork-producing states. Ten percent of tonsils (122 of 1,218 samples) were positive in irgasan-tiracillin-chlorate (ITC) enrichment broth by real-time PCR, but only 5.6% of samples (68 of 1,218) were positive after subculture on the more selective cefsulodin-irgasan-novobiocin (CIN) agar. For tonsils, the on-farm prevalence based on real-time PCR detection of the ail gene in ITC enrichment broth cultures was 32% (32 of 100 premises sampled); the prevalence based on subculture in CIN agar was 19.6% (20 of 102 premises). Results of bacteriological isolation and real-time PCR analysis of tonsils and feces were combined to estimate prevalence (individual animal and farm), which was subsequently correlated with 40 farm management practices. Four factors and their accompanying odds ratios (ORs) were identified in the final regression model: location in a central state (OR = 0.3), vaccination for Escherichia coli (OR = 3.0), percentage of deaths due to scours (OR = 3.5), and presence of meat or bone meal in grower-finisher diet (OR = 4.1).", "title": "Prevalence of Yersinia enterocolitica in market weight hogs in the United States." }, { "docid": "MED-4143", "text": "In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.", "title": "Yersinia enterocolitica infection in diarrheal patients." }, { "docid": "MED-4134", "text": "Yersinia enterocolitica is considered an important food-borne pathogen impacting the pork production and processing industry in the United States. Since this bacterium is a commensal of swine, the primary goal of this study was to determine the prevalence of pathogenic Y. enterocolitica in pigs in the United Sates using feces as the sample source. A total of 2,793 fecal samples were tested for its presence in swine. Fecal samples were collected from late finisher pigs from 77 production sites in the 15 eastern and midwestern pork-producing states over a period of 27 weeks (6 September 2000 to 20 March 2001). The prevalence of ail-positive Y. enterocolitica was determined in samples using both a fluorogenic 5′ nuclease PCR assay and a culture method. The mean prevalence was 13.10% (366 of 2,793 fecal samples tested) when both PCR- and culture-positive results were combined. Forty-one of 77 premises (53.25%) contained at least one fecal sample positive for the ail sequence. The PCR assay indicated a contamination rate of 12.35% (345/2,793) compared to 4.08% (114/2,793) by the culture method. Of the 345 PCR-positive samples, 252 were culture negative, while of the 114 culture-positive samples, 21 were PCR negative. Among 77 premises, the PCR assay revealed a significantly (P < 0.05) higher percentage (46.75%, n = 36 sites) of samples positive for the pathogen (ail sequence) than the culture method (22.08%, n = 17 sites). Thus, higher sensitivity, with respect to number of samples and sites identified as positive for the PCR method compared with the culture method for detecting pathogenic Y. enterocolitica, was demonstrated in this study. The results support the hypothesis that swine are a reservoir for Y. enterocolitica strains potentially pathogenic for humans.", "title": "Prevalence of Pathogenic Yersinia enterocolitica Strains in Pigs in the United States" }, { "docid": "MED-4956", "text": "Little information is available on the presence of viable Toxoplasma gondii in tissues of lambs worldwide. The prevalence of T. gondii was determined in 383 lambs (<1 year old) from Maryland, Virginia and West Virginia, USA. Hearts of 383 lambs were obtained from a slaughter house on the day of killing. Blood removed from each heart was tested for antibodies to T. gondii by using the modified agglutination test (MAT). Sera were first screened using 1:25, 1:50, 1: 100 and 1:200 dilutions, and hearts were selected for bioassay for T. gondii. Antibodies (MAT, 1:25 or higher) to T. gondii were found in 104 (27.1%) of 383 lambs. Hearts of 68 seropositive lambs were used for isolation of viable T. gondii by bioassay in cats, mice or both. For bioassays in cats, the entire myocardium or 500g was chopped and fed to cats, one cat per heart and faeces of the recipient cats were examined for shedding of T. gondii oocysts. For bioassays in mice, 50g of the myocardium was digested in an acid pepsin solution and the digest inoculated into mice; the recipient mice were examined for T. gondii infection. In total, 53 isolates of T. gondii were obtained from 68 seropositive lambs. Genotyping of the 53 T. gondii isolates using 10 PCR-restriction fragment length polymorphism markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) revealed 57 strains with 15 genotypes. Four lambs had infections with two T. gondii genotypes. Twenty-six (45.6%) strains belong to the clonal Type II lineage (these strains can be further divided into two groups based on alleles at locus Apico). Eight (15.7%) strains belong to the Type III lineage. The remaining 22 strains were divided into 11 atypical genotypes. These results indicate high parasite prevalence and high genetic diversity of T. gondii in lambs, which has important implications in public health. We believe this is the first in-depth genetic analysis of T. gondii isolates from sheep in the USA.", "title": "High prevalence and abundant atypical genotypes of Toxoplasma gondii isolated from lambs destined for human consumption in the USA." }, { "docid": "MED-4141", "text": "To study the origin and spread of Yersinia enterocolitica among pigs, fecal and blood samples were repeatedly taken on a fattening farm. A few piglets were found to be already infected on breeding farms. After the piglets were mixed, the infection spread through the whole unit. Eventually, all the pigs excreted the pathogen.", "title": "Piglets Are a Source of Pathogenic Yersinia enterocolitica on Fattening-Pig Farms" }, { "docid": "MED-4132", "text": "Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.", "title": "Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic..." }, { "docid": "MED-4955", "text": "Research on infectious agents as a possible cause of schizophrenia has become prominent in the past decade. Toxoplasma gondii has emerged as a prime candidate for a variety of reasons; (i) many studies have reported that individuals with schizophrenia, compared to controls, have a higher prevalence of antibodies to T. gondii, (ii) some individuals with adult toxoplasmosis develop psychotic symptoms similar to those of schizophrenia, (iii) epidemiologically, there are many similarities between toxoplasmosis and schizophrenia, (iv) antipsychotic drugs known to be effective in schizophrenia also inhibit some parasites, including T. gondii, (v) Toxoplasma has been shown to induce elevated levels of dopamine in experimentally infected animals (elevated dopamine is commonly seen in individuals with schizophrenia) and (vi) studies have shown that individuals with schizophrenia, compared to controls, have had greater exposure to cats in childhood. A number of questions remain concerning a role for Toxoplasma in the aetiology of schizophrenia, including the roles of strain variation, the timing and source of infection, and the role of host genes in determining disease susceptibility. The establishment of a firm association between Toxoplasma and the aetiology of schizophrenia and related disorders would represent a major breakthrough in the understanding of these disorders and would lead to novel methods for their treatment and prevention.", "title": "Toxoplasma and schizophrenia." }, { "docid": "MED-4138", "text": "Yersinia enterocolitica is a zoonotic agent that causes gastrointestinal disease in humans, as well as reactive arthritis and erythema nodosum. Enteropathogenic Yersinia are the etiological agents for yersiniosis, which can be acquired through the consumption of contaminated foods. As porcine animals are the main carriers of Y. enterocolitica, food safety measures to minimize human infection are of increasing interest to the scientific and medical community. In this review, we examine why it is imperative that information on the reservoirs, prevalence, virulence, and ability of this pathogen to survive in different environments is further investigated to provide rational measures to prevent or decrease associated disease risks.", "title": "Yersinia enterocolitica: a brief review of the issues relating to the zoonotic pathogen, public health challenges, and the pork production chain." }, { "docid": "MED-4130", "text": "We investigated characteristics of Yersinia enterocolitica infection in Ontario finisher pig herds. Our specific objectives were to estimate or test: prevalence of Y. enterocolitica shedding in finisher pigs, bioserotype distribution, agreement between the herd-level tests based on sampling pig and pooled fecal samples, whether bioserotypes cluster by farms, and whether Y. enterocolitica-positive herds cluster spatially. In total, 3747 fecal samples were collected from 100 farms over the years 2001, 2002, and 2004 (250 total herd visits). Fecal samples were tested by culture and positive isolates were biotyped and serotyped. Apparent pig-level prevalence of Y. enterocolitica was 1.8%, 3.2%, and 12.5% in 2001, 2002, and 2004, respectively. Estimated true pig-level prevalence of Y. enterocolitica was 5.1%, 9.1%, and 35.1% in 2001, 2002, and 2004, respectively. Herd-level prevalence was 16.3%, 17.9%, and 37.5% in 2001, 2002, and 2004, respectively. In all years, the most common bioserotype was 4, O:3, followed by bioserotype 2, O:5,27. Kappa between herd-level status based on pig and pooled samples ranged between 0.51 and 0.68 for biotype 1A and bioserotype 4, O:3, respectively. For 4, O:3, a significant bias in discordant pairs was detected, indicating that pig samples were more sensitive than pooled samples in declaring a herd as positive. Farms tended to be repeatedly positive with the same bioserotype, but positive study farms did not cluster spatially (suggesting lack of between herd transmission and lack of a common geographic risk factor). Copyright 2009 Elsevier B.V. All rights reserved.", "title": "Prevalence of Yersinia enterocolitica shedding and bioserotype distribution in Ontario finisher pig herds in 2001, 2002, and 2004." } ]	[ { "docid": "MED-4763", "text": "The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.", "title": "An obesity-associated gut microbiome with increased capacity for energy harvest." }, { "docid": "MED-3446", "text": "Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.", "title": "Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women." }, { "docid": "MED-845", "text": "Histone deacetylases (HDAC) control gene expression by changing histonic as well as non histonic protein conformation. HDAC inhibitors (HDACi) are considered to be among the most promising drugs for epigenetic treatment for cancer. Recently a strict relationship between histone hyperacetylation in specific tissues of mouse embryos exposed to two HDACi (valproic acid and trichostatin A) and specific axial skeleton malformations has been demonstrated. The aim of this study is to verify if boric acid (BA), that induces in rodents malformations similar to those valproic acid and trichostatin A-related, acts through similar mechanisms: HDAC inhibition and histone hyperacetylation. Pregnant mice were treated intraperitoneally with a teratogenic dose of BA (1000 mg/kg, day 8 of gestation). Western blot analysis and immunostaining were performed with anti hyperacetylated histone 4 (H4) antibody on embryos explanted 1, 3 or 4 h after treatment and revealed H4 hyperacetylation at the level of somites. HDAC enzyme assay was performed on embryonic nuclear extracts. A significant HDAC inhibition activity (compatible with a mixed type partial inhibition mechanism) was evident with BA. Kinetic analyses indicate that BA modifies substrate affinity by a factor alpha=0.51 and maximum velocity by a factor beta=0.70. This work provides the first evidence for HDAC inhibition by BA and suggests such a molecular mechanism for the induction of BA-related malformations.", "title": "Boric acid inhibits embryonic histone deacetylases: a suggested mechanism to explain boric acid-related teratogenicity." }, { "docid": "MED-1827", "text": "BACKGROUND: Actin cytoskeleton is involved in actin-based cell adhesion, cell motility, and matrix metalloproteinases(MMPs) MMP2, MMP9, MMP11 and MMP14 are responsible for cell invasion in breast cancer metastasis. The dietary intake of lignan from flax seed gets converted to enterolactone (EL) and enterodiol in the human system. Here we show that the enterolactone has a very significant anti-metastatic activity as demonstrated by its ability to inhibit adhesion and invasion and migration in MCF-7 and MDA MB231 cell lines. MATERIALS AND METHODS: Migration inhibition assay, actin-based cell motility assay along with reverse transcriptase polymerase chain reaction (RT-PCR) for MMP2, MMP9, MMP11 and MMP14 genes were performed in MCF-7 and MDA MB 231 cell lines. RESULTS: Enterolactone seems to inhibit actin-based cell motility as evidenced by confocal imaging and photo documentation of cell migration assay. The results are supported by the observation that the enterolactone in vitro significantly down-regulates the metastasis-related metalloproteinases MMP2, MMP9 and MMP14 gene expressions. No significant alteration in the MMP11 gene expression was found. CONCLUSIONS: Therefore we suggest that the anti-metastatic activity of EL is attributed to its ability to inhibit cell adhesion, cell invasion and cell motility. EL affects normal filopodia and lamellipodia structures, polymerization of actin filaments at their leading edges and thereby inhibits actin-based cell adhesion and cell motility. The process involves multiple force-generating mechanisms of actin filaments i.e. protrusion, traction, deadhesion and tail-retraction. By down-regulating the metastasis-related MMP2, MMP9 and MMP14 gene expressions, EL may be responsible for cell invasion step of metastasis.", "title": "In vitro anti-metastatic activity of enterolactone, a mammalian lignan derived from flax lignan, and down-regulation of matrix metalloproteinases i..." }, { "docid": "MED-1179", "text": "The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term \"organic,\" reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.", "title": "Organic foods: health and environmental advantages and disadvantages." }, { "docid": "MED-3893", "text": "Seven cyclists exercised at 70% of maximal O2 uptake (VO2max) until fatigue (170 +/- 9 min) on three occasions, 1 wk apart. During these trials, plasma glucose declined from 5.0 +/- 0.1 to 3.1 +/- 0.1 mM (P less than 0.001) and respiratory exchange ratio (R) fell from 0.87 +/- 0.01 to 0.81 +/- 0.01 (P less than 0.001). After resting 20 min the subjects attempted to continue exercise either 1) after ingesting a placebo, 2) after ingesting glucose polymers (3 g/kg), or 3) when glucose was infused intravenously (\"euglycemic clamp\"). Placebo ingestion did not restore euglycemia or R. Plasma glucose increased (P less than 0.001) initially to approximately 5 mM and R rose (P less than 0.001) to approximately 0.83 with glucose infusion or carbohydrate ingestion. Plasma glucose and R then fell gradually to 3.9 +/- 0.3 mM and 0.81 +/- 0.01, respectively, after carbohydrate ingestion but were maintained at 5.1 +/- 0.1 mM and 0.83 +/- 0.01, respectively, by glucose infusion. Time to fatigue during this second exercise bout was significantly longer during the carbohydrate ingestion (26 +/- 4 min; P less than 0.05) or glucose infusion (43 +/- 5 min; P less than 0.01) trials compared with the placebo trial (10 +/- 1 min). Plasma insulin (approximately 10 microU/ml) and vastus lateralis muscle glycogen (approximately 40 mmol glucosyl U/kg) did not change during glucose infusion, with three-fourths of total carbohydrate oxidation during the second exercise bout accounted for by the euglycemic glucose infusion rate (1.13 +/- 0.08 g/min).(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Reversal of fatigue during prolonged exercise by carbohydrate infusion or ingestion." }, { "docid": "MED-1802", "text": "Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.", "title": "Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed." }, { "docid": "MED-3544", "text": "Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in monoamine oxidase (MAO) activity, which reverts to control level when they quit smoking. The observed decrease in MAO activity in smokers is presumably due to their exposure to tobacco constituents that possess MAO-inhibiting properties. The inhibition of MAO activity seems, however, not to be a unique feature of tobacco smoking as subjects with Type II alcoholism have been reported to show a similar decrease in MAO activity that reverses when they cease to use alcohol. The present review summarizes the data on MAO-inhibiting tobacco constituents and explains that the decrease in MAO activity observed in alcoholics is probably due to concomitant tobacco use. It is concluded that the inhibition of MAO by constituents contained in tobacco and tobacco smoke, enhances the addiction induced by tobacco smoking.", "title": "Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction." }, { "docid": "MED-5173", "text": "Rhabdomyolysis is a potentially life-threatening disorder that occurs as a primary disease or as a complication of a broad spectrum of other diseases. We report the first case of acute rhabdomyolysis after ingestion of Spirulina (Arthrospira platensis), a plantonic blue-green alga, as a dietary supplement.", "title": "Acute rhabdomyolysis caused by Spirulina (Arthrospira platensis)." }, { "docid": "MED-2599", "text": "Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.", "title": "Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre..." }, { "docid": "MED-2257", "text": "Background Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III). Methods NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), the Serial Digit Learning Test (SDLT) trials-to-criterion, and the SDLT total-error-score (SDLT-tests: learning recall/short-term memory). We fit multivariable-adjusted models to estimate associations between urinary cadmium concentrations and test scores. Results 5662 participants underwent neurocognitive screening, and 5572 (98%) of these had a urinary cadmium level available. Prior to multivariable-adjustment, higher urinary cadmium concentration was associated with worse performance in each of the 4 outcomes. After multivariable-adjustment most of these relationships were not significant, and age was the most influential variable in reducing the association magnitudes. However among never-smokers with no known occupational cadmium exposure the relationship between urinary cadmium and SDST score (attention/perception) was significant: a 1 μg/L increase in urinary cadmium corresponded to a 1.93% (95%CI: 0.05, 3.81) decrement in performance. Conclusions These results suggest that higher cumulative cadmium exposure in adults may be related to subtly decreased performance in tasks requiring attention and perception, particularly among those adults whose cadmium exposure is primarily though diet (no smoking or work based cadmium exposure). This association was observed among exposure levels that have been considered to be without adverse effects and these levels are common in U.S. adults. Thus further research into the potential neurocognitive effects of cadmium exposure is warranted. Because cumulative cadmium exposure may mediate some of the effects of age and smoking on cognition, adjusting for these variables may result in the underestimation of associations with cumulative cadmium exposure. Prospective studies that include never-smokers and non-occupationally exposed individuals are needed to clarify these issues.", "title": "Associations between cadmium exposure and neurocognitive test scores in a cross-sectional study of US adults" }, { "docid": "MED-4364", "text": "Tracing risk factors for acquiring hepatitis C virus (HCV) in an HCV-infected patient, the only identified risk was working at the same butcher's counter of a supermarket as another HCV-infected patient, using a common ham cutting machine, with frequent bleeding hand injuries. A phylogenetic analysis showed a high percentage of nucleotide homology between the two patients' strains. © 2010 European Society of Clinical Microbiology and Infectious Diseases. No claim to original US government works.", "title": "Occupational transmission of hepatitis C virus resulting from use of the same supermarket meat slicer." }, { "docid": "MED-5016", "text": "OBJECTIVE: The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. DESIGN: The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. SUBJECTS: Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. INTERVENTIONS: Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. RESULTS: Plasma lathosterol concentration (P < 0.001), the ratio plasma lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (P<0.001) and apoB (P<0.001) levels were significantly different among the diets and were significantly lower during coconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (P< or =0.001) different among the diets and were not significantly different between buffer and coconut diets. CONCLUSIONS: These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.", "title": "Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels." }, { "docid": "MED-1069", "text": "AIMS/HYPOTHESIS: Prolonged elevation of plasma specific fatty acids may exert differential effects on glucose-stimulated insulin secretion (GSIS), insulin sensitivity and clearance. SUBJECTS AND METHODS: We examined the effect of oral ingestion, at regular intervals for 24 h, of an emulsion containing either predominantly monounsaturated (MUFA), polyunsaturated (PUFA) or saturated (SFA) fat or water (control) on GSIS, insulin sensitivity and insulin clearance in seven overweight or obese, non-diabetic humans. Four studies were conducted in each individual in random order, 4-6 weeks apart. Twenty-four hours after initiation of oral ingestion, subjects underwent a 2 h, 20 mmol/l hyperglycaemic clamp to assess GSIS, insulin sensitivity and insulin clearance. RESULTS: Following oral ingestion of any of the three fat emulsions over 24 h, plasma NEFAs were elevated by approximately 1.5- to 2-fold over the basal level. Ingestion of any of the three fat emulsions resulted in reduction in insulin clearance, and SFA ingestion reduced insulin sensitivity. PUFA ingestion was associated with an absolute reduction in GSIS, whereas insulin secretion failed to compensate for insulin resistance in subjects who ingested SFA. CONCLUSIONS/INTERPRETATION: Oral ingestion of fats with differing degrees of saturation resulted in different effects on insulin secretion and action. PUFA ingestion resulted in an absolute reduction in insulin secretion and SFA ingestion induced insulin resistance. Failure of insulin secretion to compensate for insulin resistance implies impaired beta cell function in the SFA study.", "title": "Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clear..." }, { "docid": "MED-706", "text": "Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity. Copyright 2009 Elsevier GmbH. All rights reserved.", "title": "The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans." }, { "docid": "MED-2587", "text": "Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a \"high-protein\" (high protein group/HPG) diet, which they believed would \"improve\" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p<0.001) significant. Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.", "title": "The effect of high-protein diets on coronary blood flow." }, { "docid": "MED-4550", "text": "BACKGROUND/OBJECTIVES: Vegetarian diet has become an increasing trend in western world and in Poland. The frequency of allergies is growing, and the effectiveness of vegetarian diet in allergic diseases is a concern for research. We aimed to study an effect of vegetarian diet on lipid profile in serum in a group of Polish children in Poland and to investigate lipid parameters in healthy vegetarian children and in omnivorous children with diagnosed atopic disease. SUBJECTS/METHODS: Serum lipid profiles (triglycerides, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, fatty acids) were assessed in groups of children: healthy vegetarians (n=24) and children with diagnosed atopic diseases (n=16), with control group of healthy omnivores (n=18). Diet classification was assessed by a questionnaire. RESULTS: No differences were observed in serum triglycerides, LDL cholesterol and saturated and monounsaturated fatty acids level in all groups. In the group of Polish vegetarian children, we recorded high consumption of vegetable oils rich in monounsaturated fatty acid, and sunflower oil containing linoleic acid. This observation was associated with higher content of linoleic acid in serum in this group. Among polyunsaturated n-6 fatty acids, linoleic acid revealed significantly (P<0.05) lower levels in allergy vs vegetarian groups. In case of eicosapentaenoic acid (n-3 fatty acid), the allergy group showed higher levels of this compound in comparison to vegetarians. CONCLUSIONS: Significantly higher concentration of linoleic acid in vegetarian children in comparison to allergy group indicated possible alternative path of lipid metabolism in studied groups, and in consequence, some elements of vegetarian diet may promote protection against allergy.", "title": "An impact of the diet on serum fatty acid and lipid profiles in Polish vegetarian children and children with allergy." }, { "docid": "MED-5101", "text": "When making food choices, consumers are faced with the dilemma of reconciling differences between health benefits and exposure to potential toxins. Analyses to estimate likely intake and exposure outcomes for young children and women of child-bearing age shows that seafood, chicken, and beef, while approximately equivalent in protein, vary in key nutrients of importance as well as in levels of certain contaminants. Increasing the variety of choices among meats, poultry, and seafood and consuming them in amounts consistent with current dietary guidelines and advisories will contribute toward meeting nutritional needs while reducing exposure to any single type of contaminant.", "title": "Nutrient and contaminant tradeoffs: exchanging meat, poultry, or seafood for dietary protein." }, { "docid": "MED-5322", "text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.", "title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting." }, { "docid": "MED-3536", "text": "Epidemiologists have published more than 50 studies of insomnia based on data collected in various representative community-dwelling samples or populations. These surveys provide estimates of the prevalence of insomnia according to four definitions: insomnia symptoms, insomnia symptoms with daytime consequences, sleep dissatisfaction and insomnia diagnoses. The first definition, based on insomnia criteria as defined by the DSM-IV, recognizes that about one-third of a general population presents at least one of them. The second definition shows that, when daytime consequences of insomnia are taken into account, the prevalence is between 9% and 15%. The third definition represents 8-18% of the general population. The last definition, more precise and corresponding to a decision-making diagnosis, sets the prevalence at 6% of insomnia diagnoses according to the DSM-IV classification. These four definitions of insomnia have higher prevalence rates in women than in men. The prevalence of insomnia symptoms generally increases with age, while the rates of sleep dissatisfaction and diagnoses have little variation with age. Numerous factors can initiate or maintain insomnia. Mental disorders and organic diseases are the factors that have been the most frequently studied. The association between insomnia and major depressive episodes has been constantly reported: individuals with insomnia are more likely to have a major depressive illness. Longitudinal studies have shown that the persistence of insomnia is associated with the appearance of a new depressive episode. Future epidemiological studies should focus on the natural evolution of insomnia. Epidemiological genetic links of insomnia are yet to be studied.", "title": "Epidemiology of insomnia: what we know and what we still need to learn." }, { "docid": "MED-5142", "text": "OBJECTIVE: We describe a case of irreversible subacute sclerotic combined degeneration of the spinal cord in a Western vegan subject. METHODS: A 57-y-old man, member of a vegan cult for 13 y, developed weakness, paraplegia, hyper-reflexia, distal symmetric muscular hypotrophy, impairment of superficial sensation in the hands and feet, loss of deep sensation in the lower limbs, and neurogenic bladder and bowel. Magnetic resonance imaging of the cervical and dorsal spine disclosed abnormally increased signal intensity on T(2)-weighted sections in the posterior and lateral columns. Subacute sclerotic combined degeneration of the spinal cord was diagnosed and treatment with cobalamin was started. RESULTS: Despite rehabilitative treatment, the patient developed spastic hypertonia with mild improvement of paresthesias. Six months later, vitamin B12 plasma levels and hematological analysis were normal. One year later, spastic paraplegia was still present and the patient was unable to walk despite improvement on magnetic resonance imaging. CONCLUSION: Irreversible subacute sclerotic combined degeneration of the spinal cord is a rare but possible effect of a strict vegetarian diet.", "title": "Irreversible subacute sclerotic combined degeneration of the spinal cord in a vegan subject." }, { "docid": "MED-2141", "text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population." }, { "docid": "MED-3832", "text": "Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.", "title": "Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know." }, { "docid": "MED-1238", "text": "The relationship between dietary fat and glucose metabolism has been recognized for at least 60 years. In experimental animals, high fat diets result in impaired glucose tolerance. This impairment is associated with decreased basal and insulin-stimulated glucose metabolism. Impaired insulin binding and/or glucose transporters has been related to changes in the fatty acid composition of the membrane induced by dietary fat modification. In humans, high-fat diets, independent of fatty acid profile, have been reported to result in decreased insulin sensitivity. Saturated fat, relative to monounsaturated and polyunsaturated fat, appears to be more deleterious with respect to fat-induced insulin insensitivity. Some of the adverse effects induced by fat feeding can be ameliorated with omega-3 fatty acid. Epidemiological data in humans suggest that subjects with higher intakes of fat are more prone to develop disturbances in glucose metabolism, type 2 diabetes or impaired glucose tolerance, than subjects with lower intakes of fat. Inconsistencies in the data may be attributable to clustering of high intakes of dietary fat (especially animal fat) with obesity and inactivity. Metabolic studies suggest that higher-fat diets containing a higher proportion of unsaturated fat result in better measures of glucose metabolism than high-carbohydrate diet. Clearly, the area of dietary fat and glucose metabolism has yet to be fully elucidated.", "title": "Relationship of dietary fat to glucose metabolism." }, { "docid": "MED-4942", "text": "The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.", "title": "Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey." }, { "docid": "MED-3513", "text": "Background Functional abdominal pain syndrome (FAPS) has chronic unexplained abdominal pain and is similar to the psychiatric diagnosis of somatoform pain disorder. A patient with irritable bowel syndrome (IBS) also has chronic unexplained abdominal pain, and rectal hypersensitivity is observed in a majority of the patients. However, no reports have evaluated the visceral sensory function of FAPS precisely. We aimed to test the hypothesis that FAPS would show altered visceral sensation compared to healthy controls or IBS. The present study determined the rectal perceptual threshold, intensity of sensation using visual analogue scale (VAS), and rectal compliance in response to rectal balloon distention by a barostat in FAPS, IBS, and healthy controls. Methods First, the ramp distention of 40 ml/min was induced and the thresholds of discomfort, pain, and maximum tolerance (mmHg) were measured. Next, three phasic distentions (60-sec duration separated by 30-sec intervals) of 10, 15 and 20 mmHg were randomly loaded. The subjects were asked to mark the VAS in reference to subjective intensity of sensation immediately after each distention. A pressure-volume relationship was determined by plotting corresponding pressures and volumes during ramp distention, and the compliance was calculated over the linear part of the curve by calculating from the slope of the curve using simple regression. Results Rectal thresholds were significantly reduced in IBS but not in FAPS. The VAS ratings of intensity induced by phasic distention (around the discomfort threshold of the controls) were increased in IBS but significantly decreased in FAPS. Rectal compliance was reduced in IBS but not in FAPS. Conclusion An inconsistency of visceral sensitivity between lower and higher pressure distention might be a key feature for understanding the pathogenesis of FAPS.", "title": "Altered rectal sensory response induced by balloon distention in patients with functional abdominal pain syndrome" }, { "docid": "MED-3443", "text": "Incidence of the metabolic syndrome is increasing worldwide, with notable exceptions of some Asian countries where seaweeds are commonly consumed. 13 men (mean age 47.4+/-9.9 yr) and 14 women (average age 45.6+/-12.2 yr) with at least one symptom of the metabolic syndrome were recruited in Quito Ecuador to a randomized double-blinded placebo-controlled trial. Subjects were assigned to either Group 1 (1 m placebo, followed by 1 m 4 g/d seaweed [Undaria pinnatifida]) or Group 2 (1 m of 4 g/d seaweed, followed by 1 m of 6 g/d of seaweed). Blood pressure, weight, waist circumference, inflammation biomarkers, and lipids were measured monthly. Repeated measures analysis of variance with Tukey's multiple comparison tests were used for statistical analysis. In Group 2, systolic blood pressure decreased 10.5 mmHg after a month of 6 g/d seaweed (95% CI: 4.1, 16.8 mmHg; p<0.05), primarily in subjects with high-normal baseline blood pressure. Waist circumference changed only for women participants, with a 2.4 cm decrease in Group 1 after treatment with placebo (95% CI: 1.0, 3.7 cm; p<0.01). In Group 2, women had a mean decrease of 2.1 cm after 4 g/d (95% CI: 0.4, 3.7 cm; p<0.05) and a further 1.8 cm decrease after 1 m 6 g/d seaweed (95 % CI: 0.1, 3.4, p<0.05). No other changes were observed. Consumption of 4 to 6 g/d seaweed, typical for most people in Japan, may be associated with low metabolic syndrome prevalence.", "title": "Could dietary seaweed reverse the metabolic syndrome?" }, { "docid": "MED-4581", "text": "We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.", "title": "Fruit and vegetable consumption and cognitive decline in aging women." }, { "docid": "MED-4004", "text": "Evidence suggests that monounsaturated and polyunsaturated fats facilitate greater absorption of carotenoids than saturated fats. However, the comparison of consuming a polyunsaturated fat source versus a saturated fat source on tomato carotenoid bioaccumulation has not been examined. The goal of this study was to determine the influence of coconut oil and safflower oil on tomato carotenoid tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat diet. Coconut oil feeding increased carotenoid concentrations among many compartments including total carotenoids in the serum (p = 0.0003), adrenal glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all-trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils. Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut oil enhanced tissue uptake of tomato carotenoids to a greater degree than safflower oil. These results may have been due to the large proportion of medium-chain fatty acids in coconut oil, which might have caused a shift in cholesterol flux to favor extrahepatic carotenoid tissue deposition.", "title": "Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower oil in the Mongolian gerbil ( Meriones unguiculatus )." }, { "docid": "MED-3352", "text": "The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional \"primary\" or \"basic\" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®", "title": "Are free fatty acids effective taste stimuli in humans? Presented at the symposium \"The Taste for Fat: New Discoveries on the Role of Fat in Sensor..." } ]
540	Tax planning for Indian TDS on international payments	[ { "docid": "324921", "text": "Tax Deducted at source is applicable to Employee / Employer [contract employee] relations ... it was also made applicable for cases where an Indian company pays for software products [like MS Word etc] as the product is not sold, but is licensed and is treated as Royalty [unlike sale of a consumer product, that you have, say car] ... Hence it depends on how your contract is worded with your India clients, best is have it as a service agreement. Although services are also taxed, however your contract should clearly specify that any tax in India would be borne by your Indian Client ... Cross Country taxation is an advanced area, you will not find good advice free :)", "title": "" }, { "docid": "274188", "text": "I am an Israeli based citizen who represents and Indian company who sells its products in Israel. As an agent I am entitled to commission on sales on behalf the Indian company who advised that. Any commission paid to you will be applicable to TDS at 20.9% of the commission amount, the tax will be paid and a Tax paid certificate will be given to you. According to a Bilateral Double tax avoidance treaty if the tax has been deducted in India you will get credit for this tax in Israel.", "title": "" } ]	[ { "docid": "89662", "text": "I assume that you are a citizen of India, and are what Indian law calls a NRI (NonResident Indian) and thus entitled to operate an NRE (NonResident External) account in India. You can deposit US dollars into the NRE account, but the money is converted to Indian Rupees (INR) and held as INR. You can withdraw the money and bring it back to the US as US dollars, but the INR will be converted to US$ at the exchange rate applicable on the date of the transaction. With the recent decline of the Indian Rupee against the US dollar, many NRE accounts lost a lot of their value. You can deposit any amount of money in your NRE account. Some banks may limit the amount you can send in one business day, but if 250 times that amount seriously limits the amount of money you want to send each year, you should not be asking here; there are enough expensive lawyers, bankers and tax advisors who will gladly guide you to a satisfactory solution. There is no limitation on the total amount that you can have in your NRE account. The earnings (interest paid) on the sum in your NRE account is not taxable income to you in India but you may still need to file an income tax return in India to get a refund of the tax withheld by the bank (TDS) and sent to the tax authorities. The bank should not withhold tax on the earnings in an NRE account but it did happen to me (in the past). While the interest paid on your NRE account is not taxable in India, it is taxable income to you on your US tax returns (both Federal and State) and you must declare it on your tax return(s) even though the bank will not issue a 1099-INT form to you. Be aware also about the reporting requirements for foreign accounts (FBAR, TD F90-22.1 etc). Lots of people ignored this requirement in the past, but are more diligent these days after the IRS got a truckload of information about accounts in foreign banks and went after people charging them big penalties for not filing these forms for ever so many years. There was a huge ruckus in the Indian communities in the US about how the IRS was unfairly targeting simple folks instead of auditing the rich! But, if the total value of the accounts did not exceed $10K at any time of the year, these forms do not need to be filed. It seems, though, that you will not fall under this exemption since you are planning on having considerably larger sums in your NRE account. So be sure and follow the rules.", "title": "" }, { "docid": "260889", "text": "As NRI/PIO (Non-Resident Indian/Person of Indian Origin), the overseas income and transfers in foreign currency are exempt from Indian income taxes. However, the account in India has to be designated NRE or FCNR. There are three kind of accounts that an NRI can maintain Interest earned in NRE and FCNR accounts is exempt from income taxes. Interest earned in NRO accounts is not exempt from income taxes, in fact banks would withhold about 30% of interest (TDS). The exact tax liability would depend upon income generated in India and TDS could be applied towards that liability when the tax returns are filed. There are other implications also of designating the account as NRE or NRO. NRE accounts can only be funded via inward remittance of permitted foreign currency e.g. deposit USD/GBP. So proceeds like rental income, pension etc. that are generated in INR within India can't be deposited in this account. The money deposited in NRE account can grow tax free and can be converted back in any foreign currency freely. On the other hand NRO accounts can be funded through both inward remittance of permitted foreign currency or local income e.g. rental, pension etc. All the amount in this account is treated as Indian originated INR (even if remitted in foreign currency) and thus is taxed as any other bank account. The amount in this account is subject to the annual cap of convertibility of USD 1 million. Both NRE and NRO accounts are maintained in INR and can be Saving and Term Deposit. Any remittance made to these accounts in any foreign currency is converted to INR at the time of deposit and is maintained in INR. FCNR account are held in foreign currency and can only be Term Deposit. Official definitions: Accounts for Non Resident Indians (NRIs) and Persons of Indian Origin (PIOs)", "title": "" }, { "docid": "586772", "text": "Citizens of India who are not residents to India (have NRI status) are not entitled to have ordinary savings accounts in India. If you have such accounts (e.g. left them behind to support your family while you are abroad), they need to be converted to NRO (NonResident Ordinary) accounts as soon as possible. Your bank will have forms for completion of this process. Any interest that these accounts earn will be taxable income to you in India, and possibly in the U.K. too, though tax treaties (or Double Taxation Avoidance Agreements) generally allow you to claim credit for taxes paid to other countries. Now, with regard to your question, NRIs are entitled to make deposits into NRO accounts as well as NRE (NonResident External) accounts. The differences are that money deposited into an NRE account, though converted to Indian Rupees, can be converted back very easily to foreign currency if need be. However, the re-conversion is at the exchange rate then in effect, and you may well lose that 10% interest earned because of a change in exchange rate. Devaluation of the Indian Rupee as occurred several times in the past 70 years. Once upon a time, it was essentially impossible to take money in an NRO account and convert it to foreign currency, but under the new recently introduced schemes, money in an NRO account can also be converted to foreign currencies, but it needs certification by a CA, and various forms to be filled out, and thus is more hassle. interest earned by the money in an NRE account is not taxable income in India, but is taxable income in the U.K. There is no taxable event (neither in U.K. nor in India) when you change an ordinary savings account held in India into an NRO account, or when you deposit money from abroad into an NRE or NRO account in an Indian bank. What is taxable is the interest that you receive from the Indian bank. In the case of an NRO account, what is deposited into your NRO account is the interest earned less the (Indian) income tax (usually 20%) deducted at the source (TDS) and sent to the Income Tax Authority on your behalf. In the case of an NRE account, the full amount of interest earned is deposited into the NRE account -- no TDS whatsoever. It is your responsibility to declare these amounts to the U.K. income tax authority (HM Revenue?) and pay any taxes due. Finally, you say that you recently moved to the U.K. for a job. If this is a temporary job and you might be back in India very soon, all the above might not be applicable to you since you would not be classified as an NRI at all.", "title": "" }, { "docid": "563812", "text": "If you are a citizen of India and working in Germany, then you are most likely an NRI (NonResident Indian). If so, you are not entitled to hold an ordinary Indian bank account, and all such existing accounts must be converted to NRO (NonResident Ordinary) accounts. If your Indian bank knows about NRO accounts, then it will be eager to assist you in the process of converting your existing accounts to NRO accounts most likely it also offers a money remittance scheme (names like Remit2India or Money2India) which will take Euros from your EU bank account and deposit INR into your NRO account. Or, you can create an NRE (NonResident External) account to receive remittances from outside India. The difference is that interest earned in an NRO account is taxable income to you in India (and subject to TDS, tax deduction at source) while interest earned in an NRE account is not taxable in India. The remittance process takes a while to set up, but once in place, most remittances take 5 to 6 business days to complete.", "title": "" }, { "docid": "298587", "text": "My account is with Indian Bank, if that's relevant. Indian Bank already has SWIFT BIC. Is there any way I can receive such international transfers in my account if the bank branch itself is not SWIFT enabled? The Branch need not be SWIFT enabled. However the Bank needs to be SWIFT enabled. Indian Bank is SWIFT enabled and has several Correspondent Banks in US. See this link on Indian Bank Website Select USD as filter in bottom page. It will list quite a few Banks that are correspondent to the Indian Bank. Click on the Link and it will give you more details. For example with Citi Bank as Correspondent. In the Beneficiary account details fill in your account details etc and send this to the company and they should be able to send you a payment based on this.", "title": "" }, { "docid": "68154", "text": "\"You will always pay the 10% penalty and the income tax on the money, so even if you withdraw amounts below the taxable limits - you still pay 10% tax. However, you can probably offset that from your Indian tax liability on the money. If you convert it to Roth - you should check with an Indian tax accountant/adviser what the Indian tax treatment would be. It is likely that \"\"Roth\"\" advantages are unrecognized by foreign countries, so you may end up paying taxes on both the conversion (in the US) and the distribution (in India). Check with a tax adviser who's knowledgeable about the Indo-US tax treaty and the tax laws in both the countries, this may be trickier than people with no international tax experience may think.\"", "title": "" }, { "docid": "512267", "text": "It is best to take advise from / appoint a professional CA. Will I have to pay GST? No GST is applicable. Exports outside of India do not have GST. Do I have to collect TDS when I send money to the PUBLISHERS ? No But another guy said, I have to pay 18% tax when receiving and sending payments, apart from that I have to collect 30.9% TDS when sending payment to the PUBLISHERS(outside India). There is only income tax applicable on profits. So whatever you get from Advertisers less of payments to publishers less of your expenses is your profit. Since you are doing this as individual, you will have to declare this as income from other sources and pay income tax as appropriate. Note there are restrictions on sending payments outside of India plus there are exchange rate fluctuations. It is best you open an Foreign Currency Resident [or Domestic] Account. This will enable you payout someone without much issues. Else you will have to follow FEMA and LRS schemes of RBI.", "title": "" }, { "docid": "111999", "text": "Would I have to pay income tax other then TDS on interest earned on my saving bank account. No being NRI you are not taxed in India on income outside of India. I am sending money from EU to my OWN saving account. Please note this account is not NRI\\NRO\\FCNR As an NRI you CANNOT by law hold a regular Savings Account. Please convert this account to NRO ASAP. Does the channel I use to transfer money to India would make any difference? Its 3rd party transfer service. Whether you transfer the funds or not is irrelevant. As the income was during the period when your status is NRI, there is no Tax in India. sold some shares from my Indian demat account online and got some STCG. You would need to pay tax on this in India Edit: Self Assessment Tax can be paid till 30 July 2015 for the Financial Year 1 April 2014 to 31 March 2015. Tax have to be paid in advance, so if your tax obligation is more than Rs 10,000/- there will be an interest at 1% per month and penalty at 1% per month payable", "title": "" }, { "docid": "187734", "text": "\"The Option 2 in your answer is how most of the money is moved cross border. It is called International Transfer, most of it carried out using the SWIFT network. This is expensive, at a minimum it costs in the range of USD 30 to USD 50. This becomes a expensive mechanism to transfer small sums of money that individuals are typically looking at. Over a period of years, the low value payments by individuals between certain pair of countries is quite high, example US-India, US-China, Middle-East-India, US-Mexico etc ... With the intention to reduce cost, Banks have built a different work-flow, this is the Option 1. This essentially works on getting money from multiple individuals in EUR. The aggregated sum is converted into INR, then transferred to partner Bank in India via Single SWIFT. Alongside the partner bank is also sent a file of instructions having the credit account. The Partner Bank in India will use the local clearing network [these days NEFT] to credit the funds to the Indian account. Option 3: Other methods include you writing a check in EUR and sending it over to a friend/relative in India to deposit this into Indian Account. Typically very nominal costs. Typically one month of timelines. Option 4: Another method would be to visit an Indian Bank and ask them to issue a \"\"Rupee Draft/Bankers Check\"\" payable in India. The charges for this would be higher than Option 3, less than Option 1. Mail this to friend/relative in India to deposit this into Indian Account. Typically couple of days timelines for transfer to happen.\"", "title": "" }, { "docid": "102442", "text": "Some brokerages will allow you to enroll your account in a dividend reinvestment plan -- TD Ameritrade and I think Schwab for example. The way the plan works is that they would take your $4 and give you whatever fractional share of the ETF it is worth on the payment date. There are no fees associated with this purchase (or at least there are in the programs I've seen -- if you have to pay a fee, look for another brokerage). You may also be able to enroll specific securities instead of the entire account into dividend reinvestment. Call your brokerage to see what they offer.", "title": "" }, { "docid": "238503", "text": "No such law in existence or planning. There are no limits on what you can transfer in or out of the USA, as long as you're not doing tax evasion/money laundering, or violating embargo laws against specific countries and organizations. Explanation why Rob's answer is wrong: There's no, and never has been, withholding requirement when transferring money between own accounts. FATCA doesn't impose any new withholding. It reinforces the existing 30% withholding requirement, and suggests that the 30% withholding requirement may supersede treaty positions. Generally internal legislation cannot supersede international treaties, so I'm very skeptical about the US Gov't ability to enforce this. 30% withholding on payments to foreign people/entities has always been there. It's not new. Certain payments that are income sourced in the US and being remitted to foreign payees is subject to 30% withholding (unless treaty says otherwise). There's nothing new about it, been like that forever.", "title": "" }, { "docid": "97490", "text": "The money that you have under your control (e.g. in bank accounts, savings accounts, taxable investments, etc) is your money and there is no tax of any kind (either in India or in US) that needs to be paid when the money is transferred to India. As Dheer's answer says, you need to transfer all these monies within 7 years as per Indian tax law. For your 401(k) account, assuming that all the money is tax-deferred (i.e. you contributed to a regular 401(k) and not a Roth 401(k)), you will have separated from service as far as US tax law is concerned. So, check if it is at all possible to roll over the money into a similar scheme in India, specifically the Employees Provident Fund. Wikipedia says The schemes covers both Indian and international workers (for countries with which bilateral agreements have been signed; 14 such social security agreements are active). and so a rollover might be possible. If not, you could withdraw small amounts each year and avoid US income tax (but not the 10% excise tax), but how long you can continue holding 401(k) assets after return to India and whether that is long enough to drain the 401(k) are things that you need to find out.", "title": "" }, { "docid": "5219", "text": "Most US banks don't allow you the ability to draft a foreign currency check from USD. Though, I know Canadian banks are more workable. For instance, TD allows you to do this from CAD to many other currencies for a small fee. I believe even as a US Citizen you can quite easily open a TD Trust account and you'd be good to go. Also, at one time Zions bank was one of the few which lets US customers do this add-hoc. And there is a fee associated. Even as a business, you can't usually do this without jumping thru hoops and proving your business dealings in foreign countries. Most businesses who do this often will opt to using a payment processor service from a 3rd party which cuts checks in foreign currencies at a monthly and per check base. Your other option, which may be more feasible if you're planning on doing this often, would be to open a British bank account. But this can be difficult if not impossible due to the strict money laundering anti-fraud regulations. Many banks simply won't do it. But, you might try a few of the newer British banks like Tesco, Virgin and Metro.", "title": "" }, { "docid": "20987", "text": "1) The easy way is to find a job and they will assign you an SSN. 2) Here's the hard way. If you're Canadian, open a TD Boarderless account in the U.S. Put a small investment into any investment that would generate some type of income, such as capital gain, dividends, interest and etc... Then you will need to file a US tax return to declare your income if you receive U.S. tax slips (although you're likely below the min filing requirement) at year end. To file a U.S. tax return, you may need what's called an ITIN or individual tax id number. With the ITIN, you can get credit from the US TD boarderless account (only). Consider getting a prepaid US credit card with the TD account to futher build credit at that specific bank. It's not much credit, but you do start with creating a history.", "title": "" }, { "docid": "251370", "text": "If the funds are in NRE account, then there is no issue. You just instruct your bank in India to transfer. If your tax status in India is Non-Resident Indian, you should not be holding a normal Savings bank account. Under the liberalized remittance scheme you can transfer upto 2,50,000 USD per year. You would need to instruct your bank in India to initiate a international wire transfer. The FAQs are here", "title": "" }, { "docid": "72251", "text": "Indian exporters run a chain of dangers when entering into new foreign lands with their new products. Exportation of products helps in growing national economies and expanding the international market. For more information simply visit our website now: https://www.seair.co.in/indian-export-data.aspx", "title": "" }, { "docid": "239780", "text": "\">SS is not an investment. It is a Tax. Learn the difference. Thus you pay for it with the Federal Insurance Contributions Act tax (FICA). It is not an investment, you do not have an account with your money, it has always been a pay as you go plan, just like medicare, funds for schools, and all the other programs. SS is collected like a tax, but if it is infact a tax, why can I opt out of it? Come on, you really aren't trying to win an arguement about SS by saying its a \"\"tax\"\" and not a \"\"investment\"\". That's seriously the weakest bullshit, who the fuck cares the symantics of how its \"\"collected\"\".. The arguement is still the same, with no USA no SS. It is, therefore, a ponzi by definition. >The US government wrote the laws that specify exactly who can opt out. Most people cannot just opt out because they don't meet the criteria. Again you're wrong. Joining and quitting Obtaining a Social Security number for a child is voluntary.[26] Further, there is no general legal requirement that individuals join the Social Security program (although, under normal circumstances, FICA taxes must be collected anyway). Although the Social Security Act itself does not require a person to have a Social Security Number (SSN) to live and work in the United States,[27] the Internal Revenue Code does generally require the use of the social security number by individuals for federal tax purposes: The social security account number issued to an individual for purposes of section 205(c)(2)(A) of the Social Security Act shall, except as shall otherwise be specified under regulations of the Secretary [of the Treasury or his delegate], be used as the identifying number for such individual for purposes of this title.[28] Importantly, most parents apply for Social Security numbers for their dependent children in order to[29] include them on their income tax returns as a dependent. Everyone filing a tax return, as taxpayer or spouse, must have a Social Security Number or Taxpayer Identification Number (TIN) since the IRS is unable to process returns or post payments for anyone without an SSN or TIN. The FICA taxes are imposed on all workers and self-employed persons. Employers are required[30] to report wages for covered employment to Social Security for processing Forms W-2 and W-3. There are some specific wages which are not a part of the Social Security program (discussed below). Internal Revenue Code provisions section 3101[31] imposes payroll taxes on individuals and employer matching taxes. Section 3102[32] mandates that employers deduct these payroll taxes from workers' wages before they are paid. Generally, the payroll tax is imposed on everyone in employment earning \"\"wages\"\" as defined in 3121[33] of the Internal Revenue Code.[34] and also taxes[35] net earnings from self-employment.[36] Seriously, you need to learn how to use google asshole. Stop looking like an idiot and posting blatent lies.\"", "title": "" }, { "docid": "251713", "text": "A company can issue different kinds of shares. For example, some kinds of shares may get preference in dividends or payment in event of (company) bankruptcy. Preferred shares are an example of this. A company might have several kinds of preferred shares and a 'common stock'. Here is a good explanation. See too the Wikipedia article about preferred stock. Toronto-Dominion Bank (TD) is an example of a company that has fourteen different preferred share issues, each with its own listing on the Toronto Stock Exchange (TSE) and symbol. TD has one kind of common stock, which is also listed on the TSE. However, TD common equity trades much more actively than the preferred shares. Remember that preferred stock is a different security type than common stock e.g. common has voting rights, preferred does not.", "title": "" }, { "docid": "107215", "text": "According to this page on their website (http://www.kotaksecurities.com/internationaleq/homepage.htm), Kotak Securities is one big-name Indian broker that offers an international equities account to its Indian customers. Presumably, they should be able to answer all your questions. Since this is a competitive market, one can assume that others like ICICI Direct must also be doing so.", "title": "" }, { "docid": "212770", "text": "Ielts British Council is the best company in the world for IELTS certification. We provide ielts certification service all over the world. We also provide the international work permit. If you want to Indian ielts certificates, then you can visit our company website and Buy indian ielts certificates. We provide the original certificates for those, who for one reason or the other are unable to take the test", "title": "" }, { "docid": "229911", "text": "Please find out whether you are considered to be a tax resident of the US from the date that you received the permanent immigrant visa or from the date that you first enter the US on that visa. If the former, and you received the visa after April 30, you might be a part-year resident of India for Indian Income Tax purposes for the current tax year. You need to convert your bank accounts including Fixed Deposits (the FDs that you mention) to NRO accounts as soon as possible. You will need to keep at least one NRO account open for a year or more to receive the final interest payments on your FDs as well as the proceeds of cashing in the FDs, not to mention any refunds of Indian Income Tax that may be due to you for last year or the current year. Once you are done with all these, follow the procedures outlined in this excellent answer by @Dheer to transfer the money to your US account. At this point, you can close the NRO account if you wish. As PeterK's comment says, it is not a good idea to bring a large sum of cash with you unless you are really really paranoid about banking channels. Note that if you insist on bringing cash (whether it is INR or USD) or negotiable instruments (checks or bank drafts) with you when you land in the US, these will have to be declared on entry if the total exceeds US$ 10K. There is no limit to how much you can bring with you as long as you declare it. Transfers of your own money from India to the US is not taxable income to you in the US, and income tax will already have been paid/withheld on that money in India, and so there is no income tax liability in India either on the sum transferred.", "title": "" }, { "docid": "429747", "text": "For any money you plan on taking back with you to India in a couple of years, you need to consider whether you expect the U.S. dollar to gain strength compared to the Indian rupee, and if so, by enough to make up the difference in interest rates. According to exchange-rates.org, $1 USD would buy you 44.22576 INR on April 29, 2011, and 49.41525 on October 25, 2011. If the Indian rupee keeps on losing strength against the U.S. dollar at that rate, you are far, far better to keep your money in U.S. currency. On the other hand, if the Indian rupee gains strength, you'd be better to convert your money as soon as possible. There are, of course, other options if you plan to keep your money in the U.S., many of which will pay more than 0.01% interest.", "title": "" }, { "docid": "354943", "text": "If the 'gratuity' is a payment from your previous Indian company made when you left them, then the US tax system will treat it exactly the same as wages paid by your previous company. Whether or not you need to pay taxes on your wages and gratuity will depend on whether your are considered resident in the US for tax purposes for this financial year. It is likely that you will be. Assuming you are, then the US requires that you pay tax on all income, wherever it is earned in the world. You will need to fill in a tax return and declare both your gratuity and your wages in India for that year. India and the US have a 'double tax agreement', which means essentially that you won't be taxed twice if you have already paid tax on the gratuity and wages in India. But you do have to declare them.", "title": "" }, { "docid": "511583", "text": "No it is not required to create a trade account or a current account. If the payment is via Paypal, as per Indian laws, it would automatically get credited to your savings account in 7 days. You would still need to declare this as income and pay tax accordingly.", "title": "" }, { "docid": "118383", "text": "It seems that your Organizers are not familiar with dealing transfers outside of Euro Zone. You are right IBAN is not used in India. A Bank in France can initiate an International Wire. There are few Banks that offer this online, for most one has to visit the Branch. See this https://expatriates.stackexchange.com/questions/2862/international-money-transfer-online-from-a-french-bank I am not aware of any other term used in France for International Wire, try explaining; Its also called BIC. It would help if you also provide your Correspondent Bank details [This will be a Bank in Europe]. This should be available on your Indian Bank's website.", "title": "" }, { "docid": "322838", "text": "How much amount can we transfer from India to the USA? Is the limit per year? As I understand your father in law is Indian Citizen and his tax paid earnings need to be transferred outside of India. Under the Liberalized Remittance Scheme by RBI, one can transfer upto 2,50,000 USD. Please check with your Bank for the exact paperwork. A form 15CA and 15CB [by CA] are required to establish taxes have been paid. What documents we have to present to the bank? See above. Should money be transferred to company's account(Indian Company) to USA company? or can be transferred to my husband's account. Transfer of funds by a Indian Company to US Company has some restrictions. Please check with CA for details. If you father in law has sold the Indian Company and paid the taxes in India; he can transfer the proceeds to his son in US as per the Liberalized Remittance Scheme. Can they just gift the whole amount to my husband? What will be the tax implication on my husband's part in USA and on my father in law in India. The whole amount can be gifted by your father in law to your husband [his son]. There is no tax implication in India as being an Indian resident, gift between close relatives is tax free. There is no tax implication to your husband as he is a US Citizen and as per gift tax the person giving the gift should be paying the applicable taxes. Since the person gifting is not US Citizen; this is not applicable.", "title": "" }, { "docid": "575241", "text": "Part 1 Quite a few [or rather most] countries allow USD account. So there is no conversion. Just to illustrare; In India its allowed to have a USD account. The funds can be transfered as USD and withdrawn as USD, the interest is in USD. There no conversion at any point in time. Typically the rates for CD on USD account was Central Bank regulated rate of 5%, recently this was deregulated, and some banks offer around 7% interest. Why is the rate high on USD in India? - There is a trade deficit which means India gets less USD and has to pay More USD to buy stuff [Oil and other essential items]. - The balance is typically borrowed say from IMF or other countries etc. - Allowing Banks to offer high interest rate is one way to attract more USD into the country in short term. [because somepoint in time they may take back the USD out of India] So why isn't everyone jumping and making USD investiments in India? - The Non-Residents who eventually plan to come back have invested in USD in India. - There is a risk of regulation changes, ie if the Central Bank / Country comes up pressure for Forex Reserves, they may make it difficut to take back the USD. IE they may impose charges / taxes or force conversion on such accounts. - The KYC norms make it difficult for Indian Bank to attract US citizens [except Non Resident Indians] - Certain countries would have explicit regulations to prevent Other Nationals from investing in such products as they may lead to volatility [ie all of them suddenly pull out the funds] - There would be no insurance to foreign nationals. Part 2 The FDIC insurance is not the reason for lower rates. Most countires have similar insurance for Bank deposits for account holdes. The reason for lower interst rate is all the Goverments [China etc] park the excess funds in US Treasuries because; 1. It is safe 2. It is required for any international purchase 3. It is very liquid. Now if the US Fed started giving higher interest rates to tresaury bonds say 5%, it essentially paying more to other countries ... so its keeping the interest rates low even at 1% there are enough people [institutions / governemnts] who would keep the money with US Treasury. So the US Treasury has to make some revenue from the funds kept at it ... it lends at lower interest rates to Bank ... who in turn lend it to borrowers [both corporate and retail]. Now if they can borrow cheaply from Fed, why would they pay more to Individual Retail on CD?, they will pay less; because the lending rates are low as well. Part 3 Check out the regulations", "title": "" }, { "docid": "305742", "text": "Wow, very amused by some of the answers. I will comment on those later. To directly answer your question, here is a link to a brochure that explains the three basic typs and is written in straightforward language. link text That is step one. Step 2 is a question, cheapest when, initially or for long term? Without a doubt term initially is the cheapest. However every 10 years or 20 years it increases in price. As the name term implies it is temporary. Coverage will end at some point, 75, or 80 depending upon plan design chosen. It is possible that if you choose Term you can outlive your coverage and all you have are a bunch of cancelled cheques. Young people with a mortgage, children and other debts should buy a lot of term as the mortgage will be paid off, the kids will no longer be dependent. These needs are temporary. However some needs are permanent. What about leaving a Legacy at Death to a Charity? Insurance is a good solution and can provide a tax deduction too. Term isn't a good fit. Or a business owner wishing to transfer his/her business at death to their children. Taxes will be due and permanent insurance such as Whole Life and Universal Life can be arranged to provide cash to pay tax whenever this happens. Let me ask you who received 10% in the last ten years on their equity portfolio. Almost zero people did. However a Whole Plan would have generated a guaranteed return of 3.0% plus a non-guaranteed return via dividends that the combined internal rate of return on a combined basis would be about 5.6% AFTER TAXES. Life a bond portfolio yield. (Internal rate of return is dependent on age at buying, years of investing. All insurance comany software can show you the internal rate of return.) IRR is essesntially: what is the return after tax that you must get to equal the equity or death benefit from a permanent insurance plan. Someone mentioned by Term and Invest the difference. That is what universal life is, Term and Invest the difference except the difference is growing tax sheltered.Outside investments with comparable risk are taxable! There is no easy answer for what type is right, often a combination is. The key question you should ask is How Much Is Enough? Then consider types based upon your needs and budget. Here is a link where you can calculate how much you need. I hope this helps a bit.", "title": "" }, { "docid": "55108", "text": "From what I understand this is what you can do : You need to raise an invoice to your brother's company in USA Your brother makes a payment into your Indian company's bank account using wire transfer straight into a bank account in your company's name. Your brother wont have to pay taxes on the money that he pays you against an invoice as it would be an expense and would not be considered as profit for tax purposes. Once you have the money you can then file your income tax returns after deducting your own expenses etc in India. I hope this helps.", "title": "" }, { "docid": "268294", "text": "\"If they directly paid for your education, it is possible that it wouldn't count as taxable income to you according to the IRS, depending on the amount: If you receive educational assistance benefits from your employer under an educational assistance program, you can exclude up to $5,250 of those benefits each year. This means your employer should not include those benefits with your wages, tips, and other compensation shown in box 1 of your Form W-2. This also means that you do not have to include the benefits on your income tax return. source: http://www.irs.gov/publications/p970/ch11.html However, your situation is a bit trickier since they are sort of retroactively paying for your education. I'd think the answer is \"\"Maybe\"\" and you should consult a tax professional since it is a gray area. Update: On further research, I'm going to downgrade that \"\"Maybe\"\" to \"\"Probably not, but hopefully soon.\"\" The reason I am doing so is that there is a bill in Congress specifically to allow what you are asking, which presumes that you currently can't do this. The Bill is HR Bill 395 \"\"The Student Loan Employment Benefits Act of 2013\"\" sponsored by rep Steve Israel (D). It has co-sponsors from both parties, so that is promising for it's passage, I suppose. However, it appears to be still early in the legislative process. If this issue is near/dear to your heart maybe you should call your congressman. Summary of the Bill: (from govtrack.us) Student Loan Employment Benefits Act of 2013 - Amends the Internal Revenue Code to exclude from the gross income of an employee amounts paid by an employer under a student loan payment assistance program. Limits the amount of such exclusion to $5,000 in a taxable year. Requires an employer student loan payment assistance program to be a separate written plan of an employer to provide employees with student loan payment assistance. Defines \"\"student loan payment assistance\"\" as the payment of principal or interest on any indebtedness incurred by an employee solely to pay qualified higher education expenses which are paid or incurred within a reasonable time before or after such indebtedness was incurred and are attributable to education furnished during a period in which such employee was a student eligible for federal financial assistance.\"", "title": "" } ]
PLAIN-1744	Obama	[ { "docid": "MED-4791", "text": "Dietary consumption of fish is widely recommended because of the beneficial effects of omega-3 polyunsaturated fatty acids on the risks of cardiovascular and Alzheimer's diseases. The American Heart Association currently recommends eating at least two servings of fish per week. We are concerned that consumption of farmed fish may provide a means of transmission of infectious prions from cows with bovine spongiform encephalopathy to humans, causing variant Creutzfeldt Jakob disease.", "title": "Bovine spongiform encephalopathy and aquaculture." }, { "docid": "MED-4792", "text": "In transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). While the precise mechanism of the PrPC to PrPSc conversion is not understood, it is clear that host PrPC expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish. Here we show that while gilthead sea bream (Sparus aurata) orally challenged with brain homogenates prepared either from a BSE infected cow or from scrapie infected sheep developed no clinical prion disease, the brains of TSE-fed fish sampled two years after challenge did show signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs. Remarkably, the deposits developed much more rapidly and extensively in fish inoculated with BSE-infected material than in the ones challenged with the scrapie-infected brain homogenate, with numerous deposits being proteinase K-resistant. These plaque-like aggregates exhibited congophilia and birefringence in polarized light, consistent with an amyloid-like component. The neurodegeneration and abnormal deposition in the brains of fish challenged with prion, especially BSE, raises concerns about the potential risk to public health. As fish aquaculture is an economically important industry providing high protein nutrition for humans and other mammalian species, the prospect of farmed fish being contaminated with infectious mammalian PrPSc, or of a prion disease developing in farmed fish is alarming and requires further evaluation.", "title": "Evaluation of the Possible Transmission of BSE and Scrapie to Gilthead Sea Bream (Sparus aurata)" } ]	[ { "docid": "MED-728", "text": "In a 1995 pivotal study, Kushner described the attitudes, practice behaviors, and barriers to the delivery of nutrition counseling by primary care physicians. This article recognized nutrition and dietary counseling as key components in the delivery of preventive services by primary care physicians. Kushner called for a multifaceted approach to change physicians' counseling practices. The prevailing belief today is that little has changed. Healthy People 2010 and the U.S. Preventive Task Force identify the need for physicians to address nutrition with patients. The 2010 objective was to increase to 75% the proportion of office visits that included ordering or providing diet counseling for patients with a diagnosis of cardiovascular disease, diabetes, or hypertension. At the midcourse review, the proportion actually declined from 42% to 40%. Primary care physicians continue to believe that providing nutrition counseling is within their realm of responsibility. Yet the gap remains between the proportion of patients who physicians believe would benefit from nutrition counseling and those who receive it from their primary care physician or are referred to dietitians and other healthcare professionals. The barriers cited in recent years continue to be those listed by Kushner: lack of time and compensation and, to a lesser extent, lack of knowledge and resources. The 2010 Surgeon General's Vision for a Healthy and Fit Nation and First Lady Obama's \"Let's Move Campaign\" spotlight the need for counseling adults and children on diet and physical activity.", "title": "Barriers to providing nutrition counseling cited by physicians: a survey of primary care practitioners." }, { "docid": "MED-5124", "text": "Background Reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Although eggs are important sources of cholesterol and other nutrients, limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality. Objectives To examine the association between egg consumption and the risk of CVD and mortality. Design Prospective cohort study of 21,327 participants from the Physicians' Health Study I. Egg consumption was assessed using a simple abbreviated food questionnaire. We used Cox regression to estimate relative risks. Results After an average follow up of 20 years, a total of 1,550 new myocardial infarction (MI), 1,342 incident strokes, and 5,169 deaths occurred in this cohort. Egg consumption was not associated with incident MI or stroke in a multivariable Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87-1.02), 1.03 (0.95-1.11), 1.05 (0.93-1.19), and 1.23 (1.11-1.36) for egg consumption of <1, 1, 2-4, 5-6, and 7+ per week, respectively, (p for trend <0.0001). This association was stronger among diabetic subjects with a 2-fold increased risk of death comparing the highest to the lowest category of egg consumption than non-diabetic subjects (HR: 1.22 (1.09-1.35) (p for interaction 0.09). Conclusions Our data suggest that infrequent egg consumption does not influence the risk of CVD and only confers a modest increased risk for total mortality in male physicians. In addition, egg consumption was positively related to mortality and such relation was stronger among diabetic subjects in this selective population.", "title": "Egg Consumption and Cardiovascular Disease and Mortality The Physicians' Health Study" }, { "docid": "MED-965", "text": "Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED). ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body’s vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.", "title": "Endothelial dysfunction: the early predictor of atherosclerosis" }, { "docid": "MED-1467", "text": "Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the \"culprits\" were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount. Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties. Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance. There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear. Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.", "title": "Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots." }, { "docid": "MED-1190", "text": "The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.", "title": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae." }, { "docid": "MED-5197", "text": "BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.", "title": "Cooked meat and risk of breast cancer--lifetime versus recent dietary intake." }, { "docid": "MED-4162", "text": "Large numbers of US women stopped taking hormone therapies (HT), especially estrogen/progestin (EP) formulations, after the Women's Health Initiative trial detected elevated risks of breast cancer in EP users and was halted in July 2002. Recent reports have indicated substantial and significant declines in population-based breast cancer incidence, particularly hormone-sensitive forms, for 2003 and 2004. Are these events linked? This commentary considers the available evidence linking the mass cessation of HT in 2002 to the breast cancer incidence declines of 2003/2004 and quantifies the potential impact of the cessation on the overall burden of breast cancer in the US.", "title": "Declines in breast cancer after the WHI: apparent impact of hormone therapy." }, { "docid": "MED-5052", "text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.", "title": "Can green tea do that? A literature review of the clinical evidence." }, { "docid": "MED-1637", "text": "Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.", "title": "Black tea increases coronary flow velocity reserve in healthy male subjects." }, { "docid": "MED-2180", "text": "Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.", "title": "Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study" }, { "docid": "MED-3695", "text": "BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population. OBJECTIVES: To assess the efficacy and adverse effects of probiotics (any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children. To assess adverse events associated with the use of probiotics when co-administered with antibiotics in children. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, CINAHL , AMED, and the Web of Science (inception to August 2006) were searched along with specialized registers including the Cochrane IBD/FBD Review Group, CISCOM, Chalmers PedCAM Research Register and trial registries from inception to 2005. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were hand searched. SELECTION CRITERIA: Randomized, parallel, controlled (placebo, active, or no treatment) trials comparing co-administered probiotics with antibiotics for the prevention of diarrhea secondary to antibiotic use in children (0 to 18 years). DATA COLLECTION AND ANALYSIS: Methodological quality assessment and data extraction were conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of diarrhea, adverse events) were combined using pooled relative risks, and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. Adverse events were summarized using risk difference. For overall pooled results on the incidence of diarrhea, a priori sensitivity analyses included per protocol versus intention to treat, random versus fixed effects, and methodological quality criterion. Subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, and antibiotic agent. MAIN RESULTS: Ten studies met the inclusion criteria. Trials included treatment with either Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination. Six studies used a single strain probiotic agent and four combined two probiotic strains. The per protocol analysis for 9/10 trials reporting on the incidence of diarrhea show statistically significant results favouring probiotics over active/non active controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis showed non-significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of ten trials monitored for adverse events (n = 647); none reported a serious adverse event. AUTHORS' CONCLUSIONS: Probiotics show promise for the prevention of pediatric AAD. While per protocol analysis yields treatment effect estimates that are both statistically and clinically significant, as does analysis of high quality studies, the estimate from the intention to treat analysis was not statistically significant. Future studies should involve probiotic strains and doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days). Future trials would benefit from a validated primary outcome measure for antibiotic-associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.", "title": "Probiotics for the prevention of pediatric antibiotic-associated diarrhea." }, { "docid": "MED-1172", "text": "Background The widespread use of organophosphorus (OP) pesticides has led to frequent exposure in adults and children. Because such exposure may cause adverse health effects, particularly in children, the sources and patterns of exposure need to be studied further. Objectives We assessed young urban/suburban children’s longitudinal exposure to OP pesticides in the Children’s Pesticide Exposure Study (CPES) conducted in the greater Seattle, Washington, area, and used a novel study design that allowed us to determine the contribution of dietary intake to the overall OP pesticide exposure. Methods Twenty-three children 3–11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003–2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. We measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. Results By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. We also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. Conclusions The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.", "title": "Dietary Intake and Its Contribution to Longitudinal Organophosphorus Pesticide Exposure in Urban/Suburban Children" }, { "docid": "MED-3465", "text": "Blueberries are rich in antioxidants known as anthocyanins, which may exhibit significant health benefits. Strenous exercise is known to acutely generate oxidative stress and an inflammatory state, and serves as an on-demand model to test antioxidant and anti-inflammatory compounds. The purpose of this study was to examine whether 250 g of blueberries per day for 6 weeks and 375 g given 1 h prior to 2.5 h of running at ∼72% maximal oxygen consumption counters oxidative stress, inflammation, and immune changes. Twenty-five well-trained subjects were recruited and randomized into blueberry (BB) (N = 13) or control (CON) (N = 12) groups. Blood, muscle, and urine samples were obtained pre-exercise and immediately postexercise, and blood and urine 1 h postexercise. Blood was examined for F₂-isoprostanes for oxidative stress, cortisol, cytokines, homocysteine, leukocytes, T-cell function, natural killer (NK), and lymphocyte cell counts for inflammation and immune system activation, and ferric reducing ability of plasma for antioxidant capacity. Muscle biopsies were examined for glycogen and NFkB expression to evaluate stress and inflammation. Urine was tested for modification of DNA (8-OHDG) and RNA (5-OHMU) as markers of nucleic acid oxidation. A 2 (treatment) × 3 (time) repeated measures ANOVA was used for statistical analysis. Increases in F₂-isoprostanes and 5-OHMU were significantly less in BB and plasma IL-10 and NK cell counts were significantly greater in BB vs. CON. Changes in all other markers did not differ. This study indicates that daily blueberry consumption for 6 weeks increases NK cell counts, and acute ingestion reduces oxidative stress and increases anti-inflammatory cytokines.", "title": "Effect of blueberry ingestion on natural killer cell counts, oxidative stress, and inflammation prior to and after 2.5 h of running." }, { "docid": "MED-4639", "text": "Low fecal weight and slow bowel transit time are thought to be associated with bowel cancer risk, but few published data defining bowel habits in different communities exist. Therefore, data on stool weight were collected from 20 populations in 12 countries to define this risk more accurately, and the relationship between stool weight and dietary intake of nonstarch polysaccharides (NSP) (dietary fiber) was quantified. In 220 healthy U.K. adults undertaking careful fecal collections, median daily stool weight was 106 g/day (men, 104 g/day; women, 99 g/day; P = 0.02) and whole-gut transit time was 60 hours (men, 55 hours; women, 72 hours; P = 0.05); 17% of women, but only 1% of men, passed < 50 g stool/day. Data from other populations of the world show average stool weight to vary from 72 to 470 g/day and to be inversely related to colon cancer risk (r = -0.78). Meta-analysis of 11 studies in which daily fecal weight was measured accurately in 26 groups of people (n = 206) on controlled diets of known NSP content shows a significant correlation between fiber intake and mean daily stool weight (r = 0.84). Stool weight in many Westernized populations is low (80-120 g/day), and this is associated with increased colon cancer risk. Fecal output is increased by dietary NSP. Diets characterized by high NSP intake (approximately 18 g/day) are associated with stool weights of 150 g/day and should reduce the risk of bowel cancer.", "title": "Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)" }, { "docid": "MED-2714", "text": "Aromatherapy is becoming increasingly popular; however there are few clear indications for its use. To systematically review the literature on aromatherapy in order to discover whether any clinical indication may be recommended for its use, computerised literature searches were performed to retrieve all randomised controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE, British Nursing Index, CISCOM, and AMED. The methodological quality of the trials was assessed using the Jadad score. All trials were evaluated independently by both authors and data were extracted in a pre-defined, standardised fashion. Twelve trials were located: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These studies suggest that aromatherapy massage has a mild, transient anxiolytic effect. Based on a critical assessment of the six studies relating to relaxation, the effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. The hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials.", "title": "Aromatherapy: a systematic review." }, { "docid": "MED-1785", "text": "We tested the hypothesis that 75 g of whole-shelled walnuts/day added to the Western-style diet of healthy young men would beneficially affect semen quality. A randomized, parallel two-group dietary intervention trial with single-blind masking of outcome assessors was conducted with 117 healthy men, age 21-35 yr old, who routinely consumed a Western-style diet. The primary outcome was improvement in conventional semen parameters and sperm aneuploidy from baseline to 12 wk. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. The group consuming walnuts (n = 59) experienced improvement in sperm vitality, motility, and morphology, but no change was seen in the group continuing their usual diet but avoiding tree nuts (n = 58). Comparing differences between the groups from baseline, significance was found for vitality (P = 0.003), motility (P = 0.009), and morphology (normal forms; P = 0.04). Serum FA profiles improved in the walnut group with increases in omega-6 (P = 0.0004) and omega-3 (P = 0.0007) but not in the control group. The plant source of omega-3, alpha-linolenic acid (ALA) increased (P = 0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (Spearman correlation, -0.41, P = 0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology.", "title": "Walnuts improve semen quality in men consuming a Western-style diet: randomized control dietary intervention trial." }, { "docid": "MED-4837", "text": "BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.", "title": "Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal." }, { "docid": "MED-5074", "text": "Cooking as a domestic processing method has a great impact on food nutrients. Most Brassica (Brassicaceae, Cruciferae) vegetables are mainly consumed after being cooked, and cooking considerably affects their health-promoting compounds (specifically, glucosinolates, phenolic compunds, minerals, and vitamin C studied here). The microwave cooking process presents controversial results in the literature due to the different conditions that are employed (time, power, and added water). Therefore, the aim of this work was to study the influence of these conditions during microwave cooking on the human bioactive compounds of broccoli. The results show a general decrease in the levels of all the studied compounds except for mineral nutrients which were stable under all cooking conditions. Vitamin C showed the greatest losses mainly because of degradation and leaching, whereas losses for phenolic compounds and glucosinolates were mainly due to leaching into water. In general, the longest microwave cooking time and the higher volume of cooking water should be avoided to minimize losses of nutrients.", "title": "Effects of microwave cooking conditions on bioactive compounds present in broccoli inflorescences." }, { "docid": "MED-3012", "text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment." }, { "docid": "MED-5250", "text": "Several prospective studies considered the relation between coffee consumption and mortality. Most studies, however, were underpowered to detect an association, since they included relatively few deaths. To obtain quantitative overall estimates, we combined all published data from prospective studies on the relation of coffee with mortality for all causes, all cancers, cardiovascular disease (CVD), coronary/ischemic heart disease (CHD/IHD) and stroke. A bibliography search, updated to January 2013, was carried out in PubMed and Embase to identify prospective observational studies providing quantitative estimates on mortality from all causes, cancer, CVD, CHD/IHD or stroke in relation to coffee consumption. A systematic review and meta-analysis was conducted to estimate overall relative risks (RR) and 95 % confidence intervals (CI) using random-effects models. The pooled RRs of all cause mortality for the study-specific highest versus low (≤1 cup/day) coffee drinking categories were 0.88 (95 % CI 0.84-0.93) based on all the 23 studies, and 0.87 (95 % CI 0.82-0.93) for the 19 smoking adjusting studies. The combined RRs for CVD mortality were 0.89 (95 % CI 0.77-1.02, 17 smoking adjusting studies) for the highest versus low drinking and 0.98 (95 % CI 0.95-1.00, 16 studies) for the increment of 1 cup/day. Compared with low drinking, the RRs for the highest consumption of coffee were 0.95 (95 % CI 0.78-1.15, 12 smoking adjusting studies) for CHD/IHD, 0.95 (95 % CI 0.70-1.29, 6 studies) for stroke, and 1.03 (95 % CI 0.97-1.10, 10 studies) for all cancers. This meta-analysis provides quantitative evidence that coffee intake is inversely related to all cause and, probably, CVD mortality.", "title": "A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases." }, { "docid": "MED-2436", "text": "The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients.", "title": "Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients." }, { "docid": "MED-3619", "text": "Diagnostic imaging is an indispensable part of contemporary medical and dental practice. Over the last few decades there has been a dramatic increase in the use of ionizing radiation for diagnostic imaging. The carcinogenic effects of high-dose exposure are well known. Does diagnostic radiation rarely cause cancer? We don't know but we should act as if it does. Accordingly, dentists should select patients wisely - only make radiographs when there is patient-specific reason to believe there is a reasonable expectation the radiograph will offer unique information influencing diagnosis or treatment. Low-dose examinations should be made: intraoral imaging - use fast film or digital sensors, thyroid collars, rectangular collimation; panoramic and lateral cephalometric imaging - use digital systems or rare-earth film screen combinations; and cone beam computed tomography - use low-dose machines, restrict field size to region of interest, reduce mA and length of exposure arc as appropriate. © 2012 Australian Dental Association.", "title": "Update on the biological effects of ionizing radiation, relative dose factors and radiation hygiene." }, { "docid": "MED-3100", "text": "Dioxins invade the body mainly through the diet, and produce toxicity through the transformation of aryl hydrocarbon receptor (AhR). An inhibitor of the transformation should therefore protect against the toxicity and ideally be part of the diet. We examined flavonoids ubiquitously expressed in plant foods as one of the best candidates, and found that the subclasses flavones and flavonols suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8-tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform AhR. The antagonistic IC(50) values ranged from 0.14 to 10 microM, close to the physiological levels in human.", "title": "Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin." }, { "docid": "MED-4560", "text": "The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.", "title": "Preventing and arresting coronary atherosclerosis." }, { "docid": "MED-5171", "text": "The objective of this study was to determine the prevalence of enterohemorrhagic Escherichia coli (EHEC), E. coli O157, Salmonella, and Listeria monocytogenes in retail food samples from Seattle, Wash. A total of 2,050 samples of ground beef (1,750 samples), mushrooms (100 samples), and sprouts (200 samples) were collected over a 12-month period and analyzed for the presence of these pathogens. PCR assays, followed by culture confirmation were used to determine the presence or absence of each organism. Of the 1,750 ground beef samples analyzed, 61 (3.5%) were positive for EHEC, and 20 (1.1%) of these were positive for E. coli O157. Salmonella was present in 67 (3.8%) of the 1,750 ground beef samples. Of 512 ground beef samples analyzed, 18 (3.5%) were positive for L. monocytogenes. EHEC was found in 12 (6.0%) of the 200 sprout samples, and 3 (1.5%) of these yielded E. coli O157. Of the 200 total sprout samples, 14 (7.0%) were positive for Salmonella and none were positive for L. monocytogenes. Among the 100 mushroom samples, 4 (4.0%) were positive for EHEC but none of these 4 samples were positive for E. coli O157. Salmonella was detected in 5 (5.0%) of the mushroom samples, and L. monocytogenes was found in 1 (1.0%) of the samples.", "title": "Incidence of enterohemorrhagic Escherichia coli, Escherichia coli O157, Salmonella, and Listeria monocytogenes in retail fresh ground beef, sprouts..." }, { "docid": "MED-3734", "text": "Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.", "title": "Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants." }, { "docid": "MED-1037", "text": "Ancient Egypt was one of the greatest civilizations to have arisen, becoming the cradle of scientific enquiry and social development over 3 millennia; undoubtedly its knowledge of medicine has been vastly underestimated. Few artefacts survive which describe the medical organization, but from the extent of the diseases afflicting that ancient populus there would have been much to study. Evidence from papyri, tomb bas reliefs and the writings of historians of antiquity tell of an intense interest in the sciences, humanities and medicine born of an educated society which had overcome the superstitions of its nomadic ancestors.", "title": "A brief journey into medical care and disease in ancient Egypt." }, { "docid": "MED-3102", "text": "BACKGROUND: Halogenated aromatic hydrocarbons including dioxins and non-halogenated polycyclic aromatic hydrocarbons are ligands of an aryl hydrocarbon receptor (AhR) and stimulate its transformation. Exposure to these environmental contaminants occurs mainly through diet. Recent articles demonstrated that certain food factors regulate the AhR transformation and expression of downstream drug-metabolizing enzymes. OBJECTIVE: To explain the actions of these food factors on the AhR transformation, as the mechanisms underlying are not fully understood. METHODS: This review introduces recent articles that have demonstrated the molecular mechanisms by which food factors regulate the AhR transformation and downstream drug-metabolizing enzymes. RESULTS/CONCLUSION: The role of classical ligands including dioxins as agonists of the receptor is well documented. As to the food factors, they act as antagonists because they basically suppress the AhR transformation by different mechanisms. Moreover, the fate and metabolism of food factors are important to understand their mechanisms.", "title": "An update on the dietary ligands of the AhR." }, { "docid": "MED-1345", "text": "This article explores the reaction when an article challenging received wisdom is published and covered extensively by the media (1). The article in question was a meta-analysis of antidepressant clinical trials indicating that for most patients, difference between drug and placebo was not clinically significant. Reactions ranged from denial that the effects of antidepressants are so small to criticisms of the clinical trials that were analyzed. Each of these reactions is explored and countered.", "title": "Challenging Received Wisdom: Antidepressants and the Placebo Effect" }, { "docid": "MED-2819", "text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.", "title": "Biological actions of curcumin on articular chondrocytes." } ]
7956	Some stock's prices don't fluctuate widely - Is it an advantages?	[ { "docid": "293027", "text": "What is your investment goal? Many investors buy for the long haul, not short-term gain. If you're looking for long-term gain then daily fluctuations should be of no concern to you. If you want to day-trade and time the market (buy low and sell high with a short holding period) then yes less volatile stock can be less profitable, but they also carry less risk. In that case, though, transaction fees have more of an impact, and you usually have to trade in larger quantities to reduce the impact of transaction fees.", "title": "" }, { "docid": "483765", "text": "Oracle specifically is paying a dividend with a current yield of about 1.4% annually and has appreciated nearly 50% over the last 5 years. Granted, the past doesn't guarantee the future but the company has paid a pretty steady dividend since 2009. If you're buying as part of an employee program you would presumably be holding the shares for a long time and the daily and even monthly movements aren't terribly relevant to a long term holding period. Additionally, you may be able to buy the shares at a discount to the market price as part of your employee program. You probably also won't pay any transaction fee.", "title": "" }, { "docid": "127702", "text": "I don't think you are reading the stock chart right. ORCL has a beta of 1.12 which means it has more volatility than the market as a whole. See image below for a fairly wild stock chart for a year. I would not truly consider ESPP participation investing, unless you intend to buy and hold the stock. If you intend to sell the stock soon after you are able, it is more speculation. ESPP's are okay based upon the terms. If the stock was a constant price, and you could sell right away, then an ESPP plan would be easy money. Often, employees are often given a 15% discount to purchase the stock. If you can sell it before any price drop, then you are guaranteed to make 15% on the money invested minus any commissions. Some employers make ESPP participants hold the stock for a year. This makes such a plan less of a value. The reasons are the stock can drop in price during that time, you could need the money, or (in the best case) your money is tied up longer making the ROI less. The reasons people invest in stock are varied and is far to much to discuss in a single post. Some of your colleagues are using the ESPP solely to earn the discount in their money.", "title": "" }, { "docid": "598295", "text": "Apart from making money from the price difference, some stocks also give dividends, or bonus issues. For long term investors whom are looking for steady income, they may be more interested with the dividend pay-out instead of the capital-appreciation.", "title": "" } ]	[ { "docid": "127689", "text": "\"I think this is a good question with no single right answer. For a conservative investor, possible responses to low rates would be: Probably the best response is somewhere in the middle: consider riskier investments for a part of your portfolio, but still hold on to some cash, and in any case do not expect great results in a bad economy. For a more detailed analysis, let's consider the three main asset classes of cash, bonds, and stocks, and how they might preform in a low-interest-rate environment. (By \"\"stocks\"\" I really mean mutual funds that invest in a diversified mixture of stocks, rather than individual stocks, which would be even riskier. You can use mutual funds for bonds too, although diversification is not important for government bonds.) Cash. Advantages: Safe in the short term. Available on short notice for emergencies. Disadvantages: Low returns, and possibly inflation (although you retain the flexibility to move to other investments if inflation increases.) Bonds. Advantages: Somewhat higher returns than cash. Disadvantages: Returns are still rather low, and more vulnerable to inflation. Also the market price will drop temporarily if rates rise. Stocks. Advantages: Better at preserving your purchasing power against inflation in the long term (20 years or more, say.) Returns are likely to be higher than stocks or bonds on average. Disadvantages: Price can fluctuate a lot in the short-to-medium term. Also, expected returns are still less than they would be in better economic times. Although the low rates may change the question a little, the most important thing for an investor is still to be familiar with these basic asset classes. Note that the best risk-adjusted reward might be attained by some mixture of the three.\"", "title": "" }, { "docid": "329527", "text": "The problem with predicting with accuracy what a stock price will do in any given situation is that there are two main factors that affect a stocks price. The first factor is based somewhat in math as it takes into account numbers such as supply and demand, earnings per share, expected earnings, book value, debt ratio and a wide variety of other numbers. You can compile all those numbers into a variety of formulas and come up with a rational estimate of what the stock should sell for. This is all well and good and if the market were entirely rational it would rarely make news because it would be predictable and boring. This is where our second factor throws a wrench in the works. The second factor affecting stock price is emotional. There are many examples of people's emotions affecting stock price but if you would like a good example look up the price fluctuations of Apple (AAPL) after their last couple earnings reports. Numerically their company looks good, their earnings were healthy, their EPS is below average yet their price fell following the report. Why is that? There really isn't a rational reason for it, it is driven by the emotions behind unmet expectations. In a more general sense sometimes price goes down and people get scared and sell causing further decline, sometimes people get excited and see it as opportunity to buy in and the price stabilizes. It is much more difficult to anticipate the reaction the market will have to people's emotional whims which is why predicting stock price with accuracy is near impossible. As a thought along the same line ask yourself this question; if the stock market were entirely rational and price could be predicted with accuracy why is there such a wide range of available strike prices available in the options market? It seems that if stock price could be predicted with anything remotely reassembling accuracy the options market need a much smaller selection of available strike prices.", "title": "" }, { "docid": "446629", "text": "Algorithmic trading essentially banks on the fact that a price will fluctuate in tiny amounts over short periods of time, meaning the volatility is high in that given time frame. As the time frame increases the efficiency of algorithmic trading decreases and proper investment strategies such as due diligence, stock screening, and technical analysis become the more efficient methods. Algorithms become less effective as the time frame increases due to the smoothing effect of volatility over time. Writing an algorithm that could predict future long-term prices would be an impossible feat because as the time frame is scaled up there are far less price fluctuations and trends (volatility smooths out) and so there is little to no benchmark for the formulas. An algorithm simply wouldn't make sense for a long-term position. A computer can't predict, say, the next quarter, an ousted CEO, a buyout, or anything else that could effect the price of the security, never mind the psychology behind it all. Vice versa, researching a company's fundamentals just to bank on a 0.25% daily swing would not be efficient. Tax advantages or not, it is the most efficient methods that are preferred for a given time-scale of trading.", "title": "" }, { "docid": "433516", "text": "The time horizon is usually very short for a home down payment. I would use Certificates of Deposit (CDs) with a short maturity (in the horizon of your intended use) or Money Market accounts. Depending on what the interests rates are where you are looking. You don't want the money in the market 100% (i.e. stocks) as the fluctuations might be too wide around the time you intend to pull the money out (and that will be soon).", "title": "" }, { "docid": "197047", "text": "Ok you're looking at this in a very confusing way. First, as said by CapitalNumb3rs, the dividend yield is the dividends paid in the year as a percent of the stock price. Given this fact then if the stock price moves down and the dividend stays the same then the yield increases. Company's don't usually pay out on a yield basis, that's mostly just a calculation to measure how strong a dividend is. This could mean either A. The stock is underpriced and will rise which will lower the yield to a more normal level or B. the company is not doing as well and eventually the dividends will decrease to a point where the yield again looks more normal. Second off let's look at it in a more realistic way that still takes into account your assumptions: YEAR 1 1. Instead of assuming buying 35% let's put this into a share amount. Let's say there are 1,000,000 shares so you just bought 350k shares for $700k. You paid a price of $2/share. Let's assume the market decides that's a fair price and it stays that way through the end of year 1. This gives us a market capitalization of $2 million. 2. The dividend paid out at year 1 is $60k so you could calculate on a per share basis which would be a dividend of $60k / 1 million shares or a $0.06 dividend per share. Our stock price is still at $2.00 so our yield comes out to $0.06 / $2.00 or 3.0% YEAR 2 Assuming no additional shares issued there are still a total of 1 million shares outstanding. You owned 350k and now want to purchase another 50k (5% of outstanding share float). The market price you are able to purchase the 50k shares at has now changed which means that share price is now valued at $1.50 / share. We have a dividend paid out at $100k, which comes out to a dividend per share of $0.10. We have a share value of $1.50 and the $0.10 dividend per share giving us a new yield of 6.66%. CONCLUSION: There are many factors that can cause a company's stock price to fluctuate, some of it is hype based but some of it is a result of material changes. In your case the stock went down 25%. In most scenarios where a stock would have that much decline it would likely either not have been paying a dividend in the first place or would maybe not be paying one for much longer. Most companies that pay dividends are larger and more mature companies with a steady, healthy and predictable cash flow. Also most companies that are that size would not trade a stock under $3.00, I know this is just an example but the scenario is definitely a bit extreme in terms of the price drop and dividend increase. Again the yield is just a calculation that depends on the dividend that is usually planned in advance and the stock price that can fluctuate for many reasons. I hope this made everything more clear and let me know if you have any other questions.", "title": "" }, { "docid": "519390", "text": "\"Wouldn't this be part of your investing strategy to know what price is considered a \"\"good\"\" price for the stock? If you are going to invest in company ABC, shouldn't you have some idea of whether the stock price of $30, $60, or $100 is the bargain price you want? I'd consider this part of the due diligence if you are picking individual stocks. Mutual funds can be a bit different in automatically doing fractional shares and not quite as easy to analyze as a company's financials in a sense. I'm more concerned with the fact that you don't seem to have a good idea of what the price is that you are willing to buy the stock so that you take advantage of the volatility of the market. ETFs would be similar to mutual funds in some ways though I'd probably consider the question that may be worth considering here is how much do you want to optimize the price you pay versus adding $x to your position each time. I'd probably consider estimating a ballpark and then setting the limit price somewhere within that. I wouldn't necessarily set it to the maximum price you'd be willing to pay unless you are trying to ride a \"\"hot\"\" ETF using some kind of momentum strategy. The downside of a momentum strategy is that it can take a while to work out the kinks and I don't use one though I do remember a columnist from MSN Money that did that kind of trading regularly.\"", "title": "" }, { "docid": "184077", "text": "\"Your employer sends the money that you choose to contribute, plus employer match if any, to the administrator of the 401k plan who invests the money as you have directed, choosing between the alternatives offered by the administrator. Typically, the alternatives are several different mutual funds with different investment styles, e.g. a S&P 500 index fund, a bond fund, a money-market fund, etc. Now, a statement such as \"\"I see my 401k is up 10%\"\" is meaningless unless you tell us how you are making the comparison. For example, if you have just started employment and $200 goes into your 401k each month and is invested in a money-market fund (these are paying close to 0% interest these days), then your 11th contribution increases your 401k from $2000 to $2200 and your 401k is \"\"up 10%\"\". More generally, suppose for simplicity that all the 401k investment is in just one (stock) mutual fund and that you own 100 shares of the fund as of right now. Suppose also that your next contribution will not occur for three weeks when you get your next paycheck, at which time additional shares of the mutual fund will be purchased Now, the value of the mutual fund shares (often referred to as net asset value or NAV) fluctuates as stock prices rise and fall, and so the 401k balance = number of shares times NAV changes in accordance with these fluctuations. So, if the NAV increases by 10% in the next two weeks, your 401k balance will have increased by 10%. But you still own only 100 shares of the mutual fund. You cannot use the 10% increase in value to buy more shares in the mutual fund because there is no money to pay for the additional shares you wish to purchase. Notice that there is no point selling some of the shares (at the 10% higher NAV) to get cash because you will be purchasing shares at the higher NAV too. You could, of course, sell shares of the stock mutual fund at the higher NAV and buy shares of some other fund available to you in the 401k plan. One advantage of doing this inside the 401k plan is that you don't have to pay taxes (now) on the 10% gain that you have made on the sale. Outside tax-deferred plans such as 401k and IRA plans, such gains would be taxable in the year of the sale. But note that selling the shares of the stock fund and buying something else indicates that you believe that the NAV of your stock mutual fund is unlikely to increase any further in the near future. A third possibility for your 401k being up by 10% is that the mutual fund paid a dividend or made a capital gains distribution in the two week period that we are discussing. The NAV falls when such events occur, but if you have chosen to reinvest the dividends and capital gains, then the number of shares that you own goes up. With the same example as before, the NAV goes up 10% in two weeks at which time a capital gains distribution occurs, and so the NAV falls back to where it was before. So, before the capital gains distribution, you owned 100 shares at $10 NAV which went up to $11 NAV (10% increase in NAV) for a net increase in 401k balance from $1000 to $1100. The mutual fund distributes capital gains in the amount of $1 per share sending the NAV back to $10, but you take the $100 distribution and plow it back into the mutual fund, purchasing 10 shares at the new $10 NAV. So now you own 110 shares at $10 NAV (no net change in price in two weeks) but your 401k balance is $1100, same as it was before the capital gains distribution and you are up 10%. Or, you could have chosen to invest the distributions into, say, a bond fund available in your 401k plan and still be up 10%, with no change in your stock fund holding, but a new investment of $100 in a bond fund. So, being up 10% can mean different things and does not necessarily mean that the \"\"return\"\" can be used to buy more shares.\"", "title": "" }, { "docid": "30774", "text": "The biggest challenge with owning any individual stock is price fluctuation, which is called risk. The scenarios you describe assume that the stock behaves exactly as you predict (price/portfolio doubles) and you need to consider risk. One way to measure risk in a stock or in a portfolio is Sharpe Ratio (risk adjusted return), or the related Sortino ratio. One piece of advice that is often offered to individual investors is to diversify, and the stated reason for diversification is to reduce risk. But that is not telling the whole story. When you are able to identify stocks that are not price correlated, you can construct a portfolio that reduces risk. You are trying to avoid 10% tax on the stock grant (25%-15%), but need to accept significant risk to avoid the 10% differential tax ($1000). An alternative to a single stock is to invest in an ETF (much lower risk), which you can buy and hold for a long time, and the price/growth of an ETF (ex. SPY) can be charted versus your stock to visualize the difference in growth/fluctuation. Look up the beta (volatility) of your stock compared to SPY (for example, IBM). Compare the beta of IBM and TSLA and note that you may accept higher volatility when you invest in a stock like Tesla over IBM. What is the beta of your stock? And how willing are you to accept that risk? When you can identify stocks that move in opposite directions, and mix your portfolio (look up beta balanced portolio), you can smooth out the variability (reduce the risk), although you may reduce your absolute return. This cannot be done with a single stock, but if you have more money to invest you could compose the rest of your portfolio to balance the risk for this stock grant, keep the grant shares, and still effectively manage risk. Some years ago I had accumulated over 10,000 shares (grants, options) in a company where I worked. During the time I worked there, their price varied between $30/share and < $1/share. I was able to liquidate at $3/share.", "title": "" }, { "docid": "508764", "text": "Mutual funds don't work like stocks in that way. The price of a mutual fund is set at the end of each day and doesn't fluctuate during the day. So no matter when you put in your order, it will be filled at the end of the day at whatever the closing price is for that day. Here is some good information on that There is no continuous pricing of fund shares throughout the trading day. When an investor places an order to buy or sell a fund's shares, the order is executed based on the NAV calculated at the end of that trading day, regardless of what time during the day the order was placed. On the other hand, if the investor were to check the price of his or her fund shares halfway through the business day, the price quoted would be the previous day's NAV because that was the last time the fund calculated and reported the value. -http://www.finweb.com/investing/how-mutual-funds-are-priced.html", "title": "" }, { "docid": "473658", "text": "ETFs offer the flexibility of stocks while retaining many of the benefits of mutual funds. Since an ETF is an actual fund, it has the diversification of its potentially many underlying securities. You can find ETFs with stocks at various market caps and style categories. You can have bond or mixed ETFs. You can even get ETFs with equal or fundamental weighting. In short, all the variety benefits of mutual funds. ETFs are typically much less expensive than mutual funds both in terms of management fees (expense ratio) and taxable gains. Most of them are not actively managed; instead they follow an index and therefore have a low turnover. A mutual fund may actively trade and, if not balanced with a loss, will generate capital gains that you pay taxes on. An ETF will produce gains only when shifting to keep inline with the index or you yourself sell. As a reminder: while expense ratio always matters, capital gains and dividends don't matter if the ETF or mutual fund is in a tax-advantaged account. ETFs have no load fees. Instead, because you trade it like a stock, you will pay a commission. Commissions are straight, up-front and perfectly clear. Much easier to understand than the various ways funds might charge you. There are no account minimums to entry with ETFs, but you will need to buy complete shares. Only a few places allow partial shares. It is generally harder to dollar-cost average into an ETF with regular automated investments. Also, like trading stocks, you can do those fancy things like selling short, buying on margin, options, etc. And you can pay attention to the price fluctuations throughout the day if you really want to. Things to make you pause: if you buy (no-load) mutual funds through the parent company, you'll get them at no commission. Many brokerages have No Transaction Fee (NTF) agreements with companies so that you can buy many funds for free. Still look out for that expense ratio though (which is probably paying for that NTF advantage). As sort of a middle ground: index funds can have very low expense ratios, track the same index as an ETF, can be tax-efficient or tax-managed, free to purchase, easy to dollar-cost average and easier to automate/understand. Further reading:", "title": "" }, { "docid": "16292", "text": "I asked a friend and he gave me a good explanation, so I'm just gonna paste it here for others: There is a simple and a complex answer depending on how much you want to understand the pricing dynamic of options. LEAPs don't react 1:1 with a stock move because the probability of your option being in the money at expiry is still very much up in the air so you basically don't get full credit for a move in the stock this far out from expiry. The more complex answer involves a discussion of option 'greeks'. Delta, Gamma, Theta, Vega, and Rho are variables that affect the pricing of all options. The key greek in this case is Delta because it describes mathematically the expected move of an option as a ratio vs changes in stock price. For put options the ratio is -1 to 0 where -1 is direct correlation between stock price and option price and 0 is no correlation. The Delta increases as an option gets deeper in the money and also as it gets closer to expiry and reflects the probability of the option expiring in the money. For your option contract the current Delta is -0.5673 so -3.38 * -0.5673 = 1.9 which is close. Also keep in mind that that strike price had a last trade at 12:03 when the stock was at 13.3 and the current ask price is 22.30 so the last price isn't a true reflection of the market value. As for the other greeks, Gamma is a reflection of volatility in the sense that it affects the rate of change of Delta as price and time changes. Theta is the value of the time component of the option and is expressed as the expected time decay per day. The problem is that the time premium is really some arbitrary number that the market maker seems to be able to change at will without justification and it can fluctuate wildly over short periods of time and I think this may explain some of the discrepancy. If you bought the options when AAPL was $118.68 a couple weeks ago (option price of $18.85) and now AAPL is at $112.34 and the Delta over that time averaged at -0.55 then your expected option price would be $22.34 (($118.68 - $112.34) * 0.55 + 18.85 = $22.34) so you lost around $0.24 in time premium or 'Theta burn' over the last 2 weeks assuming it opens trading around 22.1 on Monday. Your broker should have information about the option contract greeks somewhere. For my platform I have to put the cursor over top of the option contract for it to show me the greeks. If your broker doesn't have this then you can get it from nasdaq.com. This is another reason that I only invest in deep in the money LEAPs because the time premium is much much lower than near the money and also because delta is much higher so if I want to trade out of it early I don't feel like I'm getting ripped off not getting paid for a stock price move. For example look at the Jan 17 175 put. The Delta is -0.9 and the time premium is only $0-1 depending if you are looking at the bid or ask. The only downside is expected returns are lower for deep in the money contracts and they are expensive to buy.", "title": "" }, { "docid": "100546", "text": "\"A company doesn't offer up 100% of its shares to the market. There's a float amount of varying significance, maybe 30% of the shares are put up for public offer. Generally some amount of current shareholders will pledge some or all of their shares for offer to the public. This may be how the venture capital, private equity or other current investors cash out their initial investment. The company may issue new shares in order to raise money for some initiative. It may be a combination of existing shares and new. Additionally, a company may hold some \"\"treasury shares\"\" on its balance sheet. In this instance fluctuations in the share price directly affect the health of the balance sheet. As far as incentive goes, stock options to management and C-Suite employees keep everyone interested in an increasing stock price.\"", "title": "" }, { "docid": "191677", "text": "10-Q is the quarterly report, and accordingly is filed quarterly. Similarly, 10-K is the annual report. 8-K is a general form for notification of material events. It is filed every time a material event is required to be reported to the shareholders. It may accompany the periodical reports, but doesn't have to. It can be filed on its own. If you're only interested in the financial statements, then you should be looking for the 10K/10Q forms. SEC will tell you when the forms were filed (dates), but it won't tell you what's more material and what's less. So you can plot a stock price graph on these dates, and see what was deemed more material by the investors based on the price fluctuations, but be prepared to find fluctuations that have no correlation to filings - because the market as a whole can drag the stock up or down. Also, some events may not be required to be reported to SEC, but may be deemed material by the investors. For example, a Cupertino town hall meeting discussing the zoning for the new AAPL HQ building may be deemed material by the investors, based on the sentiments, even if no decision was made to be reported to SEC.", "title": "" }, { "docid": "583378", "text": "There's a lot of hype about HFT. It involves computers doing things that people don't really understand and making a bunch of rich guys a bunch of money, and there was a crisis and so we hate rich wall street guys this year, and so it's a hot-button issue. Meh. There's some reason for concern about the safety of the markets, but I think there's also a lot more of people trying to sell you a newspaper. Remember that while HFT may mean there are a lot of trades, the buying and the selling add up to the same thing. Meanwhile, people who buy stock to hold on to it for significant periods of time will still affect the quantity of stock out there on the market, applying pressure to the price, buying and selling at the prices that they think the security is worth. As a result, it's unlikely that high-frequency trading moves the stock price very far from the price that the rest of the market would determine for very long; if it did, the lower-frequency traders could take advantage of it, buying if it's too low and selling if it's too high. How long do you plan to hold a stock? If you're trying to do day-trading, you might have some trouble; these people are competing with you to do the same thing, and have significant resources at their disposal. If you're holding onto your stock for years on end (like you probably should be doing with most stock) then a trivial premium or discount on the price probably isn't going to be a big deal for you.", "title": "" }, { "docid": "5572", "text": "\"It's not necessarily bad but it can cause the stock price to become a lot more volatile. Depends on which side of the bet you're on ;) Suppose a hedge fund manager thinks a company is poorly run. He may buy a ton of shares so that he can get rid of the current CEO and replace it with his/her own. For the hedge fund and others long on the stock, this is good. Those who are trading options or using some short-term strategies could get screwed because of the sudden volatility. My next point is related to the above. What is the intrinsic value of a stock? The current price of a stock is the equilibrium of all investor's perception of the stock's value. Professionals make up a value for a stock using models such as DCF. Once they do so they trade based on what they believe the value of the stock is. You might calculate a stock is worth 70 and I believe it's 80 so the stock price is going to fluctuate a bit but it should keep within that range (assuming we're the only investors). Then comes a hedge fund manager, say Carl Icahn, and discloses a stake in our stock. \"\"Wow, the stock must be really valuable!\"\" Everyone starts buying this stock so up it goes to 90, simply because the guy who seems to know what he's doing bought it. The point here is that now it's not trading based on intrinsic value, now it's purely psychological. Ie. it's now a momentum stock, which you have no idea when it'll crash. Look at Tesla, Netflix, or just google momentum stocks. All the big crashes in stock prices happen when these big funds unload their stocks. A surge in supply will cut the price. The problem is you can't predict when some fund manager will decide to sell some stake of his. Tying everything together is liquidity. The more liquid a stock is, the easier it is to obtain and the less volatile it is. The more people playing the game, with not too big shares of stock, the faster the price will converge to some equilibrium and with less volatility. Institutional investors take away liquidity.\"", "title": "" }, { "docid": "288403", "text": "Earnings per share is the company profit (or loss), divided by the number of outstanding shares. The number should always be compared to the share price, so for instance if the EPS is $1 and the share price is $10, the EPS is 10% of the share price. This means that if the company keeps up this earning you should expect to make 10% yearly on your investment, long term. The stock price may fluctuate, but if the company keeps on making money you will eventually do so too as investor. If the EPS is low it means that the market expects the earnings to rise in the future, either because the company has a low profit margin that can be vastly improved, or because the business is expected to grow. Especially the last case may be a risky investment as you will lose money if the company doesn't grow fast enough, even if it does make a healthy profit. Note that the listed EPS, like most key figures, is based on the last financial statement. Recent developments could mean that better or worse is generally expected. Also note that the earnings of some companies will fluctuate wildly, for instance companies that produce movies or video games will tend to have a huge income for a quarter or two following a new release, but may be in the negative in some periods. This is fine as long as they turn a profit long term, but you will have to look at data for a longer period in order to determine this.", "title": "" }, { "docid": "329662", "text": "\"As the other answer said, the person who owns the lent stock does not benefit directly. They may benefit indirectly in that brokers can use the short lending profits to reduce their fees or in that they have the option to short other stocks at the same terms. Follow-up question: what prevents the broker lending the shares for a very short time (less than a day), pocketing the interest and returning the lenders their shares without much change in share price (because borrowing period was very short). What prevents them from doing that many times a day ? Lack of market. Short selling for short periods of time isn't so common as to allow for \"\"many\"\" times a day. Some day traders may do it occasionally, but I don't know that it would be a reliable business model to supply them. If there are enough people interested in shorting the stock, they will probably want to hold onto it long enough for the anticipated movement to happen. There are transaction costs here. Both fees for trading at all and the extra charges for short sale borrowing and interest. Most stocks do not move down by large enough amounts \"\"many\"\" times a day. Their fluctuations are smaller. If the stock doesn't move enough to cover the transaction fees, then that seller lost money overall. Over time, sellers like that will stop trading, as they will lose all their money. All that said, there are no legal blocks to loaning the stock out many times, just practical ones. If a stock was varying wildly for some bizarre reason, it could happen.\"", "title": "" }, { "docid": "415281", "text": "I agree that high volatility just means the underlying stock price fluctuates more, and it does not imply if the stock is going up or down. But a high volatility in the price of an underlying also means that there is a higher chance that the underlying price could reach extreme prices (albeit in either direction). However, if you purchased a call option then if the underlying price reached an extremely high value, then you will be richly rewarded. But if the underlying price reached an extremely low value, you won't lose any more than the initial premium that you paid. There is no additional risk on your side, it's capped to the premium that you paid for the call option. It's this asymmetric outcome (Heads - I win, Tails - I don't lose) combined with high volatility that means that call options will increase in value when the underlying price becomes more volatile. If the optionality wasn't there then the price wouldn't be related to the volatility of the underlying. But that would be called a Future or a Forward :-)", "title": "" }, { "docid": "466711", "text": "Because buying at discount provides a considerable safety of margin -- it increases the likelihood of profiting. The margin serves to cushion future adverse price movement. Why is so much effort made to get a small percentage off an investment, if one is then willing to let the investment drop another 20% or more with the reason of being in it for the long term? Nobody can predict the stock price. Now if a long term investor happens to buy some stocks and the market crashes the next day, he could afford to wait for the stock prices to bounce back. Why should he sells immediately to incur a definite loss, should he has confidence in the underlying companies to recover eventually? One can choose to buy wisely, but the market fluctuation is out of his/her control. Wouldn't you agree that he/she should spend much efforts on something that can be controlled?", "title": "" }, { "docid": "374225", "text": "\"First of all, it's great you're now taking full advantage of your employer match – i.e. free money. Next, on the question of the use of a life cycle / target date fund as a \"\"hedge\"\": Life cycle funds were introduced for hands-off, one-stop-shopping investors who don't like a hassle or don't understand. Such funds are gaining in popularity: employers can use them as a default choice for automatic enrollment, which results in more participation in retirement savings plans than if employees had to opt-in. I think life cycle funds are a good innovation for that reason. But, the added service and convenience typically comes with higher fees. If you are going to be hands-off, make sure you're cost-conscious: Fees can devastate a portfolio's performance. In your case, it sounds like you are willing to do some work for your portfolio. If you are confident that you've chosen a good equity glide path – that is, the initial and final stock/bond allocations and the rebalancing plan to get from one to the other – then you're not going to benefit much by having a life cycle fund in your portfolio duplicating your own effort with inferior components. (I assume you are selecting great low-cost, liquid index funds for your own strategy!) Life cycle are neat, but replicating them isn't rocket science. However, I see a few cases in which life cycle funds may still be useful even if one has made a decision to be more involved in portfolio construction: Similar to your case: You have a company savings plan that you're taking advantage of because of a matching contribution. Chances are your company plan doesn't offer a wide variety of funds. Since a life cycle fund is available, it can be a good choice for that account. But make sure fees aren't out of hand. If much lower-cost equity and bond funds are available, consider them instead. Let's say you had another smaller account that you were unable to consolidate into your main account. (e.g. a Traditional IRA vs. your Roth, and you didn't necessarily want to convert it.) Even if that account had access to a wide variety of funds, it still might not be worth the added hassle or trading costs of owning and rebalancing multiple funds inside the smaller account. There, perhaps, the life cycle fund can help you out, while you use your own strategy in your main account. Finally, let's assume you had a single main account and you buy partially into the idea of a life cycle fund and you find a great one with low fees. Except: you want a bit of something else in your portfolio not provided by the life cycle fund, e.g. some more emerging markets, international, or commodity stock exposure. (Is this one reason you're doing it yourself?) In that case, where the life cycle fund doesn't quite have everything you want, you could still use it for the bulk of the portfolio (e.g. 85-95%) and then select one or two specific additional ETFs to complement it. Just make sure you factor in those additional components into the overall equity weighting and adjust your life cycle fund choice accordingly (e.g. perhaps go more conservative in the life cycle, to compensate.) I hope that helps! Additional References:\"", "title": "" }, { "docid": "60001", "text": "Yes, from the point-of-view to the end speculator/investor in stocks, it is ludicrous to take on liabilities when you don't have to. That's why single-stock options are far more liquid than single-stock futures. However, if you are a farmer with a huge mortgage depending upon the chaos of agricultural markets which are extremely volatile, a different structure might appeal to you. You could long your inputs while shorting your outputs, locking in a profit. That profit is probably lower than what one could expect over the long run without hedging, but it will surely be less volatile. Here's where the advantage of futures come in for that kind of structure: the margin on the longs and shorts can offset each other, forcing the farmer to have to put up much less of one's own money to hedge. With options, this is not the case. Also, the gross margin between the inputs rarely fluctuate to an unmanageable degree, so if your shorts rise faster than your longs, you'll only have to post margin in the amount of the change in the net of the longs and shorts. This is why while options on commodities exist to satisfy speculators, futures are the most liquid.", "title": "" }, { "docid": "20079", "text": "The basic idea behind a derivative is very simple actually. It is a contract where the final value depends on (is derived from) the value of something else. Stock, for instance, is not a derivative because the contract itself is actually ownership of part of a company. Whereas car insurance is a derivative because the payout depends on the value of something else namely your (and other peoples') cars. The problem with such a simple definition is that it covers such a broad class. It covers simple contracts like Futures where the end value just depends on the price of something on a future date. But it extends to contracts complicated enough that people in finance call them Exotics. Derivatives are broadly used for two things reducing risk (sometimes called insurance) and speculation. A farmer can use derivatives to make sure she gets paid a certain amount for her corn. A banker can group a bunch of loans together and sell slices to reduce the pain of a particular loan failing. At the same time people can use the same instruments to speculate on the price of (for example) that corn or those loans and the main advantage is that they don't have to buy the corn or loans directly. Any farmer will tell you corn can be very expensive to store. Derivatives generally cause problems both individually and sometimes world wide when people don't properly understand the risks involved. The most famous example being Mortgage-backed Securities and the recent Great Recession. You can start understand the instruments and their risks by this wonderful Wikipedia article and later perhaps a used collection of CFA books which cover derivatives in great detail. Edit: Michael Grünewald mentioned Hull's text on derivatives a wonderful middle ground between Wikipedia and the CFA books that I can't believe I didn't think about myself.", "title": "" }, { "docid": "115134", "text": "How I understand it is: supply/demand affect price of stock negatively/positively, respectively. Correct. Volume is the amount of buying/selling activity in these stocks (more volume = more fluctuation, right?). Sort of. Higher volume means higher liquidity. That is, a stock that is traded more is easier to trade. It doesn't necessarily mean more fluctuation and in the real world, it often means that these are well-understood stocks with a high amount of analyst coverage. This tends towards these stocks not being as volatile as smaller stocks with less liquidity. Company revenue (and profit) will help an investor predict company growth. That is one factor in a stock price. There are certain stocks that you would buy without them making a profit because their future revenue looks potentially explosive. However, these stocks are very risky and are bubble-prone. If you're starting out in the share market, it's generally a good idea to invest in index funds (I am not a broker, my advice should not be taken as financial advice). These funds aggregate risk by holding a lot of different companies. Also, statistics have shown that over time, buying and holding index funds long term tends to dramatically outperform other investment strategies, particularly for people with low amounts of capital.", "title": "" }, { "docid": "520216", "text": "\"It's interesting that after reading this article you would make an assumption about where the stock market is headed. This article specifically says that the only way to know that is to know where interest rates are going, and for that we can guarantee no one knows. The takeaway is this: \"\"The key to investing is not assessing how much an industry is going to affect society, or how much it will grow, but rather determining the competitive advantage of any given company and, above all, the durability of that advantage. The products or services that have wide, sustainable moats around them are the ones that deliver rewards to investors.\"\" Intelligent investors should have no concern about what \"\"the market\"\" is doing. Analyze businesses, not the stock market.\"", "title": "" }, { "docid": "344175", "text": "The benefit of a dividend reinvestment program is you, generally, don't pay transaction costs or commissions and you don't have to remember to do it. Whether or not you may be able to eek out a little more by managing this yourself is a crapshoot and the equivalent of timing the market. If you're so good at timing the market you shouldn't even be holding the stock, you should be buying and selling as the price fluctuates.", "title": "" }, { "docid": "91032", "text": "Don't go for the 'fast buck'. There's no such thing. There are two types of people that make money on the stock market: Investors and Speculators. Investors are people that pick a stock that's relatively low, relatively secure, and buy the stock for the long run, 5, 10 years or more. Warren Buffet said his ideal period for investing is forever. Basically, a well run company should always be a good investment. Speculators go for the fluctuations in stock prices. Day traders, Options, etc. It's risky business and you'll be able to lose a lot of money in a short term. There's always a risk when you invest your money, so go with MrChrister's advise to start with a simulator. Have fun.", "title": "" }, { "docid": "117082", "text": "\"Someone who buys a stock is fundamentally buying a share of all future dividends, plus the future liquidation value of the company in the event that it is liquidated. While some investors may buy stocks in the hope that they will be able to find other people willing to pay more for the stock than they did, that's a zero sum game. The only way investors can make money in the aggregate is if either stocks pay dividends or if the money paid for company assets at liquidation exceeds total net price for which the company sold shares. One advantage of dividends from a market-rationality perspective is that dividend payments are easy to evaluate than company value. Ideally, the share price of a company should match the present per-share cash value of all future dividends and liquidation, but it's generally impossible to know in advance what that value will be. Stock prices may sometimes rise because of factors which increase the expected per-share cash value of future dividends and liquidations. In a sane market, rising prices on an item will reduce people's eagerness to buy and increase people's eagerness to sell. Unfortunately, in a marketplace where steady price appreciation is expected the feedback mechanisms responsible for stability get reversed. Rapidly rising prices act as a red flag to buyers--unfortunately, bulls don't see red flags as signal to stop, but rather as a signal to charge ahead. For a variety of reasons including the disparate treatment of dividends and capital gains, it's often not practical for a company to try to stabilize stock prices through dividends and stock sales. Nonetheless, dividends are in a sense far more \"\"real\"\" than stock price appreciation, since paying dividends generally requires that companies actually have sources of revenues and profits. By contrast, it's possible for stock prices to go through the roof for companies which have relatively few assets of value and no real expectation of becoming profitable businesses, simply because investors see rising stock prices as a \"\"buy\"\" signal independent of any real worth.\"", "title": "" }, { "docid": "116675", "text": "Dividend yield is a tough thing to track because it's a moving target. Dividends are paid periodically the yield is calculated based on the stock price when the dividend is declared (usually, though some services may update this more frequently). I like to calculate my own dividend by annualizing the dividend payment divided by my cost basis per share. As an example, say you have shares in X, Co. X issues a quarterly dividend of $1 per share and the share price is $100; coincidentally this is the price at which you purchased your shares. But a few years goes by and now X issues it's quarterly dividend of $1.50 per share, and the share price is $160. However your shares only cost you $100. Your annual yield on X is 6%, not the published 3.75%. All of this is to say that looking back on dividend yields is somewhat similar to nailing jello to the wall. Do you look at actual dividends paid through the year divided by share price? Do you look at the annualized dividend at the time of issue then average those? The stock price will fluctuate, that will change the yield; depending on where you bought your stock, your actual yield will vary from the published amount as well.", "title": "" }, { "docid": "173052", "text": "\"Probably the best way to investigate this is to look at an example. First, as the commenters above have already said, the log-return from one period is log(price at time t/price at time t-1) which is approximately equal to the percentage change in the price from time t-1 to time t, provided that this percentage change is not big compared to the size of the price. (Note that you have to use the natural log, ie. log to the base e -- ln button on a calculator -- here.) The main use of the log-return is that is a proxy for the percentage change in the price, which turns out to be mathematically convenient, for various reasons which have mostly already been mentioned in the comments. But you already know this; your actual question is about the average log-return over a period of time. What does this indicate about the stock? The answer is: if the stock price is not changing very much, then the average log-return is about equal to the average percentage change in the price, and is very easy and quick to calculate. But if the stock price is very volatile, then the average log-return can be wildly different to the average percentage change in the price. Here is an example: the closing prices for Pitchfork Oil from last week's trading are: 10, 5, 12, 5, 10, 2, 15. The percentage changes are: -0.5, 1.4, -0.58, 1, -0.8, 6.5 (where -0.5 means -50%, etc.) The average percentage change is 1.17, or 117%. On the other hand, the log-returns for the same period are -0.69, 0.88, -0.88, 0.69, -1.6, 2, and the average log-return is about 0.068. If we used this as a proxy for the average percentage change in the price over the whole seven days, we would get 6.8% instead of 117%, which is wildly wrong. The reason why it is wrong is because the price fluctuated so much. On the other hand, the closing prices for United Marshmallow over the same period are 10, 11, 12, 11, 12, 13, 15. The average percentage change from day to day is 0.073, and the average log-return is 0.068, so in this case the log-return is very close to the percentage change. And it has the advantage of being computable from just the first and last prices, because the properties of logarithms imply that it simplifies to (log(15)-log(10))/6. Notice that this is exactly the same as for Pitchfork Oil. So one reason why you might be interested in the average log-return is that it gives a very quick way to estimate the average return, if the stock price is not changing very much. Another, more subtle reason, is that it actually behaves better than the percentage return. When the price of Pitchfork jumps from 5 to 12 and then crashes back to 5 again, the percentage changes are +140% and -58%, for an average of +82%. That sounds good, but if you had bought it at 5, and then sold it at 5, you would actually have made 0% on your money. The log-returns for the same period do not have this disturbing property, because they do add up to 0%. What's the real difference in this example? Well, if you had bought $1 worth of Pitchfork on Tuesday, when it was 5, and sold it on Wednesday, when it was 12, you would have made a profit of $1.40. If you had then bought another $1 on Wednesday and sold it on Thursday, you would have made a loss of $0.58. Overall, your profit would have been $0.82. This is what the average percentage return is calculating. On the other hand, if you had been a long-term investor who had bought on Tuesday and hung on until Thursday, then quoting an \"\"average return\"\" of 82% is highly misleading, because it in no way corresponds to the return of 0% which you actually got! The moral is that it may be better to look at the log-returns if you are a buy-and-hold type of investor, because log-returns cancel out when prices fluctuate, whereas percentage changes in price do not. But the flip-side of this is that your average log-return over a period of time does not give you much information about what the prices have been doing, since it is just (log(final price) - log(initial price))/number of periods. Since it is so easy to calculate from the initial and final prices themselves, you commonly won't see it in the financial pages, as far as I know. Finally, to answer your question: \"\"Does knowing this single piece of information indicate something about the stock?\"\", I would say: not really. From the point of view of this one indicator, Pitchfork Oil and United Marshmallow look like identical investments, when they are clearly not. Knowing the average log-return is exactly the same as knowing the ratio between the final and initial prices.\"", "title": "" }, { "docid": "484778", "text": "\"There are a few reason why the stock price decreases after a dividend is paid: What's the point of paying a dividend if the stock price automatically decreases? Don't the shareholders just break even? Companies have to do something with their profits. They beholden to their shareholders to make them money either by increasing the share value or paying dividends. So they have the choice between reinvesting their profits into the company to grow the business or just handing the profits directly to the owners of the business (the shareholders). Some companies are as big as they want to be and investing their profits into more capital offers them diminishing returns. These companies are more likely to pay dividends to their shareholders. I assume the price of the stock \"\"naturally\"\" increases over the year to reflect the amount of the dividend payment. This is kind of a vague question but then doesn't it make it difficult to evaluate the fluctuations in stock price (in the way that you would a company that doesn't pay a dividend)? It depends on the company. The price may recover the dividend drop... could take a few days to a week. And that dependings on the company's performance and the overall market performance. With respect to options, I assume nothing special happens? So say I bought $9 call options yesterday that were in the money, all of a sudden they're just not? Is this typically priced into the option price? Is there anything else I need to know about buying options in companies that pay dividends? What if I had an in-the-money option, and all of a sudden out of nowhere a company decides to pay a dividend for the first time. Am I just screwed? One key is that dividends are announced in advance (typically at least, if not always; not sure if it's required by law but I wouldn't be surprised). This is one reason people will sometimes exercise a call option early, because they want to get the actual stock in order to earn the dividend. For \"\"out of the ordinary\"\" large cash dividends (over 10% is the guideline), stock splits, or other situations an option can be adjusted: http://www.888options.com/help/faq/splits.jsp#3 If you have an options account, they probably sent you a \"\"Characteristics and Risks of Standardized Options\"\" booklet. It has a section discussing this topic and the details of what kinds of situations trigger an adjustment. A regular pre-announced <10% dividend does not, while a special large dividend would, is what I roughly get from it. That \"\"Characteristics and Risks of Standardized Options\"\" is worth reading by the way; it's long and complicated, but well, options are complicated. Finally, do all companies reduce their stock price when they pay a dividend? Are they required to? I'm just shocked I've never heard of this before. The company doesn't directly control the stock price, but I do believe this is automatic. I think the market does this automatically because if they didn't, there would be enough people trying to do dividend capture arbitrage that it would ultimately drive down the price.\"", "title": "" } ]
PLAIN-1237	gallbladder disease	[ { "docid": "MED-2205", "text": "AIM: To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. RESULTS: SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r2 = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from 8.2 ± 1.3 g/mice in the control to 6.1 ± 1.4 g/mice in the ip group (P = 0.035). CONCLUSION: SPP exerts significant antiproliferative and antimetastatic effects on human colorectal cancer cell lines, both in vitro and in vivo.", "title": "Anticancer effects of sweet potato protein on human colorectal cancer cells" }, { "docid": "MED-2781", "text": "Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.", "title": "Effect of different curcumin dosages on human gall bladder." }, { "docid": "MED-2788", "text": "Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.", "title": "Clinical utility of curcumin extract." }, { "docid": "MED-2210", "text": "We investigated the effects of sporamin, the major soluble protein with a kunitz-type trypsin inhibitory activity in the root tuber of the sweet potato, on cell proliferation, apoptosis, Akt/GSK-3 signaling and its related genes to provide more insights in the mechanism behind the inhibitory effects of sporamin in a human tongue cancer line Tca8113. In this study, sporamin inhibited cell proliferation and induced apoptosis in Tca8113 cells in a concentration-dependent and time-dependent manner. Consistently, Bax was up-regulated and Bcl-2 was down-regulated in sporamin-treated cells. Furthermore, Akt/GSK-3 signaling was down-regulated in sporamin-treated cells. Consistently, the phosphorylated Bad was significantly declined in sporamin-treated Tca8113 cells. These results suggest the antiproliferative effects of sporamin in Tca8113 cells might result partly from induction of apoptosis by down-regulating Akt/GSK-3 pathway. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.", "title": "Sporamin induce apoptosis in human tongue carcinoma cells by down-regulating Akt/GSK-3 signaling." }, { "docid": "MED-2206", "text": "Sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions. This article presents recipes of products made from sweet potato and determines the consumer acceptability of products containing from 6% to 20% sweet potato on a dry weight basis. These products were developed for use in nutritious and palatable meals for future space explorers. Sensory evaluation (appearance/color, aroma, texture, flavor/taste, and overall acceptability) studies were conducted to determine the consumer acceptability of vegetarian products made with sweet potato using panelists at NASA/Johnson Space Center in Houston, TX. None of these products including the controls, contained any ingredient of animal origin with the exception of sweet potato pie. A 9-point hedonic scale (9 being like extremely and 1 being dislike extremely) was used to evaluate 10 products and compare them to similar commercially available products used as controls. The products tested were pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels. All of the products were either liked moderately or liked slightly with the exception of the sweet potato vegetable patties, which were neither liked nor disliked. Mean comparisons of sensory scores of sweet potato recipes and their controls were accomplished by using the Student t-test. Because of their nutritional adequacy and consumer acceptability, these products are being recommended to NASA's Advanced Life Support Program for inclusion in a vegetarian menu plan designed for lunar/Mars space missions.", "title": "Consumer acceptance of vegetarian sweet potato products intended for space missions." }, { "docid": "MED-2787", "text": "BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.", "title": "The effect of curcumin and placebo on human gall-bladder function: an ultrasound study." }, { "docid": "MED-2777", "text": "BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.", "title": "The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994." }, { "docid": "MED-2201", "text": "Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.", "title": "New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?" }, { "docid": "MED-2810", "text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".", "title": "Curcumin as \"Curecumin\": from kitchen to clinic." }, { "docid": "MED-2204", "text": "The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated \"ipomoein,\" which was reported by Jones and Gersdorff, (1931). Later, \"ipomoein\" was renamed \"sporamin\" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam)." }, { "docid": "MED-2818", "text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.", "title": "Curcumin: the story so far." }, { "docid": "MED-2208", "text": "BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.", "title": "Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer." }, { "docid": "MED-2780", "text": "Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.", "title": "Total and soluble oxalate content of some Indian spices." }, { "docid": "MED-2816", "text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.", "title": "Plant-derived health: the effects of turmeric and curcuminoids." }, { "docid": "MED-2815", "text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin, a component of turmeric: from farm to pharmacy." }, { "docid": "MED-2202", "text": "The overall objective of this chapter is to review the past, present, and future role of the sweet potato (Ipomoea batatas [L.] Lam) in human nutrition. Specifically, the chapter describes the role of the sweet potato in human diets; outlines the biochemical and nutritional composition of the sweet potato with emphasis on its beta-carotene and anthocyanin contents; highlights sweet potato utilization, and its potential as value-added products in human food systems; and demonstrates the potential of the sweet potato in the African context. Early records have indicated that the sweet potato is a staple food source for many indigenous populations in Central and South Americas, Ryukyu Island, Africa, the Caribbean, the Maori people, Hawaiians, and Papua New Guineans. Protein contents of sweet potato leaves and roots range from 4.0% to 27.0% and 1.0% to 9.0%, respectively. The sweet potato could be considered as an excellent novel source of natural health-promoting compounds, such as beta-carotene and anthocyanins, for the functional food market. Also, the high concentration of anthocyanin and beta-carotene in sweet potato, combined with the high stability of the color extract make it a promising and healthier alternative to synthetic coloring agents in food systems. Starch and flour processing from sweet potato can create new economic and employment activities for farmers and rural households, and can add nutritional value to food systems. Repositioning sweet potato production and its potential for value-added products will contribute substantially to utilizing its benefits and many uses in human food systems. Multidisciplinary, integrated research and development activities aimed at improving production, storage, postharvest and processing technologies, and quality of the sweet potato and its potential value-added products are critical issues, which should be addressed globally.", "title": "Sweet potato: a review of its past, present, and future role in human nutrition." }, { "docid": "MED-2209", "text": "This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.", "title": "Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica" }, { "docid": "MED-2782", "text": "BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.", "title": "Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial." }, { "docid": "MED-2200", "text": "Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.", "title": "Diet and gallbladder cancer: a case-control study." }, { "docid": "MED-2783", "text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic." }, { "docid": "MED-2207", "text": "The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.", "title": "Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots." }, { "docid": "MED-2785", "text": "Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.", "title": "Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells." }, { "docid": "MED-2786", "text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.", "title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?" }, { "docid": "MED-2203", "text": "Constipation is a common health problem that adversely affects quality of life and the prognosis of hospitalized patients with acute coronary syndromes (ACS). The purpose of this study was to develop and test the sweet potato/footbath/acupressure massage (SFA) intervention as a safe treatment for prevention of constipation and to increase satisfaction with bowel emptying in hospitalized patients with ACS. The study was a prospective, randomized controlled trial with a sample of 93 patients (SFA group, n = 44; usual care group, n = 49). Patients in the SFA group received SFA intervention combined with usual care. The results showed that there were statistical differences between the two groups in terms of (1) the incidence of constipation; (2) the use of laxatives and enemas; (3) patients' subjective satisfaction with their bowel emptying during hospitalization; and (4) sensation of incomplete evacuation and anorectal obstruction/blockade. The SFA intervention was more effective, economical, and practical than usual care alone in managing constipation and satisfaction with defecation in patients hospitalized with ACS.", "title": "The effect of a sweet potato, footbath, and acupressure intervention in preventing constipation in hospitalized patients with acute coronary syndro..." } ]	[ { "docid": "MED-4838", "text": "With a prevalence of 10-15% in adults in Europe and the USA, gallstones are the most common digestive disease needing admission to hospital in the West. The interplay between interprandial and postprandial physiological responses to endogenous and dietary lipids underscores the importance of coordinated hepatobiliary and gastrointestinal functions to prevent crystallisation and precipitation of excess biliary cholesterol. Indeed, identifying the metabolic and transcriptional pathways that drive the regulation of biliary lipid secretion has been a major achievement in the field. We highlight scientific advances in protein and gene regulation of cholesterol absorption, synthesis, and catabolism, and biliary lipid secretion with respect to the pathogenesis of cholesterol gallstone disease. We discuss the physical-chemical mechanisms of gallstone formation in bile and the active role of the gallbladder and the intestine. We also discuss gaps in our knowledge of the pathogenesis of gallstone formation and the potential for gene targeting in therapy.", "title": "Cholesterol gallstone disease." }, { "docid": "MED-4640", "text": "BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be \"improved\". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.", "title": "PASSCLAIM--gut health and immunity." }, { "docid": "MED-1717", "text": "BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.", "title": "Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies." }, { "docid": "MED-2162", "text": "BACKGROUND: The influence of excess body weight on the risk of death from cancer has not been fully characterized. METHODS: In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. RESULTS: The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. CONCLUSIONS: Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Copyright 2003 Massachusetts Medical Society", "title": "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults." }, { "docid": "MED-983", "text": "BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. METHODS: A stochastic, multistate model was used in conjunction with United Nations worldwide population forecasts and data from epidemiological studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will quadruple, by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care, equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050, with nearly the entire decline attributable to decreases in persons needing a high level of care. CONCLUSIONS: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in the onset and progression of Alzheimer's disease can significantly reduce the global burden of this disease.", "title": "Forecasting the global burden of Alzheimer's disease." }, { "docid": "MED-4431", "text": "BACKGROUND: Workers in poultry plants have high exposure to a variety of transmissible agents present in poultry and their products. Subjects in the general population are also exposed. It is not known whether many of these agents cause disease in humans. If they do, we reason this would be readily evident in a highly exposed group such as poultry workers. We report here on mortality from non-malignant diseases in a cohort of poultry workers. METHODS: Mortality was compared with that of the US general population, and with that of a comparison group from the same union. Risk was estimated by standardized mortality ratio, proportional mortality ratio, and directly standardized risk ratio. RESULTS: Poultry workers as a group had an overall excess of deaths from diabetes, anterior horn disease, and hypertensive disease, and a deficit of deaths from intracerebral hemorrhage. Deaths from zoonotic bacterial diseases, helminthiasis, myasthenia gravis, schizophrenia, other diseases of the spinal cord, diseases of the esophagus and peritonitis were non-significantly elevated overall by all analyses, and significantly so in particular race/sex subgroups. CONCLUSIONS: Poultry workers may have excess occurrence of disease affecting several organs and systems, probably originating from widespread infection with a variety of microorganisms. The results for neurologic diseases could well represent important clues to the etiology of these diseases in humans. The small numbers of deaths involved in some cases limit interpretation.", "title": "Mortality in the Baltimore union poultry cohort: non-malignant diseases." }, { "docid": "MED-5030", "text": "Study Objectives: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. Design: Cohort study. Setting: Community-based study. Participants: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. Interventions: N/A. Measurements and Results: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19–4.50) for coronary heart disease in women, 1.49 (1.02–2.18) and 1.47 (1.01–2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02–1.64) and 1.28 (1.03–1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. Conclusions: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep. Citation: Ikehara S; Iso H; Date C; Kikuchi S; Watanabe Y; Wada Y; Inaba Y; Tamakoshi A. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study. SLEEP 2009;32(3):259–301.", "title": "Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women: the JACC Study" }, { "docid": "MED-975", "text": "Diverticular disease of the colon is a new disease that appeared at the beginning of this century. It is now the commonest disease of the colon in the Western world, being found in 1 in 3 people of over 60 years of age. The pathogenesis of the disease involves excessive segmentation, but this does not explain its aetiology. The historical appearance of the disease on the clinical scene and its geographical distribution suggest that it is due to the removal of fibre from carbohydrates. The author treated 70 patients with symptomatic diverticular disease with a high-fibre diet. The results of this and the effects of bran are discussed.", "title": "Diverticular disease of the colon. The first of the Western diseases shown to be due to a deficiency of dietary fibre." }, { "docid": "MED-3480", "text": "Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968-72. The participants were 40-74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0.75 (95 % CI 0.59, 0.94), 0.73 (95 % CI 0.54, 1.00) and 0.47 (95 % CI 0.24, 0.92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0.79; 95 % CI 0.63, 0.99), ischaemic stroke (RR 0.67; 95 % CI 0.49, 0.92) and intracerebral haemorrhage (RR 0.49; 95 % CI 0.25, 0.98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases.", "title": "Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption." }, { "docid": "MED-5281", "text": "Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.", "title": "The Vascular Endothelium and Human Diseases" }, { "docid": "MED-3706", "text": "Autoimmune diseases are complex diseases resulting of the interaction between both genetics and environmental factors over time. Different phases in the development of autoimmune diseases are characterized by the detection of serum autoantibodies several months or years before the onset of clinical manifestations and subsequent diagnosis. In addition to serum antibodies, genetic susceptibility factors may predict the future development of the disease. Currently, prediction in type 1 diabetes is the most accurate, with the analysis of genetic susceptibility factors in first-degree relatives of patients and several autoantibody tests. In the future, multiple antibodies test, in combination with the analysis of genetics, epigenetics and immunological anomalies in fine models may allow the precise prediction in autoimmune diseases. Prevention measures might thus be introduced as an attempt to avoid or delay the disease. Copyright Â© 2011 Elsevier B.V. All rights reserved.", "title": "Are autoimmune diseases predictable?" }, { "docid": "MED-4345", "text": "BACKGROUND: n-3 (omega-3) Polyunsaturated fatty acids (PUFAs), fish, and nuts can regulate inflammatory processes and responses. OBJECTIVE: We investigated whether dietary intakes of PUFAs [n-3, n-6 (omega-6), and α-linolenic acid], fish, and nuts were associated with 15-y mortality attributed to noncardiovascular, noncancer inflammatory diseases. DESIGN: The analyses involved 2514 participants aged ≥49 y at baseline. Dietary data were collected by using a semiquantitative food-frequency questionnaire, and PUFA, fish, and nut intakes were calculated. Inflammatory disease mortality was confirmed from the Australian National Death Index. RESULTS: Over 15 y, 214 subjects died of inflammatory diseases. Women in the highest tertiles of total n-3 PUFA intake, compared with those in the lowest tertile of intake at baseline, had a 44% reduced risk of inflammatory disease mortality (P for trend = 0.03). This association was not observed in men. In both men and women, each 1-SD increase in energy-adjusted intake of α-linolenic acid was inversely associated with inflammatory mortality (hazard ratio: 0.83; 95% CI: 0.71, 0.98). Subjects in the second and third tertiles of nut consumption had a 51% and 32% reduced risk of inflammatory disease mortality, respectively, compared with those in the first tertile (reference). Dietary intakes of long-chain n-3 and n-6 PUFAs and fish were not associated with inflammatory disease mortality. CONCLUSIONS: We report on a novel link between dietary intake of total n-3 PUFA and risk of inflammatory disease mortality in older women. Furthermore, our data indicate a protective role of nuts, but not fish, against inflammatory disease mortality.", "title": "Consumption of polyunsaturated fatty acids, fish, and nuts and risk of inflammatory disease mortality." }, { "docid": "MED-1167", "text": "Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Pesticides and human chronic diseases: evidences, mechanisms, and perspectives." }, { "docid": "MED-4013", "text": "OBJECTIVE: The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown. METHODS AND RESULTS: We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03). CONCLUSIONS: Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation, possibly placing them at increased risk for cardiovascular disease.", "title": "Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation." }, { "docid": "MED-4496", "text": "BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.", "title": "The effect of fruit and vegetable intake on risk for coronary heart disease." }, { "docid": "MED-4173", "text": "OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.", "title": "Chronic disease and infant nutrition: is it significant to public health?" }, { "docid": "MED-3938", "text": "Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.", "title": "Association between polychlorinated biphenyls and Parkinson’s disease neuropathology" }, { "docid": "MED-970", "text": "Objective To examine the associations of a vegetarian diet and dietary fibre intake with risk of diverticular disease. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort of mainly health conscious participants recruited from around the United Kingdom. Participants 47 033 men and women living in England or Scotland of whom 15 459 (33%) reported consuming a vegetarian diet. Main outcome measures Diet group was assessed at baseline; intake of dietary fibre was estimated from a 130 item validated food frequency questionnaire. Cases of diverticular disease were identified through linkage with hospital records and death certificates. Hazard ratios and 95% confidence intervals for the risk of diverticular disease by diet group and fifths of intake of dietary fibre were estimated with multivariate Cox proportional hazards regression models. Results After a mean follow-up time of 11.6 years, there were 812 cases of diverticular disease (806 admissions to hospital and six deaths). After adjustment for confounding variables, vegetarians had a 31% lower risk (relative risk 0.69, 95% confidence interval 0.55 to 0.86) of diverticular disease compared with meat eaters. The cumulative probability of admission to hospital or death from diverticular disease between the ages of 50 and 70 for meat eaters was 4.4% compared with 3.0% for vegetarians. There was also an inverse association with dietary fibre intake; participants in the highest fifth (≥25.5 g/day for women and ≥26.1 g/day for men) had a 41% lower risk (0.59, 0.46 to 0.78; P<0.001 trend) compared with those in the lowest fifth (<14 g/day for both women and men). After mutual adjustment, both a vegetarian diet and a higher intake of fibre were significantly associated with a lower risk of diverticular disease. Conclusions Consuming a vegetarian diet and a high intake of dietary fibre were both associated with a lower risk of admission to hospital or death from diverticular disease.", "title": "Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study of British vegetarians and non-vegetarians" }, { "docid": "MED-5293", "text": "Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.", "title": "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010" }, { "docid": "MED-2385", "text": "The purpose of this investigation was to estimate the total hair mercury of diseased people (not including patients of mercury poisoning such as Minamata disease). Hair samples were collected from 133 diseased volunteers in Tokyo and the surrounding areas from Oct. 1992 to June 1993. The total mercury concentrations in the hair of ordinary diseased people (atopic dermatitis, asthma, dementia, cerebral infarct, osteoporosis, hypertension and diabetes) were from 2.08 ppm to 36.5 ppm. Those values were considerably higher than that of healthy people of the same age groups. However, the uptake routes and the metabolic mechanism of high hair mercury concentrations in diseased people are not clear.", "title": "Concentration of mercury in hair of diseased people in Japan." }, { "docid": "MED-5303", "text": "IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.", "title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors." }, { "docid": "MED-1948", "text": "Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases.", "title": "Curcumin and neurodegenerative diseases" }, { "docid": "MED-2082", "text": "BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..." }, { "docid": "MED-2590", "text": "Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.", "title": "Reversing heart disease in the new millennium--the Fleming unified theory." }, { "docid": "MED-4919", "text": "OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.", "title": "Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study." }, { "docid": "MED-2658", "text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.", "title": "Alkylphenols--potential modulators of the allergic response." }, { "docid": "MED-2924", "text": "Recent advances have been made in our scientific understanding of how berries promote human health and prevent chronic illnesses such as some cancers, heart disease, and neurodegenerative diseases. Cancer is rapidly overtaking heart disease as the number one killer disease in developed countries, and this phenomenon is coupled with a growing aging population and concomitant age-related diseases. Therefore, it is not surprising that consumers are turning toward foods with medicinal properties as promising dietary interventions for disease prevention and health maintenance. Among fruits, berries of all colors have emerged as champions with substantial research data supporting their abilities to positively affect multiple disease states. Apart from several essential dietary components found in berries, such as vitamins, minerals, and fiber, berries also contain numerous bioactives that provide health benefits that extend beyond basic nutrition. Berry bioactives encompass a wide diversity of phytochemicals (phytonutrients) ranging from fat-soluble/lipophilic to water-soluble/hydrophilic compounds. Recent research from laboratories across the globe has provided useful insights into the biological effects and underlying mechanisms of actions resulting from eating berries. The cluster of papers included here represents a cross section of topics discussed at the 2009 International Berry Health Benefits Symposium. Together, these papers provide valuable insight into recent research trends and advances made into evaluating the various health benefits that may result from the consumption of berries and their derived products.", "title": "Recent trends and advances in berry health benefits research." }, { "docid": "MED-3966", "text": "Crohn's disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0.1-1.0 microm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn's disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 10(12) particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn's disease, with a significant (P= 0.002) improvement in the Crohn's disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.", "title": "Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease." }, { "docid": "MED-5018", "text": "Purpose of review This article reviews the AAP’s statement on early nutritional interventions on the development of atopic disease in infants and children. Recent findings Recent findings suggest that restriction of maternal diet during pregnancy and lactation does not play a major role in the development of allergic disease. In high risk infants exclusive breastfeeding for at least 4 months prevents or delays atopic dermatitis, cow milk allergy, and wheezing early in life. There is evidence that supplementing breastfeeding with a hydrolyzed formula protects against atopic disease, especially atopic dermatitis in at risk infants. Finally there is little evidence that delaying the introduction of complimentary foods beyond 4 to 6 months of age has any protective effect against allergy. There is insufficient data that any dietary intervention beyond 4 to 6 months of age has any protective effect against developing atopic disease. Summary In high risk infants there is evidence for exclusive breastfeeding for at least 4 months and delaying of complimentary foods until 4 to 6 months prevents the development of allergy. There is some evidence that supplementing hydrolyzed formulas in high risk infants may delay or prevent allergic disease. There is no convincing evidence that maternal manipulation of diet during pregnancy or lactation, use of soy products, or infant dietary restrictions beyond 4 to 6 months has any effect on the development of atopic disease.", "title": "American Academy of Pediatrics recommendations on the Effects of Early Nutritional Interventions on the Development of Atopic Disease" }, { "docid": "MED-3387", "text": "Respiratory exposure to diacetyl and diacetyl-containing flavorings used in butter-flavored microwave popcorn (BFMP) causes lung disease, including bronchiolitis obliterans (BO), in flavorings and popcorn manufacturing workers. However, there are no published reports of lung disease among BFMP consumers. We present a case series of three BFMP consumers with biopsy-confirmed BO. We review data relating to consumer exposures, estimate case exposures, and compare them to diacetyl-containing flavoring-exposed manufacturing workers with lung disease. These consumer cases' exposure levels are comparable to those that caused disease in workers. We were unable to identify any other exposures or diseases known or suspected to cause BO in these cases. BFMP poses a significant respiratory risk to consumers. Some manufacturers have substituted diacetyl with other alpha-diketones that are likely to pose a similar risk. Simple consumer practices such as cooling the popcorn bag would eliminate the risk of severe lung disease.", "title": "Bronchiolitis obliterans and consumer exposure to butter-flavored microwave popcorn: a case series." } ]
5ae730b8554299572ea54777	George Nolfi directed what science fiction thriller film that was produced by Chris Moore and stars Matt Damon and who?	[ { "docid": "23778776", "text": "The Adjustment Bureau is a 2011 American science fiction thriller film loosely based on the Philip K. Dick short story, \"Adjustment Team\". The film was written and directed by George Nolfi, produced by Chris Moore and stars Matt Damon and Emily Blunt. The cast also includes Anthony Mackie, John Slattery, Michael Kelly, and Terence Stamp. The film tells the story of a young man who discovers that what appear to be chance events in his life are controlled by a technologically advanced intelligence network. After an event not planned by these controllers occurs – a romantic encounter with a young dancer – he struggles against their manipulation despite their promise of a great future for him.", "title": "" }, { "docid": "2830674", "text": "George Nolfi is an American screenwriter, producer and director. He directed the 2011 film \"The Adjustment Bureau\", which he also wrote (adapted from a short story by Philip K. Dick).", "title": "" } ]	[ { "docid": "21382197", "text": "James Cameron is a Canadian director, screenwriter, and producer who has had an extensive career in film and television. Cameron's debut was the 1978 science fiction short \"Xenogenesis\", which he directed, wrote and produced. In the early part of his career, he did various technical jobs such as special visual effects producer, set dresser assistant, matte artist, and photographer. His feature directorial debut was the 1981 release \"\". The next film he directed was the science fiction action thriller \"The Terminator\" (1984). It starred Arnold Schwarzenegger as the titular cyborg assassin, and was Cameron's breakthrough feature. In 1986, he directed and wrote the science fiction action sequel \"Aliens\" starring Sigourney Weaver. He followed this by directing another science fiction film \"The Abyss\" (1989). In 1991, Cameron directed the sequel to \"The Terminator\", \"\" (with Schwarzenegger reprising his role), and also executive produced the action crime film \"Point Break\". Three years later he directed a third Schwarzenegger-starring action film \"True Lies\" (1994).", "title": "" }, { "docid": "5804128", "text": "The Power is a 1968 American science fiction thriller film from MGM, produced by George Pal, directed by Byron Haskin (his final film), that stars George Hamilton and Suzanne Pleshette. It is based on the science fiction novel \"The Power\" by Frank M. Robinson.", "title": "" }, { "docid": "2392280", "text": "Syriana is a 2005 American geopolitical thriller film written and directed by Stephen Gaghan, and executive produced by George Clooney, who also stars in the film with an ensemble cast. Gaghan's screenplay is loosely adapted from Robert Baer's memoir \"See No Evil\". The film focuses on petroleum politics and the global influence of the oil industry, whose political, economic, legal, and social effects are experienced by a Central Intelligence Agency operative (George Clooney), an energy analyst (Matt Damon), a Washington, D.C. attorney (Jeffrey Wright), and a young unemployed Pakistani migrant worker (Mazhar Munir) in an Arab state in the Persian Gulf. The film also features an extensive supporting cast including Amanda Peet, Tim Blake Nelson, Mark Strong, Alexander Siddig, Amr Waked, and Academy Award winners Christopher Plummer, Chris Cooper and William Hurt.", "title": "" }, { "docid": "43539350", "text": "Spectral is an American military science fiction film directed by Nic Mathieu. The screenplay was written by Ian Fried, Nic Mathieu and George Nolfi from a screen story by Fried. The film stars James Badge Dale, Max Martini, Emily Mortimer, and Bruce Greenwood. The film was released on December 9, 2016 on Netflix.", "title": "" }, { "docid": "44055263", "text": "\"Star Trek\" is a 2009 American science fiction film produced by Spyglass Entertainment and Bad Robot Productions, and was distributed by Paramount Pictures. It was written by Roberto Orci and Alex Kurtzman; the producers of the film were Damon Lindelof and J. J. Abrams, the latter of which also directed the film. It is the eleventh film in the \"Star Trek\" film franchise and is also a reboot that features the main characters of the , portrayed by a new cast. The film follows James T. Kirk (Chris Pine) and Spock (Zachary Quinto) aboard the USS \"Enterprise\" as they combat a Romulan from the future who threatens the United Federation of Planets as he seeks his revenge.", "title": "" }, { "docid": "53258014", "text": "Lauren Beck is an American film producer. Best known for producing critically acclaimed film \"Manchester by the Sea\" (2016) that earned her Academy Award for Best Picture nomination with Matt Damon, Kimberly Steward, Chris Moore, and Kevin J. Walsh.", "title": "" }, { "docid": "30294906", "text": "Gravity is a 2013 science fiction thriller film directed, co-written, co-edited and co-produced by Alfonso Cuarón. It stars Sandra Bullock and George Clooney as astronauts who are stranded in space after the mid-orbit destruction of their space shuttle, and their subsequent attempt to return to Earth.", "title": "" }, { "docid": "1854000", "text": "The Bourne Ultimatum is a 2007 American-German action spy thriller film directed by Paul Greengrass loosely based on the novel of the same name by Robert Ludlum. The screenplay was written by Tony Gilroy, Scott Z. Burns and George Nolfi and based on a screen story of the novel by Gilroy. \"The Bourne Ultimatum\" is the third in the \"Jason Bourne\" film series, being preceded by \"The Bourne Identity\" (2002) and \"The Bourne Supremacy\" (2004). The fourth film, \"The Bourne Legacy\", was released in August 2012, without the involvement of Damon, and the fifth film (a direct sequel to \"Ultimatum\"), \"Jason Bourne\", was released in July 2016.", "title": "" }, { "docid": "53258036", "text": "Kevin J. Walsh is an American film producer. He is best known for producing critically acclaimed film \"Manchester by the Sea\" (2016) through his production company, B Story, in which he earned an Academy Award for Best Picture nomination with Matt Damon, Kimberly Steward, Chris Moore, and Lauren Beck.", "title": "" }, { "docid": "49740268", "text": "Downsizing is a 2017 American science fiction comedy-drama film directed by Alexander Payne and written by Payne and Jim Taylor. The film stars Matt Damon, Christoph Waltz, Hong Chau, Jason Sudeikis, and Kristen Wiig. Principal photography on the film began in Ontario, Canada on April 1, 2016.", "title": "" }, { "docid": "98991", "text": "Dogma is a 1999 American fantasy comedy film, written and directed by Kevin Smith, who also stars along with Ben Affleck, Matt Damon, Linda Fiorentino, Alan Rickman, Bud Cort, Salma Hayek, Chris Rock, Jason Lee, George Carlin, Janeane Garofalo, Alanis Morissette, and Jason Mewes. It is the fourth film in Smith's View Askewniverse series. Brian O'Halloran and Jeff Anderson, stars of the first Askewniverse film \"Clerks\", appear in the film, as do Smith regulars Scott Mosier, Dwight Ewell, Walt Flanagan, and Bryan Johnson.", "title": "" }, { "docid": "27658890", "text": "The Darkest Hour is a 2011 science fiction thriller film directed by Chris Gorak and produced by Timur Bekmambetov. It depicts an alien invasion. The film stars Emile Hirsch, Max Minghella, Olivia Thirlby, Joel Kinnaman and Rachael Taylor, as a group of people caught in the invasion. The film was released on December 25, 2011 in the United States.", "title": "" }, { "docid": "41649549", "text": "A Boy and His Dog is a 1975 American science fiction comedy-drama thriller film produced, written (with Alvy Moore), and directed by L. Q. Jones, starring Don Johnson, Susanne Benton, Alvy Moore, and Jason Robards. The film was distributed in the United States by LQ/JAF Productions and in the United Kingdom by Anglo-EMI Film Distributors. The film's script is based on the 1969 cycle of narratives by fantasy author Harlan Ellison titled \"A Boy and His Dog\".", "title": "" }, { "docid": "48775124", "text": "Suburbicon is a 2017 American crime comedy film directed by George Clooney and written by Joel Coen, Ethan Coen, Clooney and Grant Heslov. The film stars Matt Damon, Julianne Moore and Oscar Isaac. It was screened in the main competition section of the 74th Venice International Film Festival and premiered on September 2, 2017. It was also screened at the 2017 Toronto International Film Festival, and is scheduled to be released in the United States on October 27, 2017.", "title": "" }, { "docid": "39693535", "text": "Firehead is a 1991 science fiction–thriller film. It was directed by Peter Yuval for Action International Pictures, and stars Chris Lemmon and Christopher Plummer. It was filmed in Mobile, Alabama and released theatrically in 1991.", "title": "" }, { "docid": "45229787", "text": "\"Argo\" is a 2012 political thriller directed by Ben Affleck, and produced by Grant Heslov, Affleck and George Clooney. The screenplay by Chris Terrio was adapted from sections of the Central Intelligence Agency (CIA) operative Tony Mendez's memoir \"The Master of Disguise: My Secret Life in the CIA\", and the 2007 \"Wired\" article \"The Great Escape\" by Joshuah Bearman on the Canadian Caper. The film stars Affleck as Mendez, who attempts to rescue six United States diplomats from Tehran, Iran, during the 1979–81 Iran hostage crisis by pretending that they are part of a film crew scouting the country for the filming of a fictitious science-fiction film, \"Argo\". Bryan Cranston, Alan Arkin, and John Goodman feature in supporting roles.", "title": "" }, { "docid": "43683268", "text": "The Martian is a 2015 science fiction film directed by Ridley Scott and based on Andy Weir's 2011 novel of the same name. Matt Damon stars as an astronaut who is mistakenly presumed dead and left behind on Mars. The film depicts his struggle to survive and others' efforts to rescue him. The film's ensemble cast also features Jessica Chastain, Kristen Wiig, Jeff Daniels, Michael Peña, Kate Mara, Sean Bean, Sebastian Stan, Donald Glover, Aksel Hennie and Chiwetel Ejiofor.", "title": "" }, { "docid": "34541698", "text": "Riddick is a 2013 American science fiction thriller film, the third installment in the \"Riddick\" film series. Produced by and starring Vin Diesel as the title character, \"Riddick\" is written and directed by David Twohy, who previously wrote and directed the first two installments, \"Pitch Black\" (2000) and \"The Chronicles of Riddick\" (2004).", "title": "" }, { "docid": "8425973", "text": "Slipstream is a 1989 science fiction film directed by Steven Lisberger, who had previously directed the cult classic 1982 science fiction film \"Tron\". It was produced by Gary Kurtz, best known for his collaboration with George Lucas on the first two \"Star Wars\" films and \"American Graffiti\". \"Slipstream\" reunited Kurtz with his \"Star Wars\" lead Mark Hamill, who features alongside Bill Paxton, Bob Peck and Kitty Aldridge, with cameo appearances from Robbie Coltrane, Ben Kingsley and F. Murray Abraham.", "title": "" }, { "docid": "10308922", "text": "Syriana is the original soundtrack, on the RCA Victor label, of the 2005 Academy Award- and Golden Globe-winning film \"Syriana\" starring Kayvan Novak, Matt Damon, George Clooney (who won the Academy Award for Best Supporting Actor for his role as \"Bob Barnes\" in this film), Christopher Plummer, Jeffrey Wright and Chris Cooper. The original score and songs were composed by Alexandre Desplat.", "title": "" }, { "docid": "41420464", "text": "\"Gravity\" is a 2013 3D science-fiction thriller film directed, co-produced, co-written, and co-edited by Alfonso Cuarón. The film's musical score was composed by Steven Price, with the cinematography provided by Cuarón's longtime collaborator, Emmanuel Lubezki. The film stars Sandra Bullock and George Clooney as astronauts involved in the mid-orbit destruction of a space shuttle and their attempt to return to Earth.", "title": "" }, { "docid": "706038", "text": "Project Greenlight was an American documentary television series focusing on first-time filmmakers being given the chance to direct a feature film. It was created by Alex Keledjian, developed by Eli Holzman and produced by Ben Affleck, Matt Damon, Sean Bailey, and Chris Moore through their production company LivePlanet, along with Miramax Films. \"Project Greenlight\" first aired on HBO for two seasons (aired 2001–03) before moving to Bravo for season three in 2005. The series returned in 2015 for a fourth season airing on HBO. On July 26, 2016, the show was cancelled.", "title": "" }, { "docid": "53762306", "text": "The Miracle of Manhattan is a lost 1921 American silent melodrama film directed by George Archainbaud and starring Elaine Hammerstein and Matt Moore. It was produced by Lewis J. Selznick(of Selznick Pictures) and released through Select Pictures.", "title": "" }, { "docid": "47404924", "text": "What Happened to Monday (known as Seven Sisters in France) is a dystopian science fiction thriller film, written by Max Botkin and Kerry Williamson, directed by Tommy Wirkola and starring Noomi Rapace, Glenn Close, and Willem Dafoe. Netflix bought the streaming rights to the film for the United States and other markets. Netflix released the film on August 18, 2017.", "title": "" }, { "docid": "13237979", "text": "Push is a 2009 American science fiction action-thriller film directed by Paul McGuigan and written by David Bourla. Starring Chris Evans, Dakota Fanning, Camilla Belle, and Djimon Hounsou. The film centers on a group of people born with various superhuman abilities who band together in order to take down a government agency that is using a dangerous drug to enhance their powers in hopes of creating an army of super soldiers.", "title": "" }, { "docid": "2530593", "text": "Anthony Joseph Gilroy (born September 11, 1956) is an American screenwriter and filmmaker. He wrote the screenplays for the first four films of the \"Bourne\" series starring Matt Damon, among other successful films, and directed the fourth film of the franchise. He was nominated for Academy Awards for his direction and script for \"Michael Clayton\", starring George Clooney. Gilroy wrote and directed \"Duplicity\", starring Julia Roberts and Clive Owen, and co-wrote \"Rogue One: A Star Wars Story\".", "title": "" }, { "docid": "1964091", "text": "Next is a 2007 American science fiction action thriller film directed by Lee Tamahori and starring Nicolas Cage, Julianne Moore, Jessica Biel, Thomas Kretschmann, Tory Kittles, and Peter Falk. The film's original script was loosely based on the science fiction short story \"The Golden Man\" by Philip K. Dick. The film tells the story of Cris Johnson, a small-time magician based in Las Vegas, who has limited clairvoyance; his ability allows him to see into the very immediate future. His gift makes him a target not only of a highly motivated and heavily armed group of terrorists, but also wanted by the FBI to help them fight them.", "title": "" }, { "docid": "536009", "text": "The Talented Mr. Ripley is a 1999 American psychological thriller film written for the screen and directed by Anthony Minghella. An adaptation of Patricia Highsmith's 1955 novel of the same name, the film stars Matt Damon as Tom Ripley, Jude Law as Dickie Greenleaf, Gwyneth Paltrow as Marge Sherwood and Cate Blanchett as Meredith Logue.", "title": "" }, { "docid": "47584944", "text": "The Devil Within (also known as The Devil Within: Rise of Evil) is a 2010 independent feature film starring Grey Damon and Bill Oberst Jr. It was directed by Tom Hardy and written by Matt Dean. The film is a teen thriller set in Hollywood at a girl's 18th birthday party. The film received decent reviews from fans and the horror community.", "title": "" }, { "docid": "1688592", "text": "Brad Anderson (born 1964) is an American film director, producer and writer. A director of thriller and horror films and television projects, he is best known for having directed \"The Machinist\" (2004), starring Christian Bale, and \"The Call\" (2013), starring Halle Berry. He also produced and directed several installments of the FOX science fiction television series \"Fringe\".", "title": "" } ]
4707	Legal Financing	[ { "docid": "521967", "text": "Find a lawyer or law firm who wants to represent you and talk to them.", "title": "" } ]	[ { "docid": "13718", "text": "There are two Questions: Financial institutions do not care about your nationality, only your ability to pay over time. For long term debt the lender will want assurances that the borrower has the ability and means to pay the debt over time. A legal resident in the US should have no more difficulty obtaining financing than a citizen under similar life circumstances. The Lender is also under legal obligation to confirm that the borrower is who they say they are, will have the ability to pay over time AND have no malicious intent in the purchase. Persons who do not have legal status in the US, AND who do not have the means to pay for property outright will have difficulty obtaining financing as they will have trouble establishing the requirements of the Lender. This is simple math, a lender will be reluctant to lend to any person who is more likely to have difficulty paying the obligation than another. In your case Your father would be an unlikely candidate for a mortgage because he cannot establish his legal status nor can he guarantee that he will have the legal right to earn a means to pay the loan back. This puts the lender at risk both of losing the money lent AND losing the right to repossess the property if the borrower doesn't pay. Despite all of the obstacles I have indicated above, it is still possible for your father to purchase property legally, but the risk and the cost go way up for him as a borrower. There may be sellers willing to finance property over time, but your father's status puts him at a disadvantage if the seller is not honest. There may be community coalitions which can help you work through the challenges of property ownership. Please see these related articles", "title": "" }, { "docid": "291526", "text": "As long as you don't finance and the payment is upfront, its up to you and your customer how to pay. If you provide the product before the payment is being made or finance in any way (i.e.: there's debt), then the Canadian dollar, being legal tender in Canada, must be accepted. Considering the large amount, you would probably not be accepting cash anyway, so the point is moot. How they pay their credit cards is not your problem. However, do take into the account the currency exchange rates and fees that add costs to purchasing your product. If you don't have any physical presence (i.e.: online store only, no physical location on Canadian soil), then it goes by the rules of the jurisdiction where you've incorporated. Check with the local legal professional to be sure.", "title": "" }, { "docid": "597229", "text": "While r/finance has some great advice and posters who are well versed in their fields, this appears to be a legal question and if you're really concerned about the legality, I would strongly advise you to check in with a lawyer, not an online internet commenter. While there is a lot of good content on this site, you do see comments where the person is completely talking out of their ass. It would suck for you to raise concerns at your job, based on faulty 'legal' advice.", "title": "" }, { "docid": "485195", "text": "Since your credit score is much better than hers, you should apply for the credit card yourself alone to get the best chance of approval for your card of choice. Once you have the card, you can add her as an authorized user, which will get her a card of her own, tied to your account. Most banks will begin reporting to both of your credit reports, which should help her credit score over time. Keep in mind that you are solely legally responsible for the debt; your girlfriend will be able to make charges and will have no legal responsibility for the debt. Make sure you are comfortable with that. For what it is worth, in general, I recommend against combining your finances with someone who you are not married to, but it seems that you have already done that, so adding a shared credit card to your finances shouldn't be any worse than what you are already doing.", "title": "" }, { "docid": "294621", "text": "This is correct. The most rapidly expanding areas in finance resemble computer science more than they resemble traditional finance. The compliance and legal side of things, however, is only getting more and more complicated. At my firm, the compliance personnel outnumber the traders three to one.", "title": "" }, { "docid": "227910", "text": "For providing financing assistance to the clients, Invoice Finance and Factoring Services are provided by some recognized professional financial services providers in London. They can help in improving cash flows and credit control. Before applying for loans, a business has to undergo the lengthy processes and legal formalities. To simplify these procedures, Forfaiting Financial Services in London are provided to many organizations.", "title": "" }, { "docid": "453263", "text": "Is your name on the title at all? You may have (slightly) more leverage in that case, but co-signing any loans is not a good idea, even for a friend or relative. As this article notes: Generally, co-signing refers to financing, not ownership. If the primary accountholder fails to make payments on the loan or the retail installment sales contract (a type of auto financing dealers sell), the co-signer is responsible for those payments, or their credit will suffer. Even if the co-signer makes the payments, they’re still not the owner if their name isn’t on the title. The Consumer Finance Protection Bureau (CFPB) notes: If you co-sign a loan, you are legally obligated to repay the loan in full. Co-signing a loan does not mean serving as a character reference for someone else. When you co-sign, you promise to pay the loan yourself. It means that you risk having to repay any missed payments immediately. If the borrower defaults on the loan, the creditor can use the same collection methods against you that can be used against the borrower such as demanding that you repay the entire loan yourself, suing you, and garnishing your wages or bank accounts after a judgment. Your credit score(s) may be impacted by any late payments or defaults. Co-signing an auto loan does not mean you have any right to the vehicle, it just means that you have agreed to become obligated to repay the amount of the loan. So make sure you can afford to pay this debt if the borrower cannot. Per this article and this loan.com article, options to remove your name from co-signing include: If you're name isn't on the title, you'll have to convince your ex-boyfriend and the bank to have you removed as the co-signer, but from your brief description above, it doesn't seem that your ex is going to be cooperative. Unfortunately, as the co-signer and guarantor of the loan, you're legally responsible for making the payments if he doesn't. Not making the payments could ruin your credit as well. One final option to consider is bankruptcy. Bankruptcy is a drastic option, and you'll have to weigh whether the disruption to your credit and financial life will be worth it versus repaying the balance of that auto loan. Per this post: Another not so pretty option is bankruptcy. This is an extreme route, and in some instances may not even guarantee a name-removal from the loan. Your best bet is to contact a lawyer or other source of legal help to review your options on how to proceed with this issue.", "title": "" }, { "docid": "208051", "text": "Shanghai can not be the international financial center of China, or China's inbound/outbound trade, as long as it does not have rule of law. Even Chinese corporates go to Hong Kong to sign contracts because the commercial legal system is efficient, fair, and predictable. Shanghai is a city (and a great one, no doubt!) doing business in a restricted, capital-controlled currency, under a legal system which is corrupt and arbitrary. You wouldn't want to get into a dispute there with, say, Bank of China. When there is a trusted legal system in China then finance will follow. Meanwhile, show me anyone who wants to sign an ISDA agreement under Chinese law, subject an international bond indenture to Chinese law (rather than New York or English law), or do a securitization using Chinese law or counterparties. HK's biggest problem may be that the Mainland is imperiling rule of law in the SAR. If that is lost, the city has no reason to exist.", "title": "" }, { "docid": "327544", "text": "Until they're old enough to be legally responsible for their own credit, the only thing you can really do is show them by example how to manage money and credit in your own finances. Teach them budgeting, immerse them in understanding how credit and financing work, and teach them smart ways to make their money work for them. When they're teenagers, you could potentially approach small banks or credit unions about ways to perhaps co-sign loans for them and let them make payments to learn good habits for managing their responsibilities, but that's not always easy either. It won't do anything for their credit, but having the responsibility of coming in to make payments might instill good habits and help their self-esteem at the same time. You have great intentions, but as has been pointed out here already, from a legal standpoint there's not much you can do. All you can do is prepare them for the day when they are on their own and can enter into credit agreements. Kids going to college get into real trouble with credit because cards are handed out like candy to them by the banks, so teaching them money management skills is invaluable and something you can do now.", "title": "" }, { "docid": "547932", "text": "\"To supplement @littleadv's answer, I discovered that our friends at both Skeptics Stack Exchange and Politics Stack Exchange have also addressed this question — at least a few times that I could find. Please refer to: Skeptics SE: Was the 16th Amendment (income tax) improperly ratified? ... with an accepted answer posted by Money's own @DJClayworth. Skeptics SE: Has income tax been found unconstitutional by a court? ... which also mentions the useful IRS page The Truth About Frivolous Tax Arguments. I also highlight the mention to this valuable FAQ mentioned by @Paul, who also participates here at Money, in a comment on the accepted answer: For more information on bad legal arguments, see Tax Protester Legal FAQ – Paul Jan 7 '14 at 6:29 Politics SE: Constitutionality of the Income Tax. I'll add that Money SE is best suited for practical questions relating to an individual's personal finances. While \"\"find ways to [...], minimize taxes, [...]\"\" is specifically mentioned as on-topic, a key word there is \"\"minimize\"\", not \"\"evade\"\". While questions here can overlap with legal or political issues, the focus at Money SE remains on the practical.\"", "title": "" }, { "docid": "195372", "text": "\"Someone asked this over in /r/darknetmarkets , they were asking how to profit off NV specifically, but here's what I wrote there, I'd be curious what you guys think: > Go back in time about 6 mo, case the medical scene for movers and shakers, write some proposals to help them expand. Traditional banks won't touch financing these guys with a 10ft stick right now, the Fed has told them straight up they will lose FDIC membership if they touch \"\"drug money\"\" (cough cough tobacco and alcohol don't count? cough cough). If you don't have a time machine, either come up with a way to be a bank to these guys without going to a Fed lockup, or go finance expansion in the next state which legalizes. It's gonna be a while until these guys get integrated with the regular money system to the point they have stocks and such. Or maybe the Fed freezing them out as they make a fortune will just push forward crypto currency and hasten the collapse of the current money oligarchy, who knows. There was also some comments about shipping from NV to home states, which is probably a bad idea for many reasons. I did however feel I can offer some insight on a legal president for this kind of behavior, but exactly how legal reshipping to avoid direct shipping of a purchase to a state is (I mean, once it's your proper legal property and you're just shipping it to yourself that does seem legal, right?) or if it would get the same blind eye when done with pot are huge unknowns: >I'm sure the Feds will not see a problem with sending drugs to yourself across state lines! Actually funny enough I live in the wine region of CA and there is a whole business here of wine \"\"storage and shipping\"\" places. It's up to the states to decide how or if they allow alcohol to be shipped into their state from others, and a bunch of state have very complex rules or just don't allow it. So if you come out here for tourism, drink some wine at a winery, like it, and ask if you can have some shipped home, the answer is about 50/50 to be 'no'. And if you're a average income pleb, that's your answer. If you're some rich dude however, you can say \"\"ah gotcha, pesky laws... well here's the address of my storage and shipping place, send the 2 cases there then\"\", nobody bats an eye, and off the cases go. Guy goes home, calls up the shipping place, and says \"\"hey pull those cases, my personal property, and ship them to me\"\" and, somehow, magically, this is now legal. I have no idea who's taking on the liability here, if the shipping place has them sign off \"\"we will ship wherever you ask, it's not our job to verify the legality of your request\"\" then I guess it's on the consumer, but if you have an entire business built around circumventing state law it would seem to me that this should be a legal problem. But, wine is a high-end commodity, rich people make their own rules, and if CA turns a blind eye to this practice they get to collect the sales tax as it's sold in CA and shipped to a location in CA, whereas fighting it would hurt their tourism and also send the tax income to the states being shipped to. C.R.E.A.M. baby! Re-reading this now I'm not even sure if there IS a liability here. They bought the property in CA, paid tax in CA, and had it sent to a mailing address in CA. What they do after that with their personal property is not the states business, right? I'd imagine this would be drastically different if shipping for resale. Similarly, I think this all only works if you complete the transaction while physically in the state. So at most this might turn on some weed tourism. The big difference in all of this is that the Fed is fine with alcohol, but not weed, so, while I suspect someone will form such a weed storage and shipping place at some point, I don't really want to be first in line to see how this flys and if it lands you in trouble with the Fed.\"", "title": "" }, { "docid": "109025", "text": "\"It sounds like you are describing \"\"seller-financed\"\" mortgages (also sometimes called \"\"self-financed\"\", where \"\"self\"\" is the seller). In essence the buyer and seller enter into a legal contract (a promissory note) that specifies the payment schedule, interest rate, etc. The nature of the agreement is similar to the kind of mortgage agreement you'd get from the bank, but no bank is involved; it's just an agreeement directly between the buyer and seller. If you search for \"\"seller-financed mortgage\"\" or \"\"self-financed mortgage\"\" you can find a good deal more info about this kind of arrangement. Here is a useful article from Investopedia, here is one from Forbes, and here is one from Nolo. Broadly speaking, the advantages and disadvantages of seller financing are two sides of the same coin: by doing the agreement yourself without bank involvement, you can cut out procedural red tape, delays, and requirements that a bank might insist on --- but in so doing you may expose yourself to risks that those procedures are designed to shield you from. Most obviously, as the seller, you receive only the down payment up front (not the entire purchase price, as you would if the buyer got a bank loan), and if the buyer doesn't follow through on the agreement, you're on your own as far as starting foreclosure, etc. You can read up on some of the linked pages for more details about the pros and cons. In general, as those pages note, seller-financed mortgages are relatively rare. A home is a big purchase, and if you don't know what you're doing it's easy to screw up in a way that could cost you a large amount of money if things go wrong.\"", "title": "" }, { "docid": "566382", "text": "Most states do have a cooling-off period where the buyer can rescind the purchase as well as a legally allowed limit to how long the dealer has to secure financing when they buyer has opted for dealer-financing. If the dealer did inform you during the allowed window, they will refund your down payment minus mileage fees at a state set cost per mile that you used the car. If the dealer did not inform you during the allowed window, depending on the state, they may have to refund the entire down payment. In any case, the problem is that the bank does not want to offer you the loan, you can try to negotiate and have the dealer use what leverage they have to coerce the bank, but there is probably no way for you to force the loan through. Alternatively you can seek your own financing from your own bank or credit union, which will likely allow the sale to go through. UPDATE - Colorado laws allow the dealer 10 days to inform you that they cannot obtain financing on the terms agreed upon in the original contract. That contract contained wording related to the mileage fees. You can find that info on page 8 of the linked PDF under the heading D. USAGE FEE AND MILEAGE CHARGE", "title": "" }, { "docid": "319749", "text": "Again I don't know how well this applies to all finance professions but in my field a lot of what we do is effectively communicate finance and valuation information to clients. Essentially we are contracted to perform analysis, then we write a report conveying the meaning of that analysis to the client. A good amount of the work we do often has legal implications as well so our writing has to stand up to litigation and cross examination. Perhaps being a good writer won't be crucial for your position but in my opinion writing is mostly about how to effectively communicate an idea. In that context writing is very useful in teaching you how to get your message across. I hope that makes sense.", "title": "" }, { "docid": "233479", "text": "The sales manager and/or finance manager applied a rebate that did not apply. It's their fault. They have internal accounts to handle these situations as they do come up from time to time. The deal is done. They have no legal ground.", "title": "" }, { "docid": "391370", "text": "This is not a finance issue, it is a legal one. You need to talk to a lawyer. To save your credit you can pay off the bank now and fight out the details with your ex later. The bank is still owed their money.", "title": "" }, { "docid": "126814", "text": "I'd be a bit concerned about someone who wanted to transact that large of a transaction in cash. Also consider what you are going to do with the funds, if you deposit it, you will need to tell the bank where it comes from. Why does the bank want to know, because most legal businesses don't transact business with large sums of currency.. What does that tell you about the likelihood the person you are about to do business with is a criminal or involved in criminal affairs? The lower bill of sale price might be more than just to dodge taxes, it could be part of money laundering.. If they can turn right around and 'sell' the boat for $10K, or trade it in on a bigger boat for the same amount, and have a bill than says $4K, then they have just come up with a legal explanation for how they made 6 grand. and you could potentially be considered an accomplice if someone is checking up on their finances. Really, is it worth the risk.", "title": "" }, { "docid": "291680", "text": "Absolutely do not ever use one of these loans. These loans will lead you down a long road of huge interest and credit trouble. They are nothing more then legal loan sharks. But I'm sure I don't have to tell the people of /r/finance this. Do I?", "title": "" }, { "docid": "133623", "text": "Mr. Raphael Lilla has been operating as the Executive Director of SBC Group AG Bouchs (Switzerland) since July, 2016. With a professional experience of over 20 years in the legal and finance industries, Mr. Lilla takes pride in his association with the International Society of Business Leaders.", "title": "" }, { "docid": "513367", "text": "This is more legal and less personal finance question. You should immediately lodge a police complaint mentioning that some persons are using your PAN card details for activities not authorized by you. In the meantime also engage the services of a CA and reply back to income tax authorities. Do not ignore the notice.", "title": "" }, { "docid": "486367", "text": "As you point out, the main benefits of a pension/retirement account over a traditional cash/taxable account are the legal and tax benefits. Most Western countries establish a specific legal definition for an account which is often taxed less or not at all relative to taxable accounts and which contains some protection for the owner in case of a bankruptcy. The typical drawbacks for investing within such structures are limited investment choice, limited withdrawal rights (either in terms of age or rate of withdrawal), and maximum contributions. The benefits are usually very clear, and your decision whether or not to open a pension/retirement account should depend on a careful weighing of the benefits and drawbacks. As to whether you may end up with less than you started, that depends on what you invest in. As with all of finance, you must take more risk to get more return. Although the choices inside a pension/retirement account may be worded somewhat differently, they are usually fundamentally no different than some of the most popular investments available for ordinary taxable accounts.", "title": "" }, { "docid": "327428", "text": "\"There are 2 and 3 family houses that have an \"\"owner occupied\"\" clause for certain financing. Of course, one would rent out the extra apartments without question. The key thing is that owner-occupied means just that, occupancy for tax purposes. Just using a small area like an office won't satisfy the requirement, so no, this isn't legal.\"", "title": "" }, { "docid": "300391", "text": "Here is a pretty exhaustive article on that question. Long story short, it is an insurance policy against the possibility that the person selling the property to you doesn't legally own it. If there was some mistake or fraud along the way the proper owner could theoretically repossess the property without you getting your money back. If you are financing the property, it is almost a certainty that the lender will require you to buy it whether you want it or not.", "title": "" }, { "docid": "357280", "text": "I've been an F&I Manager at a new car dealership for over ten years, and I can tell you this with absolute certainty, your deal is final. There is no legal obligation for you whatsoever. I see this post is a few weeks old so I am sure by now you already know this to be true, but for future reference in case someone in a similar situation comes across this thread, they too will know. This is a completely different situation to the ones referenced earlier in the comments on being called by the dealer to return the vehicle due to the bank not buying the loan. That only pertains to customers who finance, the dealer is protected there because on isolated occasions, which the dealer hates as much as the customer, trust me, you are approved on contingency that the financing bank will approve your loan. That is an educated guess the finance manager makes based on credit history and past experience with the bank, which he is usually correct on. However there are times, especially late afternoon on Fridays when banks are preparing to close for the weekend the loan officer may not be able to approve you before closing time, in which case the dealer allows you to take the vehicle home until business is back up and running the following Monday. He does this mostly to give you sense of ownership, so you don't go down the street to the next dealership and go home in one of their vehicles. However, there are those few instances for whatever reason the bank decides your credit just isn't strong enough for the rate agreed upon, so the dealer will try everything he can to either change to a different lender, or sell the loan at a higher rate which he has to get you to agree upon. If neither of those two things work, he will request that you return the car. Between the time you sign and the moment a lender agrees to purchase your contract the dealer is the lien holder, and has legal rights to repossession, in all 50 states. Not to mention you will sign a contingency contract before leaving that states you are not yet the owner of the car, probably not in so many simple words though, but it will certainly be in there before they let you take a car before the finalizing contract is signed. Now as far as the situation of the OP, you purchased your car for cash, all documents signed, the car is yours, plain and simple. It doesn't matter what state you are in, if he's cashed the check, whatever. The buyer and seller both signed all documents stating a free and clear transaction. Your business is done in the eyes of the law. Most likely the salesman or finance manager who signed paperwork with you, noticed the error and was hoping to recoup the losses from a young novice buyer. Regardless of the situation, it is extremely unprofessional, and clearly shows that this person is very inexperienced and reflects poorly on management as well for not doing a better job of training their employees. When I started out, I found myself in somewhat similar situations, both times I offered to pay the difference of my mistake, or deduct it from my part of the sale. The General Manager didn't take me up on my offer. He just told me we all make mistakes and to just learn from it. Had I been so unprofessional to call the customer and try to renegotiate terms, I would have without a doubt been fired on the spot.", "title": "" }, { "docid": "498350", "text": "\"I get it, but I'm just saying it's not as simple as saying \"\"if you can't settle down for a few weeks, you don't really want the job\"\". A person who uses marijuana for medical purposes is not legally protected from these drug tests (the courts have ruled on this), but it may not be reasonable for them to stop taking their medicine for six to twelve weeks. Finance companies sometimes do hair tests, although it's less common.\"", "title": "" }, { "docid": "276466", "text": "Dumb Coder has already given you a link to a website that explains your rights. The only thing that remains is how to execute the return without getting more grief from the dealer. Though the legal aspects are different, I believe the principle is the same. I had a case where I had to rescind the sale of a vehicle in the US. I was within my legal rights to do so, but I knew that when I returned to the dealership they would not be pleased with my decision. I executed my plan by writing a letter announcing my intention to return the vehicle siting the relevant laws involved with a space at the bottom of the letter for the sales person to acknowledge receipt of the letter and indicate that there was no visible damage to the car when the vehicle was returned. I printed two copies of the letter, one for them to keep, and one for me to keep with the signed acknowledgement of receipt. As expected, they asked me to meet with the finance manager who told me that I wouldn't be able to return the car. I thanked him for meeting with me and told him that I would be happy to meet in court if I didn't receive a check within 7 days. (That was his obligation under the local laws that applied.)", "title": "" }, { "docid": "92938", "text": "gnasher729's answer is fundamentally correct and deserves the checkmark, but I'd like to give an economic explanation for how this economically functions. The key point from gnasher729's answer's that the interest rate is 49.9% for one company. While this may be much higher than the equilibrium rate, the true market interest rate, it is not completely unreasonable because of the risk. For credit to be continually produced, default risk must be compensated because this is a cost to the lender. Most are not in business to lose money, so making loans to borrowers that default 40% of the time would make this interest rate reasonable. For UK citizens, this would not be such a problem because the lender can usually pursue the borrower for the balance, but if the borrower can disavow the loan and leave the legal reach of the UK creditors, the collection rate is 0%. The guarantee by the foreign persons not present in the UK is incidental and probably more of a regulatory requirement since the inability to collect from them is just as unlikely. One should always look for the lowest price with at least minimum quality when shopping for anything, but you are right to be apprehensive legally. Read every line and be sure that you yourself understand every clause before signing. If alternative cheaper financing is available, it is probably superior.", "title": "" }, { "docid": "14219", "text": "\"Consumer facing finance is heavily regulated. You are liable for the recommendations you make; if they are based on a black box you risk problems when sued. It is difficult to explain in a court of law why a neural network came to a particular conclusion. It is much easier to provide advice (models) in the \"\"educated counterparty\"\" market. Not only do institutional investors in general expect to pay for a quality advice (consumers in general expect to get online advice for free) but the legal implications are different.\"", "title": "" }, { "docid": "547302", "text": "\"My teacher always says the property interest the beneficiary \"\"holds\"\" or \"\"possesses\"\" is an equitable interest. I might just seem out of place here because it's a legal term and probably not commonplace outside that sphere. But the beneficiaries equitable interest is possessed or held in that regard. From this equitable interest is the income stream. If that just seems like a bunch of gibberish to you than don't mind me, just trying to learn the ins and outs of trusts not the world of finance generally.\"", "title": "" }, { "docid": "228992", "text": "Its participating preferred with a 1x liquidation preference. Very unfriendly for the company owner. Most startups these days are seeded with convertible notes because there's less thinking about the valuation of the company; that question is booted to the series A. its also easier to draw up the legal docs; pretty much a standard loan agreement. Finally, it can be far friendlier for the owner depending on if the note is an uncapped note. This is expensive financing and your friend can definitely find cheaper money if he looks for it.", "title": "" } ]
897	Overexpressing Cnp1 N-tail variants rescues the temperature-sensitive growth defect of scm3-139.	[ { "docid": "14338915", "text": "The mechanisms ensuring specific incorporation of CENP-A at centromeres are poorly understood. Mis16 and Mis18 are required for CENP-A localization at centromeres and form a complex that is conserved from fission yeast to human. Fission yeast sim1 mutants that alleviate kinetochore domain silencing are defective in Scm3(Sp), the ortholog of budding yeast Scm3(Sc). Scm3(Sp) depends on Mis16/18 for its centromere localization and like them is recruited to centromeres in late anaphase. Importantly, Scm3(Sp) coaffinity purifies with CENP-A(Cnp1) and associates with CENP-A(Cnp1) in vitro, yet localizes independently of intact CENP-A(Cnp1) chromatin and is differentially released from chromatin. While Scm3(Sc) has been proposed to form a unique hexameric nucleosome with CENP-A(Cse4) and histone H4 at budding yeast point centromeres, we favor a model in which Scm3(Sp) acts as a CENP-A(Cnp1) receptor/assembly factor, cooperating with Mis16 and Mis18 to receive CENP-A(Cnp1) from the Sim3 escort and mediate assembly of CENP-A(Cnp1) into subkinetochore chromatin.", "title": "Fission Yeast Scm3: A CENP-A Receptor Required for Integrity of Subkinetochore Chromatin" } ]	[ { "docid": "10189634", "text": "CENP-A chromatin forms the foundation for kinetochore assembly. Replication-independent incorporation of CENP-A at centromeres depends on its chaperone HJURP(Scm3), and Mis18 in vertebrates and fission yeast. The recruitment of Mis18 and HJURP(Scm3) to centromeres is cell cycle regulated. Vertebrate Mis18 associates with Mis18BP1(KNL2), which is critical for the recruitment of Mis18 and HJURP(Scm3). We identify two novel fission yeast Mis18-interacting proteins (Eic1 and Eic2), components of the Mis18 complex. Eic1 is essential to maintain Cnp1(CENP-A) at centromeres and is crucial for kinetochore integrity; Eic2 is dispensable. Eic1 also associates with Fta7(CENP-Q/Okp1), Cnl2(Nkp2) and Mal2(CENP-O/Mcm21), components of the constitutive CCAN/Mis6/Ctf19 complex. No Mis18BP1(KNL2) orthologue has been identified in fission yeast, consequently it remains unknown how the key Cnp1(CENP-A) loading factor Mis18 is recruited. Our findings suggest that Eic1 serves a function analogous to that of Mis18BP1(KNL2), thus representing the functional counterpart of Mis18BP1(KNL2) in fission yeast that connects with a module within the CCAN/Mis6/Ctf19 complex to allow the temporally regulated recruitment of the Mis18/Scm3(HJURP) Cnp1(CENP-A) loading factors. The novel interactions identified between CENP-A loading factors and the CCAN/Mis6/Ctf19 complex are likely to also contribute to CENP-A maintenance in other organisms.", "title": "Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly" }, { "docid": "16686383", "text": "The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein-labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation.", "title": "Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in Saccharomyces cerevisiae" }, { "docid": "21425864", "text": "Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of eukaryotic cells and may also serve as sorting signals on proteins and participate in signal transduction. We have isolated a Saccharomyces cerevisiae GPI anchoring mutant, gpi1, using a colony screen for cells blocked in [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first intermediate in GPI synthesis, and is also temperature-sensitive for growth. Completion of the first step in GPI assembly is therefore required for growth of the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be exploited as a target for antifungal or antiparasitic agents.", "title": "A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis." }, { "docid": "26117607", "text": "Down syndrome cell adhesion molecule (Dscam) seems likely to play a key role in the \"alternative adaptive immunity\" that has been reported in invertebrates. Dscam consists of a cytoplasmic tail that is involved in signal transduction and a hypervariable extracellular region that might use a pathogen recognition mechanism similar to that used by the vertebrate antibodies. In our previous paper, we isolated a unique tail-less form of Dscam from Litopenaeus vannamei. In this study, we report the first membrane-bound form of shrimp Dscam: PmDscam was isolated from Penaeus monodon, and it occurred in both membrane-bound and tail-less forms. Phylogenetic analysis showed that while the crustacean Dscams from shrimp and water flea did not share a single subclade, they were distinct from the invertebrate Dscam-like molecules and from the insecta Dscams. In the extracellular region, the variable regions of PmDscam were located in N-terminal Ig2, N-terminal Ig3 and the entire Ig7 domain. The PmDscam extracellular variants and transmembrane domain variants were produced by mutually exclusive alternative splicing events. The cytoplasmic tail variants were produced by exon inclusion/exclusion. Based on the genomic organization of Daphnia Dscam's cytoplasmic tail, we propose a model of how the shrimp Dscam genomic locus might use Type III polyadenylation to generate both the tail-less and membrane-bound forms.", "title": "Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported." }, { "docid": "18676539", "text": "FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a \"clean\" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner.", "title": "Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M." }, { "docid": "57574395", "text": "Defective brain hormonal signaling has been associated with Alzheimer's disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus. Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impairs long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescues synaptic plasticity and memory in AD mouse models. Peripheral overexpression of FNDC5/irisin rescues memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD.", "title": "Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models" }, { "docid": "17671145", "text": "The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.", "title": "ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer" }, { "docid": "4312169", "text": "Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.", "title": "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma" }, { "docid": "13293033", "text": "Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of induced pluripotent stem cells (iPSCs) to model DS phenotypes, as a prototypical complex human disease, we generated bona fide DS and wild-type (WT) nonviral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency and had remarkably similar lineage potency, differentiation kinetics, proliferation, and axon extension at early time points. However, at later time points DS cultures showed a twofold bias toward glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress-induced apoptosis, and this could be prevented by the antioxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy 21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Nonviral DS iPSCs can therefore model features of complex human disease in vitro and provide a renewable and ethically unencumbered discovery platform.", "title": "Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology." }, { "docid": "30675656", "text": "Frizzled family proteins have been described as receptors of Wnt signaling molecules. In Drosophila, the two known Frizzled proteins are associated with distinct developmental processes. Genesis of epithelial planar polarity requires Frizzled, whereas Dfz2 affects morphogenesis by wingless-mediated signaling. Dishevelled is required in both signaling pathways. Here, we use genetic and overexpression assays to show that Dishevelled activates JNK cascades. Rescue analysis reveals different protein domain requirements in Dishevelled for the two pathways; the C-terminal DEP domain is essential to rescue planar polarity defects and induce JNK signaling. Furthermore, the planar polarity-specific dsh1 allele is mutated in the DEP domain. Our results indicate that different Wnt/Fz signals activate distinct intracellular pathways, and Dishevelled discriminates among them by distinct domain interactions.", "title": "Dishevelled Activates JNK and Discriminates between JNK Pathways in Planar Polarity and wingless Signaling" }, { "docid": "2356950", "text": "Methyl-CpG binding protein 1 (MBD1) regulates gene expression via a DNA methylation-mediated epigenetic mechanism. We have previously demonstrated that MBD1 deficiency impairs adult neural stem/progenitor cell (aNSC) differentiation and neurogenesis, but the underlying mechanism was unclear. Here, we show that MBD1 regulates the expression of several microRNAs in aNSCs and, specifically, that miR-184 is directly repressed by MBD1. High levels of miR-184 promoted proliferation but inhibited differentiation of aNSCs, whereas inhibition of miR-184 rescued the phenotypes associated with MBD1 deficiency. We further found that miR-184 regulates the expression of Numblike (Numbl), a known regulator of brain development, by binding to the 3'-UTR of Numbl mRNA and affecting its translation. Expression of exogenous Numbl could rescue the aNSC defects that result from either miR-184 overexpression or MBD1 deficiency. Therefore, MBD1, miR-184, and Numbl form a regulatory network that helps control the balance between proliferation and differentiation of aNSCs.", "title": "Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation." }, { "docid": "23160444", "text": "Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin-coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short- and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.", "title": "Two-tiered coupling between flowing actin and immobilized N-cadherin/catenin complexes in neuronal growth cones." }, { "docid": "7717468", "text": "Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans undergoes phenotypic switching in vivo that promotes persistence in tissue. By microarray and real-time PCR analyses, the allergen 1 gene (ALL1) was found to be downregulated in the hypervirulent mucoid switch variant, both during logarithmic growth and during intracellular growth in macrophages. The ALL1 gene encodes a small cytoplasmic protein that is involved in capsule formation. Growth of an all1Delta gene deletion mutant was normal. Similar to cells of the mucoid switch variant, all1Delta cells produced a larger polysaccharide capsule than cells of the smooth parent and the complemented strain produced, and the enlarged capsule inhibited macrophage phagocytosis. The mutant exhibited a modest defect in capsule induction compared to all of the other variants. In animal models the phenotype of the all1Delta mutant mimicked the hypervirulent phenotype of the mucoid switch variant, which is characterized by decreased host survival and elevated intracranial pressure. Decreased survival is likely the result of both an ineffective cell-mediated immune response and impaired phagocytosis by macrophages. Consequently, we concluded that, unlike loss of most virulence-associated genes, where loss of gene function results in attenuated virulence, loss of the ALL1 gene enhances virulence by altering the host-pathogen interaction and thereby impairing clearance. Our data identified the first cryptococcal gene associated with elevated intracranial pressure and support the hypothesis that an environmental opportunistic pathogen has modified its virulence in vivo by epigenetic downregulation of gene function.", "title": "Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans." }, { "docid": "14471161", "text": "Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbalpha, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by approximately 40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced >10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics.", "title": "Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing." }, { "docid": "23117928", "text": "Infection of Sulfolobus islandicus REY15A with mixtures of different Sulfolobus viruses, including STSV2, did not induce spacer acquisition by the host CRISPR immune system. However, coinfection with the tailed fusiform viruses SMV1 and STSV2 generated hyperactive spacer acquisition in both CRISPR loci, exclusively from STSV2, with the resultant loss of STSV2 but not SMV1. SMV1 was shown to activate adaptation while itself being resistant to CRISPR-mediated adaptation and DNA interference. Exceptionally, a single clone S-1 isolated from an SMV1 + STSV2-infected culture, that carried STSV2-specific spacers and had lost STSV2 but not SMV1, acquired spacers from SMV1. This effect was also reproducible on reinfecting wild-type host cells with a variant SMV1 isolated from the S-1 culture. The SMV1 variant lacked a virion protein ORF114 that was shown to bind DNA. This study also provided evidence for: (i) limits on the maximum sizes of CRISPR loci; (ii) spacer uptake strongly retarding growth of infected cultures; (iii) protospacer selection being essentially random and non-directional, and (iv) the reversible uptake of spacers from STSV2 and SMV1. A hypothesis is presented to explain the interactive conflicts between SMV1 and the host CRISPR immune system.", "title": "Inter-viral conflicts that exploit host CRISPR immune systems of Sulfolobus." }, { "docid": "26625002", "text": "The outer membrane channel TolC is a key component of multidrug efflux and type I secretion transporters in Escherichia coli. Mutational inactivation of TolC renders cells highly susceptible to antibiotics and leads to defects in secretion of protein toxins. Despite impairment of various transport functions, no growth defects were reported in cells lacking TolC. Unexpectedly, we found that the loss of TolC notably impairs cell division and growth in minimal glucose medium. The TolC-dependent phenotype was further exacerbated by the loss of ygiB and ygiC genes expressed in the same operon as tolC and their homologues yjfM and yjfC located elsewhere on the chromosome. Our results show that this growth deficiency is caused by depletion of the critical metabolite NAD(+) and high NADH/NAD(+) ratios. The increased amounts of PspA and decreased rates of NADH oxidation in Delta tolC membranes indicated stress on the membrane and dissipation of a proton motive force. We conclude that inactivation of TolC triggers metabolic shutdown in E. coli cells grown in minimal glucose medium. The Delta tolC phenotype is partially rescued by YgiBC and YjfMC, which have parallel functions independent from TolC.", "title": "Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC." }, { "docid": "24725136", "text": "BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).", "title": "Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination." }, { "docid": "6766459", "text": "Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40 °C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression resulted in increased expression of RBM3-targeted temperature-sensitive miRNAs, we termed thermomiRs. ThermomiRs such as miR-142-5p and miR-143 in turn target endogenous pyrogens including IL-6, IL6ST, TLR2, PGE2 and TNF to complete a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia. Using normal PBMCs that were exogenously exposed to fever-like temperature (40 °C), we further demonstrate the trend by which decreased levels of RBM3 were associated with increased levels of miR-142-5p and miR-143 and vice versa over a 24 h time course. Collectively, our results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142-5p and miR-143.", "title": "RBM3 regulates temperature sensitive miR-142–5p and miR-143 (thermomiRs), which target immune genes and control fever" }, { "docid": "26596106", "text": "In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.", "title": "Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae." }, { "docid": "34016944", "text": "PURPOSE Tyrosine kinase (TK) inhibitors are emerging as a promising new approach to the treatment of HER overexpressing tumors, however optimal use of these agents awaits further definition of the downstream signaling pathways that mediate their effects. We reported previously that both EGFR- and Her2-overexpressing tumors are sensitive to the new EGFR-selective TK inhibitor gefitinib (ZD1839, \"Iressa\"), and sensitivity to this agent correlated with its ability to down-regulate Akt. However, EGFR-overexpressing MDA-468 cells, which lack PTEN function, are resistant to ZD1839, and ZD1839 is unable to down-regulate Akt activity in these cells. EXPERIMENTAL DESIGN To study the role of PTEN function, we generated MDA468 cells with tet-inducible PTEN expression. RESULTS We show here that the resistance of MDA-468 cells to ZD1839 is attributable to EGFR-independent constitutive Akt activation caused by loss of PTEN function in these cells. Reconstitution of PTEN function through tet-inducible expression restores ZD1839 sensitivity to these cells and reestablishes EGFR-stimulated Akt signaling. Although restoration of PTEN function to tumors is difficult to implement clinically, much of the effects of PTEN loss are attributable to overactive PI3K/Akt pathway signaling, and this overactivity can be modulated by pharmacologic approaches. We show here that pharmacologic down-regulation of constitutive PI3K/Akt pathway signaling using the PI3K inhibitor LY294002 similarly restores EGFR-stimulated Akt signaling and sensitizes MDA-468 cells to ZD1839. CONCLUSIONS Sensitivity to ZD1839 requires intact growth factor receptor-stimulated Akt signaling activity. PTEN loss leads to uncoupling of this signaling pathway and results in ZD1839 resistance, which can be reversed with reintroduction of PTEN or pharmacologic down-regulation of constitutive PI3K/Akt pathway activity. These data have important predictive and therapeutic clinical implications.", "title": "Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling." }, { "docid": "22362025", "text": "Small regulatory RNAs are key regulators of gene expression. One class of small regulatory RNAs, termed the endogenous small interfering RNAs (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism termed endogenous RNAi (endo RNAi). A complex of proteins composed of ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo RNAi processes in Caenorhabditis elegans. We conducted a genetic screen to identify additional components of the endo RNAi machinery. Our screen recovered alleles of eri-9, which encodes a novel DICER-interacting protein, and a missense mutation within the helicase domain of DICER [DCR-1(G492R)]. ERI-9(-) and DCR-1(G492) animals exhibit defects in endo siRNA expression and a concomitant failure to regulate mRNAs that exhibit sequence homology to these endo siRNAs, indicating that ERI-9 and the DCR-1 helicase domain function in the C. elegans endo RNAi pathway. We define a subset of Eri mutant animals (including eri-1, rrf-3, eri-3, and dcr-1, but not eri-9 or ergo-1) that exhibit temperature-sensitive, sperm-specific sterility and defects in X chromosome segregation. Among these mutants we find multiple aberrations in sperm development beginning with cytokinesis and extending through terminal differentiation. These results identify novel components of the endo RNAi machinery, demonstrate differential requirements for the Eri factors in the sperm-producing germline, and begin to delineate the functional requirement for the ERI/DICER complex in sperm development.", "title": "Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans." }, { "docid": "10169908", "text": "PURPOSE We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival. EXPERIMENTAL DESIGN To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines. RESULTS Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na(+)-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling. CONCLUSIONS These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.", "title": "SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival." }, { "docid": "12948892", "text": "Evidence has been accumulated that glioblastoma cells release and exploit glutamate for proliferation and migration by autocrine or paracrine loops through Ca2+-permeable AMPA-type glutamate receptors. Here, we show that Ca2+ signaling mediated by AMPA receptor regulates the growth and motility of glioblastoma cells via activation of Akt. Ca2+ supplied through Ca2+-permeable AMPA receptor phosphorylated Akt at Ser-473, thereby facilitating proliferation and mobility. A dominant-negative form of Akt inhibited cell proliferation and migration accelerated by overexpression of Ca2+-permeable AMPA receptor. In contrast, introduction of a constitutively active form of Akt rescued tumor cells from apoptosis induced by the conversion of Ca2+-permeable AMPA receptor to Ca2+-impermeable receptors by the delivery of GluR2 cDNA. Therefore, Akt functions as downstream effectors for Ca2+-signaling mediated by AMPA receptor in glioblastoma cells. The activation of the glutamate-AMPA receptor-Akt pathway may contribute to the high degree of anaplasia and invasive growth of human glioblastoma. This novel pathway might give an alternative therapeutic target.", "title": "Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation." }, { "docid": "22522432", "text": "The stable contact of ISW2 with nucleosomal DNA approximately 20 bp from the dyad was shown by DNA footprinting and photoaffinity labeling using recombinant histone octamers to require the histone H4 N-terminal tail. Efficient ISW2 remodeling also required the H4 N-terminal tail, although the lack of the H4 tail can be mostly compensated for by increasing the incubation time or concentration of ISW2. Similarly, the length of extranucleosomal DNA affected the stable contact of ISW2 with this same internal nucleosomal site, with the optimal length being 70 to 85 bp. These data indicate the histone H4 tail, in concert with a favorable length of extranucleosomal DNA, recruits and properly orients ISW2 onto the nucleosome for efficient nucleosome remodeling. One consequence of this property of ISW2 is likely its previously observed nucleosome spacing activity.", "title": "Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA." }, { "docid": "12225214", "text": "Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminus of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases encoded by Kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompatibility complex class I (MHC I) molecules and subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down-regulation of MHC I molecules lacking lysine residues in their intracytoplasmic domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and their association with ubiquitin was sensitive to beta2-mercaptoethanol, unlike lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a single cysteine residue in an artificial glycine and alanine intracytoplasmic domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination can occur on proteins lacking accessible lysines or an accessible N terminus.", "title": "Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase." }, { "docid": "3127341", "text": "The glucagon-like peptide-1 receptor (GLP-1R) is a key physiological regulator of insulin secretion and a major therapeutic target for the treatment of type II diabetes. However, regulation of GLP-1R function is complex with multiple endogenous peptides that interact with the receptor, including full-length (1-37) and truncated (7-37) forms of GLP-1 that can exist in an amidated form (GLP-1(1-36)NH₂ and GLP-1(7-36)NH₂) and the related peptide oxyntomodulin. In addition, the GLP-1R possesses exogenous agonists, including exendin-4, and the allosteric modulator, compound 2 (6,7-dichloro-2-methylsulfonyl-3-tert-butylaminoquinoxaline). The complexity of this ligand-receptor system is further increased by the presence of several single nucleotide polymorphisms (SNPs) that are distributed across the receptor. We have investigated 10 GLP-1R SNPs, which were characterized in three physiologically relevant signaling pathways (cAMP accumulation, extracellular signal-regulated kinase 1/2 phosphorylation, and intracellular Ca²⁺ mobilization); ligand binding and cell surface receptor expression were also determined. We demonstrate both ligand- and pathway-specific effects for multiple SNPs, with the most dramatic effect observed for the Met¹⁴⁹ receptor variant. At the Met¹⁴⁹ variant, there was selective loss of peptide-induced responses across all pathways examined, but preservation of response to the small molecule compound 2. In contrast, at the Cys³³³ variant, peptide responses were preserved but there was attenuated response to compound 2. Strikingly, the loss of peptide function at the Met¹⁴⁹ receptor variant could be allosterically rescued by compound 2, providing proof-of-principle evidence that allosteric drugs could be used to treat patients with this loss of function variant.", "title": "Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation." }, { "docid": "33076846", "text": "Polyploidization can precede the development of aneuploidy in cancer. Polyploidization in megakaryocytes (Mks), in contrast, is a highly controlled developmental process critical for efficient platelet production via unknown mechanisms. Using primary cells, we demonstrate that the guanine exchange factors GEF-H1 and ECT2, which are often overexpressed in cancer and are essential for RhoA activation during cytokinesis, must be downregulated for Mk polyploidization. The first (2N-4N) endomitotic cycle requires GEF-H1 downregulation, whereas subsequent cycles (>4N) require ECT2 downregulation. Exogenous expression of both GEF-H1 and ECT2 prevents endomitosis, resulting in proliferation of 2N Mks. Furthermore, we have shown that the mechanism by which polyploidization is prevented in Mks lacking Mkl1, which is mutated in megakaryocytic leukemia, is via elevated GEF-H1 expression; shRNA-mediated GEF-H1 knockdown alone rescues this ploidy defect. These mechanistic insights enhance our understanding of normal versus malignant megakaryocytopoiesis, as well as aberrant mitosis in aneuploid cancers.", "title": "Role of RhoA-specific guanine exchange factors in regulation of endomitosis in megakaryocytes." }, { "docid": "435529", "text": "HEN1-mediated 2'-O-methylation has been shown to be a key mechanism to protect plant microRNAs (miRNAs) and small interfering RNAs (siRNAs) as well as animal piwi-interacting RNAs (piRNAs) from degradation and 3' terminal uridylation [1-8]. However, enzymes uridylating unmethylated miRNAs, siRNAs, or piRNAs in hen1 are unknown. In this study, a genetic screen identified a second-site mutation hen1 suppressor1-2 (heso1-2) that partially suppresses the morphological phenotypes of the hypomorphic hen1-2 allele and the null hen1-1 allele in Arabidopsis. HESO1 encodes a terminal nucleotidyl transferase that prefers to add untemplated uridine to the 3' end of RNA, which is completely abolished by 2'-O-methylation. heso1-2 affects the profile of u-tailed miRNAs and siRNAs and increases the abundance of truncated and/or normal sized ones in hen1, which often results in increased total amount of miRNAs and siRNAs in hen1. In contrast, overexpressing HESO1 in hen1-2 causes more severe morphological defects and less accumulation of miRNAs. These results demonstrate that HESO1 is an enzyme uridylating unmethylated miRNAs and siRNAs in hen1. These observations also suggest that uridylation may destabilize unmethylated miRNAs through an unknown mechanism and compete with 3'-to-5' exoribonuclease activities in hen1. This study shall have implications on piRNA uridylation in hen1 in animals.", "title": "Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis" }, { "docid": "4455466", "text": "Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.", "title": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression" }, { "docid": "519974", "text": "Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.", "title": "ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures" } ]
5765	When does it make sense for the money paid for equity to go to the corporation?	[ { "docid": "289656", "text": "If Jack owns all of the one million founding shares (which I assume you meant), and wants to transfer 250,000 shares to Venturo, then he is just personally selling shares to Venturo and the corporation gains nothing. If Jack does not own all of the founding shares, and the corporation had retained some, then the corporate shares could be sold to raise cash for the corporation. Usually in situations like this, the corporation will create more shares, diluting existing shareholders, and then sell the new shares on the open market to raise cash.", "title": "" }, { "docid": "2205", "text": "If the check is written as a check to BigCo, it is less clear how Jack can compensate himself for the equity sale. It is as if the equity was owned by the corporation, not by Jack. This is correct. If the check is written to BigCo, then it is BigCo issuing new shares. Jack doesn't compensate himself for the equity sale, as he didn't sell anything. The company traded shares for money which it uses for expansion. In the long term, the capital gain from expansion may exceed the value of a $200,000 no-interest loan to the company. If the value of the company before investing $250,000 is $1 million, then the value after investing is $1.25 million. So $250,000 is 20% of the value of the company. BigCo should not give the buyer 25% of BigCo but only 20% in that example. If it does give 25%, the buyer is getting a $312,500 stake for only $250,000. With the other example, Jack sells 25% of the company for $250,000 from his personal shares. This doesn't change the assessed value of the company, just Jack's stake. Jack then loans the company $200,000. This also doesn't change the assessed value of the company (at least in theory). It gains $200,000 but has an offsetting debt of $200,000. In net, that's no change. Assets and liabilities balance the same. So if you know that the assessed value of the company is $1 million and that the buyer is paying $250,000 for a 25% stake at that same valuation, then you know that the check is being written to Jack. If the check is written to BigCo, then one or more of those numbers is incorrect. The buyer could be getting a 20% stake. The new value of the company after the investment is $1.25 million. Or paying $333,333.33. The new value of the company after the investment is $1,333,333.33. Or BigCo could only be worth $750,000 before the investment. The new value of the company after the investment is $1 million. Or Jack is getting screwed, selling $312,500 in stock (25%) for only $250,000. Jack's shares drop from being worth $1 million to only $937,500. The value of the company is $1.25 million. Or some combination of smaller changes that balances.", "title": "" }, { "docid": "303810", "text": "The check is written to BigCo. Jack is being diluted, corporation issues more shares. There's no gain, no change in Jack's equity value. Jack didn't lose or win anything. BigCo was worth $1M before the additional money, it is worth $1.25M after the additional money, with Jack owning the same $1M, but the cake is now bigger (obviously the numbers are wrong in your example, but you get the point).", "title": "" }, { "docid": "121622", "text": "\"BigCo is selling new shares and receives the money from Venturo. If Venturo is offering $250k for 25% of the company, then the valuation that they are agreeing on is a value of $1m for the company after the new investment is made. If Jack is the sole owner of one million shares before the new investment, then BigCo sells 333,333 shares to Venturo for $250k. The new total number of shares of BigCo is 1,333,333; Venturo holds 25%, and Jack holds 75%. The amount that Jack originally invested in the company is irrelevant. At the moment of the sale, the Venturo and Jack agree that Jack's stake is worth $750k. The value of Jack's stake may have gone up, but he owes no capital gains tax, because he hasn't realized any of his gains yet. Jack hasn't sold any of his stake. You might think that he has, because he used to hold 100% and now he holds 75%. However, the difference is that the company is worth more than was before the sale. So the value of his stake was unchanged immediately before and after the sale. Jack agrees to this because the company needs this additional capital in order to meet its potential. (See \"\"Why is stock dilution legal?\"\") For further explanation and another example of this, see the question \"\"If a startup receives investment money, does the startup founder/owner actually gain anything?\"\" Your other scenario, where Venturo purchases existing shares directly from Jack, is not practical in this situation. If Jack sells his existing shares, you are correct that the company does not gain any additional capital. An investor would not want to invest in the company this way, because the company is struggling and needs new capital.\"", "title": "" } ]	[ { "docid": "115814", "text": "Does it make sense for stocks to earn a premium indefinitely? Yes. There is good reason to think that the stock market will make money indefinitely: the stock market is the primary mechanism through which investors bear market risk, which requires compensation. If you think of all the owners of firms (stockholders and bondholders, generally) the risk premium that stocks earn stocks is the way bondholders pay equityholders to bear the risk that they do not wish to. Will stock prices always go up in the long run? As long as companies pay out less in dividends than their profit, prices will go up. That could change if we were to change our corporate culture and/or tax practices so that firms paid out more in dividends. However, for the purposes of your question, I think it doesn't matter much whether the investor makes money as dividends or capital gains. Does the 5-7% guess apply only to the US market? I didn't write (nor read) the books in question, but most likely that is a global number. The US dominates the global equity market, so it's often a good proxy. However, international returns taken together have no less risk and earn no less over long horizons in general. The particular examples you have pointed out are special cases that only apply to a part of the global economy and a particular time period. There are plenty of examples of stock markets and time periods that did much better than the US market to offset your examples. Is 5-7% a reasonable long-term estimate of equity returns? Equity will always earn more in expectation than risk-free securities will. How much more depends on major economic factors. 5-7% has been a good estimate for the market risk premium for many, many decades (stocks should earn this plus whatever the risk-free rate is). However, that is just an empirical observation, not a rule. It can change. Some day technological progress could slow down or stop, we could run out of important resources in a way that we can't compensate for, our population permanently could stop growing, aliens could invade, etc. Down the road it is certainly possible for expected equity returns to go down and never go back up again. This would result from a permanent, global, economic shift that I think would be pretty obvious. That is, you wouldn't have to look at stock prices to know it was happening.", "title": "" }, { "docid": "235484", "text": "\"Is all interest on a first time home deductible on taxes? What does that even mean? If I pay $14,000 in taxes will My taxes be $14,000 less. Will my taxable income by that much less? If you use the standard deduction in the US (assuming United States), you will have 0 benefit from a mortgage. If you itemize deductions, then your interest paid (not principal) and your property tax paid is deductible and reduces your income for tax purposes. If your marginal tax rate is 25% and you pay $10000 in interest and property tax, then when you file your taxes, you'll owe (or get a refund) of $2500 (marginal tax rate * (amount of interest + property tax)). I have heard the term \"\"The equity on your home is like a bank\"\". What does that mean? I suppose I could borrow using the equity in my home as collateral? If you pay an extra $500 to your mortgage, then your equity in your house goes up by $500 as well. When you pay down the principal by $500 on a car loan (depreciating asset) you end up with less than $500 in value in the car because the car's value is going down. When you do the same in an appreciating asset, you still have that money available to you though you either need to sell or get a loan to use that money. Are there any other general benefits that would drive me from paying $800 in rent, to owning a house? There are several other benefits. These are a few of the positives, but know that there are many negatives to home ownership and the cost of real estate transactions usually dictate that buying doesn't make sense until you want to stay put for 5-7 years. A shorter duration than that usually are better served by renting. The amount of maintenance on a house you own is almost always under estimated by new home owners.\"", "title": "" }, { "docid": "538490", "text": "An equity tax does seem to make some sense. It would probably help to stave off deflation as well because it would encourage growth and investment where people would otherwise choose to sit on their money or worse. An equity tax on currency or liquid investments of even .5% APR would have a huge effect on the behavior of corporations. Sadly the largest of them would have the resources to avoid the tax by keeping all of their money out of the country.", "title": "" }, { "docid": "42625", "text": "\"This question drives at what value a shareholder actually provides to a corporation, and by extent, to the economy. If you subscribe for new shares (like in an Initial Public Offering), it is very straightforward to say \"\"I have provided capital to the corporation, which it is using to advance its business.\"\" If you buy shares that already exist (like in a typical share purchase on a public exchange), your money doesn't go to the company. Instead, it goes to someone who paid someone who paid someone who paid someone (etc.) who originally contributed money to the corporation. In theory, the value of a share price does not directly impact the operation of the company itself, apart from what @DanielCarson aptly noted (employee stock options are affected by share price, impacting morale, etc.). This is because in theory, the true value of a company (and thus, the value of a share) is the present value of all future cashflows (dividends + final liquidation). This means that in a technical sense, a company's share price should result from the company's value. The company's true value does not result from the share price. But what you are doing as a shareholder is impacting the liquidity available to other potential investors (also as mentioned by @DanielCarson, in reference to the desirability for future financing). The more people who invest their money in the stock market, the more liquid those stocks become. This is the true value you add to the economy by investing in stocks - you add liquidity to the market, decreasing the risk of capital investment generally. The fewer people there are who are willing to invest in a particular company, the harder it is for an investor to buy or sell shares at will. If it is difficult to sell shares in a company, the risk of holding shares in that company is higher, because you can't \"\"cash out\"\" as easily. This increased risk then does change the value of the shares - because even though the corporation's internal value is the same, the projected cashflows of the shares themselves now has a question mark around the ability to sell when desired. Whether this actually has an impact on anything depends on how many people join you in your declaration of ethical investing. Like many other forms of social activism, success relies on joint effort. This goes beyond the direct and indirect impacts mentioned above; if 'ethical investing' becomes more pronounced, it may begin to stigmatize the target companies (fewer people wanting to work for 'blacklist' corporations, fewer people buying their products, etc.).\"", "title": "" }, { "docid": "345681", "text": "\"Equity does not represent production divisions in a company (i.e. chocolate, strawberry, and vanilla does not make sense). In Sole proprietorship, equity represents 1 owner. In Partnership, equity has at least two sub-accounts, namely Partner 1 and Partner 2. In Corporations, equity may have Common Stockholders and Preferred Stockholders, or even different class of shares for insiders and angel investors. As you can see, equity represents who owns the company. It is not what the company does or manufactures. First and foremost, define the boundary of the firm. Are your books titled \"\"The books of the family of Doe\"\", \"\"The books of Mr & Mrs Doe\"\", or \"\"The books of Mr & Mrs Doe & Sons\"\". Ask yourself, who \"\"owns\"\" this family. If you believe that a marriage is perpetual until further notice then it does not make any sense to constantly calculate which parent owns the family more. In partnership, firm profits are attributed to partner's accounts using previously agreed ratio. For example, (60%/40% because Partner 1 is more hard working and valuable to the firm. Does your child own this family? Does he/she have any rights to use the assets, to earn income from the assets, to transfer the assets to others, or to enforce private property rights? If they don't have a part of these rights, they are certainly NOT part of Equity. So what happens to the expenses of children if you follow the \"\"partnership\"\" model? There are two ways. The first way is to attribute the Loss to the parents/family since you do not expect the children to repay. It is an unrecoverable loss written off. The second way is to create a Debtor(Asset) account to aggregate all child expense, then create a separate book called \"\"The books Children 1\"\", and classify the expense in that separate book. I advise using \"\"The family of Doe\"\" as the firm's boundary, and having 1 Equity account to simplify everything. It is ultimately up to you to decide the boundaries.\"", "title": "" }, { "docid": "3750", "text": "\"The implication is market irrationality is stronger than market rationality. Aka nothing makes sense when TSLA climbs to $400 or when CMG rises to $750. I wouldn't say there is a systematic flaw in valuation. I think there is just a lot of ignorance. Markets are more open to household investors than ever before. You used to go to your broker and ask him what's up and he'd give you the inside scoop since you pay them money. Now you go onto marketwatch and get some random nobody's opinion on everything and make stock selections based on that. But eventually the chickens come home to roost and things will correct itself. Big players will jump ship and cause signals to other traders to jump ship. The public can pump stocks up pretty high but it doesn't just go to infinity. Eventually someone will stop and say, \"\"wtf is going on\"\" and start selling. Stocks are sold on a basis of a limit order book so it's real prices that people are paying. People don't care about prices currently because most don't have any finance knowledge but want to invest their own money. They just hear about Tesla doing something amazing (from some clickbait article or news outlet) and can't stop thinking about buying Tesla. They go to Chipotle and think \"\"wow this place is so good and hip, they must be a great investment\"\". The markets have been filled with more subjective analysis than ever before especially with so much low quality information at your fingertips. Equally ignorant people startin blogs about investment and personal finance being shepherds for other ignorant people. In the end they all lose. People who exclaim \"\"this stock is going up to $250 easily\"\" with literally zero quantitative analysis or even a baseline reference point to back it up are prime examples of this. Ignorance of markets and cheap money almost always lead to market runs that end catastrophically. Dot com bubble, 1929 market crash, 2008, it's always the same. People who have no business taking loans out or buying on margin or leveraging positions with debt only to get fucked over once things are brought back down to Earth. After 2 runs of QE, we now have cheap money and with everyone being a crier for their personal investment strategy, we now also have rampant ignorance. I don't expect things to last but no one can call the bottom or the top, or else you'd be very very rich. Have a safe portfolio, don't try to time the markets. Have a strategy that hedges against unexpected change, don't try to gamble on this change. Because it's ultimately impossible to predict the movement of every single person on this earth that invests their money into markets. So don't try. Just be prepared. ---- To expand further into valuation theory: at the end of the day, people invest their money to make more money. It's as simple as that. If your money doesn't grow in an investment vehicle, it's ultimately a shit investment. But no one values intrinsic value of a company's equity before they decide whether or not $380 for TSLA is a good/bad deal. As a result, stocks can be pumped up way higher and people still see the gains on their stocks through capital gains fueled by other optimistic investors. Non-zero sum goes both ways. People can make shitloads of money on stock without an equitable loser--people can also lose shitloads on stock without any real winner emerging from the rubble. When this bubble bursts, lots and lots of people will lose money on TSLA when people's expectations become rational and they stop paying $300 a share for a negative or 70 PE ratio. It's insane what multipliers people will pay for these companies without even realizing the implication--if you buy a share of a company with a PE ratio of 70, you just paid 70 times their earnings for a share. In an ideal world where they released every single penny of earnings as dividends, it would take you 70 periods to reclaim your money on that share. This obviously doesn't take into account capital gains, but capital gains aren't supposed to be this irrational to where a stock can be pumped up into 70x PE ratio in the first place. It's a whole messed up web of confusion and irrationality and eventually something will catalyze a reaction. Imagine a market where everyone just agreed to pump up a single stock to infinity and everyone just rakes in shitloads of money. Would this work? Of course not. It's literally a pyramid scheme that relies on future generations to constantly inject capital--no real value is being created by this scheme. It requires constantly more future generations to continue adding money into the scheme and will crash once people stop pumping money into it. The same thing will happen here. Everyone \"\"agreed\"\" to pump up TSLA (in a sense) but eventually people will realize this is stupid as shit and the pyramid will come tumbling down because there is nothing they receive from this scheme other than the money from other people. It's essentially moving money around, making 0 use of it, until people stop pumping money into the system and everyone realizes that nothing of real value had been produced through the use of this money. Ultimately the only thing that creates real value is the money that is returned to shareholders from an outside party--the company you're invested in. Real value is not created when people exchange stock and money. So why do these transactions create higher values in equity? The basis of equity valuation states that dividends are the only way for companies to raise the price of their stock, going off the traditional Dividend Discount Model. And theoretically, that's the only logical explanation. Buying and trading stock does nothing for the company, minus T Stock they might own. Ultimately the only party creating real value is the underlying company. If they aren't creating real value, then their stock should not be increasing, period. The way they create value is by efficiently utilizing assets to generate returns on investment which can be returned to investors through dividends. Dividends can only be increased (while maintaining an equitable payout ratio) by generating more net income that can increase the actual pool of money that can be allocated back to investors. TSLA does not do this. TSLA regularly loses money and overpromises. There is no logical explanation for any of this except that everyone is irrational. Obviously theory is not the same as in practice but the theory is important here because it's really the basis for any investment at all. At the end of the day, a share of stock is the right to a share of the company's equity. People own equity in companies because companies generate money that it returns back to its owners. That's what a company does. That's what an owner does. If you own shares of a company, you're an owner. And if your company does not return more money back to you YoY, then why are you invested in them? Ultimately, you're riding a capital gains wave that will eventually subside once market irrationality succumbs to rationality. And it always does because the real value always catches up to the fake value that is caused by pumping and dumping stocks.\"", "title": "" }, { "docid": "149493", "text": "\"For this to work, those who control the dilution must also control their salaries because the only way for them to be paid off when it's the corporation itself selling is to gain access to the proceeds. When a corporation sells newly issued equity, the corporation itself owns the money. To at least have the appearance of propriety, the scammers must be paid those proceeds. Both actions imply that the board is captured by the scammers. There are many corporations that seem to do this even with persistently large market capitalizations. The key difference between this and pump-and-dump is that its a fraudulent group of investors selling in this case instead of the corporation itself. A detailed simple example Corporations are mandated by law to be little oligarchies; although, \"\"republic\"\" is now becoming more appropriate with all of the new shareholder rights. A corporation is controlled at root by the board of directors who are elected by the shareholders. The board has no direct operational control, as that is left to the \"\"king\"\", the CEO; however, the board does control what everyone wants access to: the money. Board members have all sorts of legal qualitative mandates on how to behave, and they've functioned fairly decently efficiently over the long run, but there are definitely some bad apples. Boards are somewhat intransigent since it's difficult to hold board elections, and usually only specific board members are put up for election by a shareholder vote, so a bad one has the potential to really get stuck in there. Once a bad one is in there, they don't care because they know it will be tough to get them out, so they run roughshod over the company's purse. Only the board can take action on major funding such as the CEO's operating budget, board compensation, financing, investment, etc, some with shareholder approval, some without. The corporation itself owns all of those assets, but the board controls them. In this example, they scheme with most likely the top executive, but a rubber stamp top executive could allow a lower rung to scheme with the board, but the board is always constant until the law is changed. Because there's no honor amongst thieves, the board votes which can require some combination of executive and shareholder approval are taken very close together: sell shares, increase salaries to key executive schemers, increase board compensation. The trusting shareholders believe this is in the best interests of the company at large so go along. So the money flows from existing & new shareholders to the corporation now controlled by a malicious board and then finally to the necessary malicious executive and the vital malicious board.\"", "title": "" }, { "docid": "512429", "text": "\"So some background here - when corporations, large ones have to deal with tax, they generally try to avoid as much tax as possible. Since there are places that are \"\"tax havens\"\" where there is less to even no tax on profit, a lot of money gets routed there to avoid taxes in other places (US or other unfavorable countries). The problem with this from an IRS/government view is that they keep losing millions/billions of dollars in money because of this. I think the corporate federal tax rate is around 35% and that is without state taxes. Unfortunately when you have less and less money at home - less investment at home happens. Corporations stop doing business at home because they have more money somewhere else - and it makes sense to move more of the company to where the money is or to more favorable tax locations. Even worse - the corporation might just \"\"save\"\" its money somewhere else and kill all reinvestment - thus the money is effectively dead to the rest of the economy. There is a lot of talk about a 'one-time' repatriation tax to allow companies that have dodged their tax burdens to have their money come back to the US (and thus can be used locally) at 10% instead of 35% since there is theroretically a vast amount of cash that would be injected into the US economy. The government is hoping this stimulation will help GDP grow, taxes grow, and help the economy as a whole. In reality, it will reward corporations that broke the law (even though everyone does it), and probably just go into savings accounts here in the US - and not be the \"\"silver bullet\"\" to the economy on verge of collapse again.\"", "title": "" }, { "docid": "399191", "text": "\"what does negative Total Equity means in McDonald's balance sheet? It means that their liabilities exceed their total assets. Usually is means that a company has accumulated losses over time, but that's just one explanation. But, isn't McDonald a very healthy company, and never lost money? Just because a company has \"\"always\"\" money does not mean it's a healthy company. It may have borrowed a lot of money in order to operate, and now the growth is not able to keep up with the debt load. In McDonald's case, the major driver in the equity change is the fact that they have bought back over $20 Billion in stock over the past few years, which reduces assets and equity. If they had instead paid off debt, their equity would not be negative, but their debt may be so cheap (in terms of interest rate) that it made more financial sense to buy back stock instead of paying off debt. There are too many variables to assess that in this forum.\"", "title": "" }, { "docid": "333755", "text": "\"There are many different methods for a corporation to get money, but they mostly fall into three categories: earnings, debt and equity. Earnings would be just the corporation's accumulation of cash due to the operation of its business. Perhaps if cash was needed for a particular reason immediately, a business may consider selling a division or group of assets to another party, and using the proceeds for a different part of the business. Debt is money that (to put it simply) the corporation legally must repay to the lender, likely with periodic interest payments. Apart from the interest payments (if any) and the principal (original amount leant), the lender has no additional rights to the value of the company. There are, basically, 2 types of corporate debt: bank debt, and bonds. Bank debt is just the corporation taking on a loan from a bank. Bonds are offered to the public - ie: you could potentially buy a \"\"Tesla Bond\"\", where you give Tesla $1k, and they give you a stated interest rate over time, and principal repayments according to a schedule. Which type of debt a corporation uses will depend mostly on the high cost of offering a public bond, the relationships with current banks, and the interest rates the corporation thinks it can get from either method. Equity [or, shares] is money that the corporation (to put it simply) likely does not have a legal obligation to repay, until the corporation is liquidated (sold at the end of its life) and all debt has already been repaid. But when the corporation is liquidated, the shareholders have a legal right to the entire value of the company, after those debts have been paid. So equity holders have higher risk than debt holders, but they also can share in higher reward. That is why stock prices are so volatile - the value of each share fluctuates based on the perceived value of the entire company. Some equity may be offered with specific rules about dividend payments - maybe they are required [a 'preferred' share likely has a stated dividend rate almost like a bond, but also likely has a limited value it can ever receive back from the corporation], maybe they are at the discretion of the board of directors, maybe they will never happen. There are 2 broad ways for a corporation to get money from equity: a private offering, or a public offering. A private offering could be a small mom and pop store asking their neighbors to invest 5k so they can repair their business's roof, or it could be an 'Angel Investor' [think Shark Tank] contributing significant value and maybe even taking control of the company. Perhaps shares would be offered to all current shareholders first. A public offering would be one where shares would be offered up to the public on the stock exchange, so that anyone could subscribe to them. Why a corporation would use any of these different methods depends on the price it feels it could get from them, and also perhaps whether there are benefits to having different shareholders involved in the business [ie: an Angel investor would likely be involved in the business to protect his/her investment, and that leadership may be what the corporation actually needs, as much or more than money]. Whether a corporation chooses to gain cash from earnings, debt, or equity depends on many factors, including but not limited to: (1) what assets / earnings potential it currently has; (2) the cost of acquiring the cash [ie: the high cost of undergoing a public offering vs the lower cost of increasing a bank loan]; and (3) the ongoing costs of that cash to both the corporation and ultimately the other shareholders - ie: a 3% interest rate on debt vs a 6% dividend rate on preferred shares vs a 5% dividend rate on common shares [which would also share in the net value of the company with the other current shareholders]. In summary: Earnings would be generally preferred, but if the company needs cash immediately, that may not be suitable. Debt is generally cheap to acquire and interest rates are generally lower than required dividend rates. Equity is often expensive to acquire and maintain [either through dividend payments or by reduction of net value attributable to other current shareholders], but may be required if a new venture is risky. ie: a bank/bondholder may not want to lend money for a new tech idea because it is too risky to just get interest from - they want access to the potential earnings as well, through equity.\"", "title": "" }, { "docid": "108770", "text": "\"A bit strange but okay. The way I would think about this is again that you need to determine for what purpose you're computing this, in much the same way you would if you were to build out the model. The IPO valuation is not going to be relevant to the accretion/dilution analysis unless you're trying to determine whether the transaction was net accretive at exit. But that's a weird analysis to do. For longer holding periods like that you're more likely to look at IRR, not EPS. EPS is something investors look at over the short to medium term to get a sense of whether the company is making good acquisition decisions. And to do that short-to-medium term analysis, they look at earnings. Damodaran would say this is a shitty way of looking at things and that you should probably be looking at some measure of ROIC instead, and I tend to agree, but I don't get paid to think like an investor, I get paid to sell shit to them (if only in indirect fashion). The short answer to your question is that no, you should not incorporate what you are calling liquidation value when determining accretion/dilution, but only because the market typically computes accretion/dilution on a 3-year basis tops. I've never put together a book or seen a press release in my admittedly short time in finance that says \"\"the transaction is estimated to be X% accretive within 4 years\"\" - that just seems like an absurd timeline. Final point is just that from an accounting perspective, a gain on a sale of an asset is not going to get booked in either EBITDA or OCF, so just mechanically there's no way for the IPO value to flow into your accretion/dilution analysis there, even if you are looking at EBITDA/shares. You could figure the gain on sale into some kind of adjusted EBITDA/shares version of EPS, but this is neither something I've ever seen nor something that really makes sense in the context of using EPS as a standardized metric across the market. Typically we take OUT non-recurring shit in EPS, we don't add it in. Adding something like this in would be much more appropriate to measuring the success of an acquisition/investing vehicle like a private equity fund, not a standalone operating company that reports operational earnings in addition to cash flow from investing. And as I suggest above, that's an analysis for which the IRR metric is more ideally situated. And just a semantic thing - we typically wouldn't call the exit value a \"\"liquidation value\"\". That term is usually reserved for dissolution of a corporate entity and selling off its physical or intangible assets in piecemeal fashion (i.e. not accounting for operational synergies across the business). IPO value is actually just going to be a measure of market value of equity.\"", "title": "" }, { "docid": "79411", "text": "\"This is not an end-all answer but it'll get you started I have been through accounting courses in college as well as worked as a contractor (files as sole proprietor) for a few years but IANAA (I am not an accountant). Following @MasonWheeler's answer, if you're making that much money you should hire a bean counter to at least overlook your bookkeeping. What type of business? First, if you're the sole owner of the business you will most likely file as a sole proprietorship. If you don't have an official business entity, you should get it registered officially asap, and file under that name. The problem with sole proprietorships is liability. If you get sued, not only are your business' assets vulnerable but they can go after your personal assets too (including house/cars/etc). Legally, you and your business are considered one and the same. To avoid liability issues, you could setup a S corporation. Basically, the business is considered it's own entity and legal matters can only take as much as the business owns. You gain more protection but if you don't explicitly keep your business finances separate from your personal finances, you can get into a lot of trouble. Also, corporations generally pay out more in taxes. Technically, since the business is it's own entity you'll need to pay yourself a 'reasonable salary'. If you skip the salary and pay yourself the profits directly (ie evade being taxed on income/salary) the IRS will shut you down (that's one of the leading causes of corporations being shut down). You can also pay distribute bonuses on top of that but it would be wise to burn the words 'within reason' into your memory first. The tax man gets mad if you short him on payroll taxes. S corporations are complicated, if you go that route definitely seek help from an accountant. Bookkeeping If you're not willing to pay a full time accountant you'll need to do a lot of studying about how this works. Generally, even if you have a sole proprietorship it's best to have a separate bank account for all of your business transactions. Every source/drain of money will fall into one of 3 categories... Assets - What your business owns: Assets can be categorized by liquidity. Meaning how fast you can transform them directly into cash. Just because a company is worth a lot doesn't necessarily mean it has a lot of cash. Some assets depreciate (lose value over time) whereas some are very hard to transform back into cash based on the value and/or market fluctuations (like property). Liabilities - What you owe others and what others owe you: Everything you owe and everything that is owed to you gets tracked. Just like credit cards, it's completely possible to owe more than you own as long as you can pay the interest to maintain the loans. Equity - the net worth of the company: The approach they commonly teach in schools is called double-entry bookkeeping where they use the equation: In practice I prefer the following because it makes more sense: Basically, if you account for everything correctly both sides of the equation should match up. If you choose to go the sole proprietorship route, it's smart to track everything I've mentioned above but you can choose to keep things simple by just looking at your Equity. Equity, the heart of your business... Basically, every transaction you make having to do with your business can be simplified down to debits (money/value) increasing and credits (money/value) decreasing. For a very simple company you can assess this by looking at net profits. Which can be calculated with: Revenues, are made up of money earned by services performed and goods sold. Expenses are made up of operating costs, materials, payroll, consumables, interest on liabilities, etc. Basically, if you brought in 250K but it cost you 100K to make that happen, you've made 150K for the year in profit. So, for your taxes you can count up all the money you've made (Revenues), subtract all of the money you've paid out (Expenses) and you'll know how much profit you've made. The profit is what you pay taxes on. The kicker is, there are gray areas when it comes to deducting expenses. For instance, you can deduct the expense of using your car for business but you need to keep a log and can only expense the miles you traveled explicitly for business. Same goes for deducting dedicated workspaces in your house. Basically, do the research if you're not 100% sure about a deduction. If you don't keep detailed books and try to expense stuff without proof, you can get in trouble if the IRS comes knocking. There are always mythical stories about 'that one guy' who wrote off his boat on his taxes but in reality, you can go to jail for tax fraud if you do that. It comes down to this. At the end of the year, if your business took in a ton of money you'll owe a lot in taxes. The better you can justify your expenses, the more you can reduce that debt. One last thing. You'll also have to pay your personal federal/state taxes (including self-employment tax). That means medicare/social security, etc. If this is your first foray into self-employment you're probably not familiar with the fact that 1099 employers pick up 1/2 of the 15% medicare/social security bill. Typically, if you have an idea of what you make annually, you should be paying this out throughout the year. My pay as a contractor was always erratic so I usually paid it out once/twice a year. It's better to pay too much than too little because the gov't will give you back the money you overpaid. At the end of the day, paying taxed sucks more if you're self-employed but it balances out because you can make a lot more money. If as you said, you've broken six figures, hire a damn accountant/adviser to help you out and start reading. When people say, \"\"a business degree will help you advance in any field,\"\" it's subjects like accounting are core requirements to become a business undergrad. If you don't have time for more school and don't want to pay somebody else to take care of it, there's plenty of written material to learn it on your own. It's not rocket surgery, just basic arithmetic and a lot of business jargon (ie almost as much as technology).\"", "title": "" }, { "docid": "410874", "text": "\"all the other answers are spot on, but look at it this way. really all you mean when you say \"\"building equity\"\" is \"\"accumulating wealth\"\". if that is the goal, then having her invest the money in a brokerage (e.g. ira) account makes a lot more sense. if you can't afford the apartment without her, then you can't afford to pay out her portion of the equity in the future. which means she is not building equity, you are just borrowing money from her. the safest and simplest thing for you to do is to agree on a number that does not include \"\"equity\"\". to be really safe, you might want to both sign something in writing that says she will never have an equity stake unless you agree to it in writing. it doesn't have to be anything fancy. in fact, the shorter the better. i am thinking about 3 sentences should do the trick. if you feel you absolutely have to borrow money from her on a monthly basis to afford your mortgage, then i recommend you make it an unsecured loan. just be sure to specify the interest rate (even if it is zero), and the repayment terms (and ideally, late payment penalties). again, nothing fancy, 10 sentences maybe. e.g. \"\"john doe will borrow x$ per month, until jane doe vacates the apartment. after such time, john doe will begin repaying the loan at y$ per month....\"\" that said, borrowing money from friends and family almost never turns out well. at the very least, you need to save up a few months of rent so that if you do break up, you have time to find another roommate. disclaimer: i do not have any state-issued professional licenses.\"", "title": "" }, { "docid": "159590", "text": "Is she entitled to more of the equity because she made more? No. Equity should be determined by how much each paid. But she is entitled to more of the equity if she paid more. And that may be what she is saying. That she contributed more to the household's finances than you did. If you always paid the mortgage out of the joint account, you could presumably go back and look at the account to find out how much each of you contributed to it. That would give you a reasonable split for the remainder of the equity after your initial investment. If you both put your entire paychecks into the joint account every time, then it will be the same as the ratio of what you each made. That would also make sense for splitting up whatever remains in that account. While you're doing that, you may want to ask for more for your original $65,000. By my calculation, if your mortgage was 3.5%, that $65,000 saved the household more than $12,000 in interest that became equity instead. So you could reasonably bump your return on the initial investment up to $77,000 while making the concession on the rest of the equity. This is just a suggestion for a framework for splitting the equity. If you can agree on a split, it will almost certainly be easier than going to a mediator or court.", "title": "" }, { "docid": "306149", "text": "Fully Paid up Partly Paid up: A company may issue stock to you which is only partly paid up, for example, a company may issue a stock of face value 10 to you and ask you to pay 5 now and other 5 will be adjusted later by some other mechanism. This stock shall be partly paid up. Usually, these stocks are issued in different circumstances, for example as part payment for debentures, preference shares or other capital structuring. On the other hand for a fully paid up share no more money needs to be paid by you or no other adjustments need to be made. So, above, the company is issuing you with stocks for which you will need to pay no further money, they are fully paid for. Authorized Capital: Authorized capital of a company is the amount of money a company can raise by selling stock (not debt, equity). This number is registered when the company is incorporated, subsequently, this number can be revised upward by applying to the registrar of companies. Now, this means that at max. the company is authorized to raise this much capital and no more. However, a company may raise less than this, which is called Issued Capital. In your case, the company is raising its authorized capital by applying to the registrar of companies, though in this case they are looking at their full authorized capital to be issued capital, it was not necessary to do so. Increase of Authorized capital: The main benefit is that the company can get more money in form of equity and utilize the same, perhaps, for expansion of business etc., that is the primary benefit. Bonus Share: Usually, companies keep some surplus as reserve, this money comes out of the profit the company makes and is essentially money of the shareholders. This reserve surplus is maintained for situations, when the money may be required for exigencies. However, this surplus grows over a few years and the company usually the company plans for an expansion of business. However, this money cannot be just taken, as it belongs to the shareholder, so shareholders are issued extra equity in proportion to their current holding and this surplus is capitalized i.e. used as part of the company's equity capital. Bonus declaration does not add t o the value of the company and the share prices fall in proportion (but not quite) to the bonus.", "title": "" }, { "docid": "314056", "text": "This question is indeed rather complicated. Let's simplify it a little bit. Paying down your mortgage makes sense if your expected return in the rest of your portfolio is less than the cost of the mortgage. In many cases, people may also decide to pay down their mortgage because they are risk-averse and do not like carrying debt. There's no tax benefit to doing so, though; Canada doesn't generally allow you to write off mortgage interest, unlike the U.S. As to keeping money in the corporation or not, I'm not going to address that. I don't have a firm enough understanding of corporate taxation. Canadian Couch Potato advises treating all of your investment assets as one large portfolio. That is what you are trying to do here. However, let's consider a different approach. If you do not have enough money to max out your RRSP or TFSA, you may choose to keep your TFSA for an emergency fund, where the money is kept highly liquid. Keep your cash in an interest-bearing TFSA, or perhaps invest it in the money market, inside your TFSA. Then, use your RRSP for the rest of your investment money, split according to your investment goals. This is not the most tax-efficient approach, but it is nice and simple. But you are looking for the most tax-efficient approach. So, let's assume you have enough to more than max out your TFSA and RRSP contributions, and all of your investments are going toward your retirement, which is at least a decade away. Because you are not taxed on your investment income from RRSPs (until you withdraw the money) or TFSA, it makes sense to hold the least tax-efficient investments there. Tax-advantaged investments such as Canadian equities should be held in your investment accounts outside of TFSA and RRSPs. Again, the Canadian Couch Potato has a great article on where to put your investment assets. That article covers interest, dividends, foreign dividends, and capital gains, as well as RRSPs, RESPs, and TFSAs. That article recommends holding Canadian equities in a taxable account, REITs in a tax-sheltered account (TFSA or RRSP), bonds, GICs, and money-market funds in a tax-sheltered account (as these count as interest). The article goes into rather more detail than this, and is worth checking out. It mentions the 15% withholding tax on US-listed ETFs, for example. In addition to that website, I recommend the following three books: The above three resources strongly advocate passive indexed investments, which I like but not everyone agrees with. All three specifically discuss tax implications, which is why I include them here.", "title": "" }, { "docid": "80913", "text": "\"It should be pretty obvious that without knowing what sort of assets the company owns, and what sort of net earnings are being generated it's impossible to say what a $20k equity investment should get you in terms of ownership percentage. With that said, you want to look at a few to several years of books, look for trends. Some things to understand that might be subtle red flags: It's extremely common for early stage investors to essentially make loans rather than strictly buying shares. In the worst case scenario creditors get to participate in liquidation proceedings before shareholders do. You may be better off investing in this business via a loan that's convertible to equity at your discretion. Single owner service companies are difficult because all of the net earnings go to the proprietor and that person maintains all of the relationships. So taking something like 5 years of net earnings as the value of the company doesn't make much sense because you (or someone else) couldn't just step in and replace the owner. Granted, you aren't contemplating taking over the business, but it negates using an X years of net earnings valuation method. When you read about valuation there is a sort of overriding assumption that no single person could topple the operation which couldn't be farther from the truth in single employee service companies. Additionally, understand that your investment in a single owner company hinges completely on one person's ability and willingness to work. It's really vital to understand the purpose of the funds. Someone will be hired? $20,000 couldn't be even six months of wages... Put things in to perspective with a pad, pen and calculator. Don't invest in the pipe dream of a friend of yours, and DEFINITELY don't hand this person the downpayment for their new house. The first rule of investing is \"\"don't lose money,\"\" this isn't emotional, this is a dollars and cents pragmatic process. Why does the business need this money? How will you be paid back? Personally, I think it would be more gratifying to put $20k in a blender and watch it blend, this is probably a horrible investment. The risk should just be left to credit card companies.\"", "title": "" }, { "docid": "117509", "text": "What kind of financial analysis would make you comfortable about this decision? The HELOC and ARM are the biggest red flags to me in your current situation. While I don't expect interest rates to skyrocket in the near future, they introduce an interest rate risk that is easy to get rid of. Getting rid of the HELOC and converting to a fixed mortgage would be my first priority. If you also want to upgrade to a new home at the same time (meaning buy a new home contingent on the sale of your first, paying off the HELOC and mortgage), that's fine, but make sure that you can comfortably afford the payment on a fixed-rate mortgage with at least 20% down. I would not take additional cash out of your equity just to save it. You're going to pay more in interest that you're going to get in savings. From there things get trickier. While many people would keep the first property on a mortgage and rent it out, I am not willing to be a landlord for a part-time job, especially when the interest on the mortgage gouges my return on the rent. PLus leverage increases the risks as well - all it takes is to go one or two months without rent and you can find yourself unable to make a mortgage payment, wrecking your credit and possibly risking foreclosure. So my options in order of precedence would be: At what point does it make sense to become a landlord? The complicated answer is when the benefits (rent, appreciation) relative to the costs (maintenance, interest, taxes, etc.) and risks (lost rent, bad renters, home value variance) give you a better return that you could find in investments of similar risk. The simple answer is when you can pay cash for it. That takes interest and lost rent out of the equation. Again, some are willing to take those risks and pay 20% down on rental property. Some are able to make it work. Some of those go broke or lose their properties. when calculating the 20% down of a new property, does that need to be liquid funds, or can that be based on the value of the home you are selling You can make the purchase of the new home contingent on the sale of the first if you need to get the equity out of it to make the 20%. Do NOT refinance the first just to pull out the equity to make a down payment. It's not worth the fees of a refinance.", "title": "" }, { "docid": "48569", "text": "Most businesses want to grow, and there are a variety of ways to raise the money needed to hire new employees and otherwise invest in the business to increase the rate of that growth. You as a stock holder should hope that management is choosing the least expensive option for growth. Some of the options are debt, selling equity to venture capitalists, or selling equity on the open market (going public). If they choose debt, they pay interest on that debt. If they choose to sell equity to venture capitalists, then your shares get diluted, but hopefully the growth makes up for some of that dilution. If they choose to go public, dilution is still a concern, but the terms are usually a little more favorable for the company selling because the market is so liquid. In the US, current regulations for publicly traded companies cost somewhere in the neighborhood of $1M/year, so that's the rule of thumb for considering whether going public makes sense when calculating the cost of fundraising, but as mentioned, regulations make it less advantageous for executives who choose to sell their shares after the company goes public. (They can't sell when good spot prices appear.) Going public is often considered the next step for a company that has grown past the initial venture funding phase, but if cash-flow is good, plenty of companies decide to just reinvest profits and skip the equity markets altogether.", "title": "" }, { "docid": "538518", "text": "\"I am not familiar with this broker, but I believe this is what is going on: When entering combination orders (in this case the purchase of stocks and the writing of a call), it does not make sense to set a limit price on the two \"\"legs\"\" of the order separately. In that case it may be possible that one order gets executed, but the other not, for example. Instead you can specify the total amount you are willing to pay (net debit) or receive (net credit) per item. For this particular choice of a \"\"buy and write\"\" strategy, a net credit does not make sense as JoeTaxpayer has explained. Hence if you would choose this option, the order would never get executed. For some combinations of options it does make sense however. It is perhaps also good to see where the max gain numbers come from. In the first case, the gain would be maximal if the stock rises to the strike of the call or higher. In that case you would be payed out $2,50 * 100 = $250, but you have paid $1,41100 for the combination, hence this leaves a profit of $109 (disregarding transaction fees). In the other case you would have been paid $1,41 for the position. Hence in that case the total profit would be ($1,41+$2,50)100 = $391. But as said, such an order would not be executed. By the way, note that in your screenshot the bid is at 0, so writing a call would not earn you anything at all.\"", "title": "" }, { "docid": "177528", "text": "Founder makes available 100% equity, but uses a reasonable amount of the proceeds to pay him/herself a salary (or wage) and from that salary invests in the same initial offering to acquire shares for him/herself. I see several problems. What is a reasonable salary? Also, this leaves the door open to the following scam: Founders say that they are going to follow this plan. However, instead of buying shares, they simply quit after being paid the salary. They use knowledge gained from this business to start a competitor. Investors are left holding an empty company. Tax consequences. The founder would pay income tax on the salary. By contrast, if the founder instead sells shares, that would be capital gains tax, which is lower in many countries (e.g. the United States). Why would I want to invest in a business where the founders don't believe in it enough to take a significant equity stake? Consider the Amazon.com example. Jeff Bezos makes a minimal salary, around $80,000 a year, less than many of his employees. But he has a substantial ownership position. If the company doesn't make money, he won't. Would investors really value the stocks with a P/E of 232.10 in 2016 if they didn't trust him to make the right long term decisions? It's also worth noting that most initial public offerings (IPOs) are not made when the founder is the only employee. A single employee company instead looks for private investors, often called angel investors. Companies generally don't go public until they are established in some way, often making money. Negotiating with angel investors is different from negotiating with the public. They can personally review the books and once invested tend to have input on how the money is spent. In other words, this is mostly solving the wrong problem if you talk about IPOs. This might make more sense with a crowdfunded venture, as that replaces a few angel investors with many individuals. But most crowdfunded ventures tend to approach things from the opposite direction. Instead of looking for investors, they look for customers. If they offer a useful product, they will get customers. If not, they never get the money. Beyond all this, if a founder is only going to get a fair salary some of the time, then why put in any sweat equity? This works fine if the company looks valuable after a year. What if it doesn't? The founder is out a year of sweat equity and has nothing in return. That happens now too, but the possibility of the big return offsets it. You're taking out the big return. I don't think that this is good for either founders or investors. The founder trades a potentially good or even great return for a mediocre return. The investors trade a situation where both they and the founder benefit from a successful company to one where they benefit a lot more than the founder. That's not good for either side.", "title": "" }, { "docid": "288701", "text": "Yes, there are times when co-signing is the right choice. One is when you know more about the person than the loan issuer does. Consider a young person who has just started working in a volatile field, the kind of job where you can be told on Friday that you only get one shift next week but things might pick up the week after, and who makes maybe $12 an hour in that job. You've done the math and with 40 hour weeks they can easily afford the loan. Furthermore, you know this person well and you know that after a few weeks of not enough shifts, they've got the gumption to go out and find a second job or a different job that will give them 40 hours or more a week. And you know that they have some savings they could use to ensure that no payments will be missed even on low-wage weeks. You can cosign for this person, say for a car loan to get them a car they can drive to that job, knowing that they aren't going to walk away and just stop making the payments. The loan issuer doesn't know any of that. Or consider a young person with poor credit but good income who has recently decided to get smart about money, has written out a budget and a plan to rehabilitate their credit, and who you know will work passionately to make every payment and get the credit score up to a place where they can buy a house or whatever their goal is. Again, you can cosign for this person to make that happen, because you know something the lender doesn't. Or consider a middle aged person who's had some very hard knocks: laid off in a plant closing perhaps, marriage failure, lost all their house equity when the market collapsed, that sort of thing. They have a chance to start over again somewhere else and you have a chance to help. Again you know this isn't someone who is going to mismanage their money and walk away from the payments and leave you holding the bag. If you would give the person the money anyway (say, a car for your newly graduated child) then cosigning instead gives them more of a sense of accomplishment, since they paid for it, and gives them a great credit rating too. If you would not give the person the entire loan amount, but would make their payments for many months or even a year (say, your brother's mortgage for the house where he lives with a sick wife and 3 small children), then cosigning is only making official what you would have done anyway. Arrange with the borrower that if they can't make their payments any more, you will backstop them AND the item (car, house, whatever) is going up for sale to cover your losses. If you don't think you could enforce that just from the strength of the relationship, reconsider co-signing. Then sign what you need to sign and step away from it. It's their loan, not yours. You want them to pay it and to manage it and to leave you out of it until it's all paid off and they thank you for your help. If things go south, you will have to pay, and it may take a while for you to sell the item or otherwise stop the paying, so you do need to be very confident that the borrower is going to make every single payment on time. My point is just that you can have that confidence, based on personal knowledge of character, employment situation, savings and other resources, in a way that a lender really cannot.", "title": "" }, { "docid": "273187", "text": "why does it make sense financially to buy property and become a landlord? Because then your investment generates cash instead of just sitting idle. All taxes, fees and repairs aside it would take almost 21 years before I start making profits. No - your profit will be the rents that you collect (minus expenses). You still have an asset that is worth roughly what you paid for it (and might go up in value), so you don't need to recoup the entire cost of the property before making a profit. Compared to investing the same 150k in an ETF portfolio with conservative 4% in annual returns I would have made around 140k € after taxes in the same 21 years i.e. almost doubled the money. If you charge 600 € / month (and never miss a month of rental income), after 21 years you have made 151k € in rents plus you still have a property. That property is most likely going to be worth more than you paid for it, so you should have at least 300k € in assets. Having said all that, it does NOT always make sense to invest in rental property. Being a landlord can be a hard job, and there are many risks involved that are different that risks in financial investments.", "title": "" }, { "docid": "446652", "text": "I think I understand what I am doing wrong. To provide some clarity, I am trying to determine what the value of a project is to a firm. To do this I am taking FCF, not including interest or principal payments, and discounting back to get an NPV enterprise value. I then back off net debt to get to equity value. I believe what I am doing wrong is that I show that initial $50M as a cash outflow in period 0 and then back it off again when I go from enterprise value to equity value. Does this make any sense? Thanks for your help.", "title": "" }, { "docid": "392741", "text": "\"Someone's (or, a bank's) \"\"exposure to equities\"\" refers to the amount of value which has a risk that fluctuates with the equities market (ie: the stock market). In very broad terms, I think it might make sense to say that exposure to equities could mean, for example, owning many rental properties, if the rental market was \"\"highly correlated\"\" with the equities market. That is - if house prices go down when the equities market goes down, and if that relationship is very strong, then owning a house means you are exposed to the equities market. However, in the sense it is used there, it seems to mean direct exposure to equities - ie: owning stocks and stock-based funds.\"", "title": "" }, { "docid": "569490", "text": "> K-12 teachers never make six figure sums. In the U.S. that seems true. I found [this from 2012](http://money.usnews.com/careers/best-jobs/high-school-teacher/salary) that puts the median high-school teacher's salary at $55,050, with the top ten percent making about $85k. (By the way, this [OECD chart from 2013](http://educationbythenumbers.org/content/us-teachers-6th-highest-paid-world_982/) shows that the U.S. ranks 6th in the world in pay for primary-school teachers. I was surprised when I found this out.) > Professors in universities sometimes do, but for every professor that makes a lot of money there are probably dozens of untenured faculty who are barely making enough to feed themselves and put gas in their cars. You may be interested in [this chart from 2011](http://chronicle.com/article/Average-Faculty-Salaries-by/126586/) that gives salaries for professors, associate professors, assistant professors, new assistant professors, and instructors--all broken down by field. The data are only for four-year colleges and universities, though; that excludes community colleges, but I'm not sure whether it includes business schools, medical schools, or other graduate institutions. Not surprisingly, law and engineering are the most lucrative fields. > The real reason the big corporate interests want to privatize US education is to use all those jobs as bargaining chips in globalization. Interesting. Can you explain how this is intended to work? And if it would make sense for American corporations to do this, would it make sense for corporations from other countries to do it too? Are they doing it? I don't know anything about GATS or TiSA. Edit: grammar", "title": "" }, { "docid": "104485", "text": "If you have a new company and you want to attract investors, such as venture capitalists and private equity, incorporating in Delaware LLC probably makes sense. There are actually many investors who will only invest in a Delaware Online incorporation, so starting off by creating a Delaware corporation from the beginning may save a lot of money and stress down the road. You can also choose to form an LLC in Delaware, to begin with, then convert it to a C corporation later.", "title": "" }, { "docid": "23569", "text": "Does this make sense? Some corporate behemoth was making tons of money by selling disgusting sludge which I would not feed to a fucking dog, and because the true nature of this shit came to light, they lost a lot of business. They only had the business in the first place because people were unaware of what they were doing, and when the people learned, they were disgusted and tended to avoid it.", "title": "" }, { "docid": "65040", "text": "As the owner of the S-corp, it is far easier for you to move money in/out of the company as contributions and distributions rather than making loans to the company. Loans require interest payments, 1099-INT forms, and have tax consequences, whereas the distributions don't need to be reported because you pay taxes on net profits regardless of whether the money was distributed. If you were paid interest, disregard this answer. I don't know if or how you could re-categorize the loan once there's a 1099-INT involved. If no interest was ever paid, you just need to account for it properly: If the company didn't pay you any interest and never issued you a 1099-INT form (i.e. you wrote a check to the company, no promissory note, no tax forms, no payments, no interest, etc.) then you can categorize that money as a capital contribution. You can likewise take that money back out of the company as a capital distribution and neither of these events are taxable nor do they need to be reported to the IRS. In Quickbooks, create the following Equity accounts -- one for each shareholder making capital contributions and distributions: When putting money into the company, deposit into your corporate bank account and use the Capital Contribution equity account. When taking money out of the company, write yourself a check and use the Distributions account. At the end of every tax year, you can close out your Contributions and Distributions to Retained Earnings by making a general journal entry. For example, debit retained earnings and credit distributions on Dec 31 every year to zero-out the distributions account. For contributions, do the reverse and credit retained earnings. There are other ways of recording these transactions -- for example I think some people just use a Member Capital equity account instead of separate accounts for contributions and distributions -- and QB might warn you about posting journal entries to the special Retained Earnings account at the end of the year. In any case, this is how my CPA set up my books and it's been working well enough for many years. Still, never a bad idea to get a second opinion from your CPA. Be sure to pay yourself a reasonable salary, you can't get out of payroll taxes and just distribute profits -- that's a big red flag that can trigger an audit. If you're simply distributing back the money you already put into the company, that should be fine.", "title": "" }, { "docid": "475560", "text": "\"Recently, I asked about what the company valuation is and how many shares does my 4% represent.CFO told me that there is no point to talk about \"\"shares\"\" or \"\"stock\"\" since the company is not public. Is it right? No, it is wrong. Shares and stocks exist regardless of how they can be traded. Once a company is formed, there are stocks that belong to the owners in the proportion of the ownership. They may not exist physically, but they do exist on paper. As an owner of 5% of the company, you own 5% of the company stocks. I asked if my investor portion equity will be subjected under a vesting schedule, CFO said yes. That doesn't make sense to me, because I bought those 4%? Aren't those supposed to be fully vested? I agree to my employee equity to be vested. Doesn't make sense to me either, since your money is already in their pocket. But I'm not sure if its illegal. If that's what is written in the signed contract - then may be its possible to have that situation. But it doesn't make much sense, because these shares are granted to you in return to your money, not some potential future work (as the 1% employee's portion). You already gave the money, so why wouldn't they be vested? Best to read the contract upon which you gave them your money, I really hope you have at least that and not just gave them a check....\"", "title": "" } ]
5ab93444554299753720f797	Bob and wheel is the common name for a metrical device most famously used by the poet whose body of work includes some of the most well-regarded poetry written in what?	[ { "docid": "7219007", "text": "Bob and wheel is the common name for a metrical device most famously used by the Pearl Poet in \"Sir Gawain and the Green Knight\". The feature is found mainly in Middle English and Middle Scots poetry, where the bob and wheel occur typically at the end of a stanza. The \"bob\" is a very short line, sometimes of only two syllables, followed by the \"wheel\", longer lines with internal rhyme. There are at least forty known examples of bob and wheel use, but the origin of the form is obscure. It seems to predate the Pearl Poet. Bob and wheel is not used often in modern poetry.", "title": "" }, { "docid": "420961", "text": "The \"Pearl Poet\", or the \"Gawain Poet\", is the name given to the author of \"Pearl\", an alliterative poem written in 14th-century Middle English. Its author appears also to have written the poems \"Sir Gawain and the Green Knight\", \"Patience\", and \"Cleanness\"; some scholars suggest the author may also have composed \"Saint Erkenwald\". Save for the last (found in BL-MS \"Harley 2250\"), all these works are known from a single surviving manuscript, the British Library holding \"Cotton Nero A.x\". This body of work includes some of the most well-regarded poetry written in Middle English.", "title": "" } ]	[ { "docid": "6270699", "text": "The poetry of Gaius Valerius Catullus was written towards the end of the Roman Republic. It describes the lifestyle of the poet and his friends, as well as, most famously, his love for the woman he calls Lesbia.", "title": "" }, { "docid": "348345", "text": "Peter John Sinfield (born 27 December 1943) is an English poet and songwriter, most famously known as the lyricist and co-founder member of early incarnations of King Crimson, whose debut album \"In the Court of the Crimson King\" is regarded by some critics as one of the most influential progressive rock albums released.", "title": "" }, { "docid": "242281", "text": "In prosody, alliterative verse is a form of verse that uses alliteration as the principal ornamental device to help indicate the underlying metrical structure, as opposed to other devices such as rhyme. The most commonly studied traditions of alliterative verse are those found in the oldest literature of the Germanic languages, where scholars use the term 'alliterative poetry' rather broadly to indicate a tradition which not only shares alliteration as its primary ornament but also certain metrical characteristics. The Old English epic \"Beowulf\", as well as most other Old English poetry, the Old High German \"Muspilli\", the Old Saxon \"Heliand\", the Old Norse \"Poetic Edda\", and many Middle English poems such as \"Piers Plowman\", \"Sir Gawain and the Green Knight\", and the \"Alliterative Morte Arthur\" all use alliterative verse.", "title": "" }, { "docid": "968302", "text": "Gwen Harwood AO (8 June 19204 December 1995), née Gwendoline Nessie Foster, was an Australian poet and librettist. Gwen Harwood is regarded as one of Australia's finest poets, publishing over 420 works, including 386 poems and 13 librettos. She won numerous poetry awards and prizes, and one of Australia's most significant poetry prizes, the Gwen Harwood Poetry Prize is named for her. Her work is commonly studied in schools and university courses.", "title": "" }, { "docid": "2245362", "text": "Sima Xiangru ( , ; c. 179117BC) was an ancient Chinese poet, writer, musician, and official who lived during the Western Han Dynasty. Sima is a significant figure in the history of Classical Chinese poetry, and is generally regarded as the greatest of all composers of Chinese \"fu\" rhapsodies. His poetry includes his invention or at least development of the \"fu\" form, applying new metrical rhythms to the lines of poetry, which he mixed with lines of prose, and provided with several of what would in ensuing centuries become among a group of common set topics for this genre. He was also versatile enough to write in the \"Chu ci\" style, while it was enjoying a renaissance, and he also wrote lyrics in what would become known as the \"yuefu\" formal style.", "title": "" }, { "docid": "5915679", "text": "Malaipatukatam, (Tamil: மலைபடுகடாம்) is a Tamil poetic work in the \"Pathinenmaelkanakku\" anthology of Tamil literature, belonging to the Sangam period corresponding to between 100 BCE – 100 CE. \"Malaipatukatam\" contains 583 lines of poetry in the \"Achiriyappa\" meter. The poems were written by the poet Perunkosikanaar from Perunkunrur. In praise of a minor chieftain named Nannan Venmaan. \"Malaipatukatam\" belongs to the Pattupattu collection and follows the \"Arruppadtai\" style, a device used by most of the books in the Pattupattu collection.", "title": "" }, { "docid": "1618221", "text": "A tilting three-wheeler is a three-wheeled vehicle whose body and or wheels tilt in the direction of the turn. It is the most common leaning multi-wheeler type. Such vehicles can corner safely and comfortably despite having a narrow track. Some models are, unlike single-track vehicles such as two-wheeled bicycles and motorcycles, suitable for a year-round utilization time.", "title": "" }, { "docid": "51924446", "text": "Nontsizi Mgqwetho was a South African poet who is widely regarded as \"the first and only female poet to have written a substantial body of poetry in isiXhosa\". She is well known for her poetry which was published on Umteteli wa Bantu, a multilingual weekly Johannesburg newspaper, from 23 October 1920 until 5 January 1929. The poet's body of work from this period has cemented her place as one of the greatest literary artists ever to write in isiXhosa. Her poetry has been described as swaggering, urgent, confrontational and said to reveal more about the identity and struggles of an urban Christian black woman from the 19th century than other texts of that era.", "title": "" }, { "docid": "20502020", "text": "Percy Bysshe Shelley ( ; 4 August 17928 July 1822) was one of the major English Romantic poets, and is regarded by some as among the finest lyric poets in the English language, and one of the most influential. A radical in his poetry as well as in his political and social views, Shelley did not see fame during his lifetime, but recognition for his poetry grew steadily following his death. Shelley was a key member of a close circle of visionary poets and writers that included Lord Byron, Leigh Hunt, Thomas Love Peacock, and his own second wife, Mary Shelley, the author of \"Frankenstein\".", "title": "" }, { "docid": "38670628", "text": "Mohlaroyim (Uzbek: \"Mohlaroyim, Моҳларойим\" ) (1792–1842), most commonly known by her pen name Nodira, was an Uzbek poet and stateswoman. Nodira is generally regarded as one of the most outstanding Uzbek poets. She wrote poetry both in Uzbek and Persian. Nodira also used other pennames, such as Komila and Maknuna. Many of her diwans have survived. These diwans consist of more than 10,000 lines of poetry.", "title": "" }, { "docid": "5916016", "text": "Cirupanarruppatai,(Tamil:சிறுபாணாற்றுப்படை) is a Tamil poetic work in the \"Pathinenmaelkanakku\" anthology of Tamil literature, belonging to the Sangam period corresponding to between 100 BCE – 100 CE. \"Cirupanarruppatai\" contains 269 lines of poetry in the \"Achiriyappa\" meter. The poems were written by the poet Nathattanaar in praise of a minor Velir chieftain named Nalliyakkotan, a Nāka king of Nāka Nadu (ancient Malabar North Ceylon). \"Cirupanarruppatai\" belongs to the Pattupattu collection and follows the \"Arruppadtai\" style, a device used by most of the books in the Pattupattu collection.", "title": "" }, { "docid": "2760573", "text": "Martin Wylde Carter (7 June 1927 – 13 December 1997) was a Guyanese poet and political activist. Widely regarded as the greatest Guyanese poet, and one of the most important poets of the Caribbean region, Carter is best known for his poems of protest, resistance and revolution. Carter played an active role in Guyanese politics, particularly in the years leading up Independence in 1966 and those following immediately after. He was famously imprisoned by the British government in Guyana (then British Guiana) in October 1953 under allegations of \"spreading dissension\", and again in June 1954 for taking part in a PPP procession. Shortly after being released from prison the first time, Carter published his most well-known poetry collection, \"Poems of Resistance from British Guiana\" (1954).", "title": "" }, { "docid": "26379223", "text": "Pamela Harrison is an American poet and educator. She is the author of six poetry collections, most recently, \"What to Make of It\" (Turning Point, 2012). Her poems have been published in literary journals and magazines including \"Poetry, Beloit Poetry Journal, Georgia Review, Green Mountains Review, Cimarron Review,\" and \"Yankee Magazine.\" Her honors include fellowships from the MacDowell Colony and the Vermont Studio Center, as well as the PEN Northern New England Discovery Poet Award.", "title": "" }, { "docid": "13920759", "text": "The Concord Poetry Center is a non-profit organization founded in March, 2004, by poet and critic Joan Houlihan. Located at the Emerson Umbrella Center for the Arts, in Concord, Massachusetts, the Concord Poetry Center was established as an independent (non-university affiliated) organization in MetroWest and the Greater Boston area with an exclusive emphasis on activities and services for poets and lovers of poetry. Members have use of a library of journals, access to the poetry room, discount for classes, membership in an online discussion list, and participation in member readings. The center holds lectures, tributes, panel discussions and public readings by some of the most renowned poets of our time, including former and current Poet Laureate Robert Pinsky, current Poet Laureate Donald Hall, and Pulitzer Prize winner Franz Wright as well as many area poets. The center's programs and activities take place in the fall and spring and include workshops, seminars, online courses, and community-based readings.", "title": "" }, { "docid": "3165928", "text": "Golden Age of Russian Poetry is the name traditionally applied by Russian philologists to the first half of the 19th century. It is also called the Age of Pushkin, after its most significant poet (in Nabokov's words, the greatest poet this world was blessed with since the time of Shakespeare). Mikhail Lermontov and Fyodor Tyutchev are generally regarded as two most important Romantic poets after Pushkin. Vasily Zhukovsky and Konstantin Batyushkov are the best regarded of his precursors. Pushkin himself, however, considered Evgeny Baratynsky to be the finest poet of his day.", "title": "" }, { "docid": "265893", "text": "Blank verse is poetry written with regular metrical but unrhymed lines, almost always in iambic pentameter. It has been described as \"probably the most common and influential form that English poetry has taken since the 16th century\", and Paul Fussell has estimated that \"about three quarters of all English poetry is in blank verse\".", "title": "" }, { "docid": "37572010", "text": "Yerba buena or hierba buena is the Spanish name for a number of aromatic plants, most of which belong to the mint family. \"Yerba buena\" translates as \"good herb\". The specific plant species regarded as \"yerba buena\" varies from region to region, depending on what grows wild in the surrounding landscape, or which species is customarily grown in local gardens. Perhaps the most common variation of this plant is spearmint (\"Mentha spicata\"). The term has been (and is currently) used to cover a number of aromatic true mints and mint relatives of the genera \"Clinopodium\", \"Satureja\" or \"Micromeria\". All plants so named have medicinal properties, and some have culinary value as herbal teas or seasonings as well.", "title": "" }, { "docid": "1574284", "text": "Susanne Antonetta is the pen name of Suzanne Paola (born 1956, in Georgia), an American poet and author who is most widely known for her book \"Body Toxic: An Environmental Memoir\" (ISBN ). In 2001, \"Body Toxic\" received recognition as a 'Notable Book' from the New York Times. An excerpt of \"Body Toxic\" was published as a stand-alone essay which was recognized as a 'Notable Essay' in the 1998 Best American Essays 1998 anthology. She has published several prize-winning collections of poems, including \"Bardo\", a Brittingham Prize in Poetry winner, and the poetry books \"Petitioner\", \"Glass\", and most recently \"The Lives of The Saints\". She currently resides in Washington with her husband and adopted son. She is widely published both in newspapers such as \"The New York Times\" and \"The Washington Post\", as well as in literary journals including \"Orion\", \"Brevity\", \"JuxtaProse Literary Magazine\", \"Seneca Review\", and \"Image\". She is the current Editor-in-Chief of \"Bellingham Review\".", "title": "" }, { "docid": "39783343", "text": "Klecksography is the art of making images from inkblots. The work was pioneered by Justinus Kerner, who included klecksographs in his books of poetry. Since the 1890s, psychologists have used it as a tool for studying the subconscious, most famously Hermann Rorschach in his Rorschach inkblot test.", "title": "" }, { "docid": "2467043", "text": "Ibn al-Farid or Ibn Farid; Arabic, عمر بن علي بن الفارض (`Umar ibn `Alī ibn al-Fārid) (22 March 1181–1234) was an Arab poet. His name literally means “son of the legal advocate for women”, and his father was well regarded for his work in the legal sphere. He was born in Cairo from a Syrian parents came from Hama in Syria , lived for some time in Mecca and died in Cairo. His poetry is entirely Sufic, and he was esteemed the greatest mystic poet of the Arabs. Some of his poems are said to have been written in ecstasies.", "title": "" }, { "docid": "228774", "text": "Heptameter is a type of meter where each line of verse contains seven metrical feet. It was used frequently in Classical prosody, and in English, the line was used frequently in narrative poetry since the Romantics. The meter is also called septenary, and this is the most common form for medieval Latin and vernacular verse, including the \"Ormulum\". Its first use in English is possibly the \"Poema Morale\" of the twelfth/thirteenth century.", "title": "" }, { "docid": "50515207", "text": "A philosophical poet is an author or scholar who employs poetic devices, styles, or forms to explore subjects common to the field of philosophy. Their writing often addresses questions related to the meaning of life, the nature of being (ontology), theories of knowledge and knowing (epistemology), principles of beauty (aesthetics), first principles of things (metaphysics) or the existence of God. Some may make broad philosophical inquires and engage with diverse philosophical topics throughout their poetry, while others may concentrate within one branch of philosophical poetry. For example, Dante is considered by some to be both a philosophical poet, in a general sense, as well as a metaphysical poet.", "title": "" }, { "docid": "15143184", "text": "The Early fuel evaporator is a device found in some internal combustion engines with carburetors. It can sometimes be referred to as an Electronic fuel evaporator. The device on a car, commonly referred to as an EFE heater is located between the throttle body of the carburetor and the intake manifold as a gasket and contains a resistance grid that heats the air/fuel mixture. The purpose of the EFE heater is to aid with vaporization of fuel in cold conditions, as well as to reduce exhaust emissions by running for about two minutes to allow for leaner choke calibrations. Photo shown below is of a USED, most likely defective, EFE Grid Gasket. Most common manufacture was Sylvania. Sylvania model 515853 is used on the 84 Buick Century Limited 3.0L 2 Barrel gas engine.", "title": "" }, { "docid": "8946189", "text": "A smoking pipe is a device made to allow the user to inhale or taste smoke or vapor derived from the burning or vaporization of some substance. The most common form of these is the tobacco pipe, which is designed for use with tobacco, although the device itself may be used with many other substances. The pipes are manufactured with a variety of materials, the most common (as the popularity of its use): Briar, Heather, corn, meerschaum, clay, cherry, glass, porcelain, ebonite, acrylic and other more unusual materials. Other kinds of smoking pipes include:", "title": "" }, { "docid": "40415411", "text": "The Phoenix Living Poets was a series of slim books of poetry published from 1960 until 1983 by Chatto and Windus Ltd. The poets included in the series offer a cross-section of poets of the era, including some notable writers. Generally those writing were not producing the most experimental work of the era but, taken as a whole, the series covers a significant range of voices and styles.", "title": "" }, { "docid": "10744564", "text": "Yolande Cornelia \"Nikki\" Giovanni, Jr. (born June 7, 1943) is an American poet, writer, commentator, activist, and educator. One of the world's most well-known African-American poets, her work includes poetry anthologies, poetry recordings, and nonfiction essays, and covers topics ranging from race and social issues to children's literature. She has won numerous awards, including the Langston Hughes Medal, the NAACP Image Award. She has been nominated for a Grammy Award, for her album \"The Nikki Giovanni Poetry Collection\". Additionally, she has recently been named as one of Oprah Winfrey’s 25 \"Living Legends\" (29).", "title": "" }, { "docid": "18561705", "text": "Marc Kaminsky is a poet, writer, psychotherapist, and gerontologist whose work ranges from editing a study of life review called \"The Uses of Reminiscence\" to poetry like \"A Table With People\" and \"The Road from Hiroshima\". He organized and conducted among the earliest writing and reminiscing groups for elders. He also did work on the culture of Yiddishkeit. He edited the work of Barbara Meyerhoff in \"Stories As Equipment for Living\". His long poem, \"The Road from Hiroshima\", was produced as a play for voices for National Public Radio and was the inspiration for other works including a musical requiem. His most recent book is \"Shadow Traffic\", a collection of essays, poems and short stories that deals with the aftermath of the Holocaust as well as the aftermath of personal traumas.", "title": "" }, { "docid": "25288890", "text": "An isometric exercise tool is a device used to exercise most body parts including the wrist and is often used as part of physical therapy or in order to build muscle strength in a low impact manner. Devices can range in size from large bulky machines used by physicians to small hand-held devices that can be used by an individual. Isometric devices have been used for centuries. The first devices did not display the users' output; nowadays there are devices that can digitally output the users force. Before that some devices used an analog format.", "title": "" }, { "docid": "53481", "text": "A game of chance is a game whose outcome is strongly influenced by some randomizing device, and upon which contestants may choose to wager money or anything of monetary value. Common devices used include dice, spinning tops, playing cards, roulette wheels, or numbered balls drawn from a container. A game of chance may have some skill element to it, however, chance generally plays a greater role in determining the outcome than skill. A game of skill, on the other hand, also has an element of chance, but with skill playing a greater role in determining the outcome.", "title": "" }, { "docid": "15600", "text": "James Augustine Aloysius Joyce (2 February 1882 – 13 January 1941) was an Irish novelist, short story writer, and poet. He contributed to the modernist avant-garde and is regarded as one of the most influential and important authors of the 20th century. Joyce is best known for \"Ulysses\" (1922), a landmark work in which the episodes of Homer's \"Odyssey\" are paralleled in a variety of literary styles, perhaps most prominently stream of consciousness. Other well-known works are the short-story collection \"Dubliners\" (1914), and the novels \"A Portrait of the Artist as a Young Man\" (1916) and \"Finnegans Wake\" (1939). His other writings include three books of poetry, a play, his published letters and occasional journalism.", "title": "" } ]
3157	What tax advantage should I keep an eye for if I am going to relocate?	[ { "docid": "15844", "text": "\"Look for states that have no income tax. A lot of these states supplement their revenue with higher property taxes, but if you rent and do not own property in the state, then you will have no state tax liability. Similarly, many states treat capital gains no differently than income tax, so if you make your earnings due to a large nest egg, then way you will still incur no tax liability on the state level Look for \"\"unincorporated\"\" areas, as these are administrative divisions of states that do not have a municipal government, and as such do not collect local taxes. Look for economic development perks of the new jurisdiction. Many states have some kind of formal tax credit for people that start business or buy in certain areas, but MONEY TALKS and you can make an individual arrangement with any agency, municipality etc. If the secretary at city hall doesn't know about a prepackaged formal arrangement that is offered to citizens, then ask for the \"\"expedited development package\"\" which generally has a \"\"processing fee\"\" involved. This is something you make up ie. \"\"What is the processing fee for the expedited development package, quote on quote\"\" States like Maryland and Nevada have formalized this process, but you are generally paying off the Secretary of State for favorable treatment. You'll always be paying off someone.\"", "title": "" }, { "docid": "182217", "text": "\"Depends. If you can choose where to relocate to, then I second the \"\"no income tax\"\" states. But even of these chose wisely, some have no income taxes at all, others have taxes on some kinds of income. Some don't have neither individual nor corporate taxes, some tax businesses in some ways. Some compensate with higher property taxes, others compensate with higher sales taxes. On the other hand, you might prefer states with income taxes but no sales taxes. It can happen if your current income is going to be low, but you'll be spending your savings. If you don't have a choice (for example, your employer wants you to move closer to their office), then you're more limited. Still, you can use the tax break on moving expenses (read the fine print, there are certain employment requirements), and play with the state taxes (if you're moving to a state with less/no taxes - move earlier, if its the other way - move later). Check out for cities that have income taxes. In some states it cannot happen by law (for example, in California only the state is allowed to collect income taxes), in others it is very common (Ohio comes to mind). Many things to consider in New York. New York City has its own income tax (as well as Yonkers, as far as I remember these are the only ones in the State of New York). So if you want to save on taxes in NYS but live close to the city, consider White Plains etc. If you work in NYC its moot, you're going to pay city taxes anyway. That is also true if you live in NJ but work in the city, so tax-wise it may be more efficient not to live across state lines from your place of work.\"", "title": "" } ]	[ { "docid": "317386", "text": "It's also bad to create skewed incentives that result in the best candidate not getting the job. Or should we have no feelings for the other candidates who apply? Edit: Hypothetical situation. My wife gets a job in another city, and I also need to relocate. I currently have a job. I am the best candidate for a new job, but don't get it because of the proposed tax credit. Not only have you created an incentive for the company to hire a second best candidate, which is bad for the company and its customers, but I am unable to relocate. Bad policy. Economic engineering that sounds good, but is not the most efficient means of allocating resources.", "title": "" }, { "docid": "409854", "text": "\"You may want to hold onto the $5000 and keep it in savings. Interest rates are for crap, even in \"\"high yield\"\" accounts, so you can rightly not consider it investing. You should be graduating college soon. It would suck if an emergency crops up to prevent you from graduating. I assume that you are going into a high paying career given your nice income from internships. Your best investment is yourself at this point. Completing your education, and obtaining your degree trumps all. You could use that extra 5000 as a hedge/insurance policy/emergency fund to help insure you graduate. Also you are likely to have some moving expenses once you graduate. That 5K could be used to help cover those costs. The worst case is you graduate with no emergencies, you get a nice signing bonus and relocation package, and you still have the $5000. Well you still have until 15 April 2015 to put money in your ROTH for 2014. This holds true for every tax year. Given your current financial status, you are likely to find yourself soon contributing the max to your 401K and ROTH. Once that happens, money beyond that can be invested into mutual funds stocks that are not tax advantaged, real estate, or some other choices. Well then you have some things to think about.\"", "title": "" }, { "docid": "271415", "text": "As an NRI, you can't hold a regular savings account. It should have been converted to NRO. Option 1: Open NRE account : Since I am relocating permanently this might not be good option for me as converting This is the best Option as funds into NRE are not taxable in India. The provides a clean paper trail so that if there are any tax queries, you can answer them easily. You can open a Rupee NRE account, move the funds. On return move the funds into Normal Savings account and close the NRE account. This is not much of hassle. Option 2: Create NRO account: There would be taxes on the interest earned of the funds. But I am not sure of this, since I will have been moved to India permanently would I need to still pay taxes on the interest earned while I am in India? Any interest in NRO or normal savings account is taxable in India. There is no exemption. Option 3: I can transfer my funds directly to my account in India but I believe I would have to pay tax on the the funds that I transfer and that would be double taxation. Which I think would be the worst option for me. Please correct me if I am wrong. This is incorrect. Any earnings outside of India when your status is NRI, is not taxable in India. Opening an NRE account provides proper paper trail of funds. As an NRI one cannot hold normal savings account. This should have been converted into an NRO account. Although there is no penalty prescribed, its violation of FEMA regulation. I also hope you were declaring any income in India, i.e. interest etc on savings and filing returns accordingly. Option 4: I can transfer the funds to my direct relatives account. I still believe there would be tax to be paid on the interest earned of the amount. You can transfer it to your parents / siblings / etc. This would come under gift tax purview and would not be taxable. They can then gift this back to you. However such transactions would appear to be evading regulations and may come under scrutiny. Interest on Savings account is taxable. So best is go with Option 1. No hassle. Else go with Option 3, but ensure that you have all the paperwork kept handy for next 7 years.", "title": "" }, { "docid": "206313", "text": "I would say you should invest in the market that is more convenient for you, bearing in mind that if you buy ADRs you may have some things to keep an eye on depending on certain events as mentioned by duffbeer703. So, if you are investing with an account in the U.S., go with the ADRs as that will avoid some currency conversion hassles and possible exchange rate issues. I am not certain, but I have a feeling that would also make it easier for you to keep the taxman happy.", "title": "" }, { "docid": "131451", "text": "\"For example, for my employer I received a signing bonus, and a \"\"relocation lump sum\"\" separate from that signing bonus. The relocation lump sum is taxed and will appear as income on my W-2, and I can spend it on anything I want. That said, should the relocation lump sum count towards the entry quoted above in Form 3903, or would it be considered the same as any other bonus; thus allowing me to take a full deduction for all of my deductible travel expenses? The signing bonus and relocation lump sum will appear as regular income on your W-2. You can think of the relocation bonus as something to cover the pain and suffering the cost of moving, without needing to send in receipts. Lets assume that you meet the distance and time tests, so there is potential to save money on your taxes. Lets also put your actual moving expenses as $2500. If you have valid moving expenses the IRS will allow you to use them to reduce your AGI. So now you can reduce your AGI by the $2500. Enter the total amount your employer paid you for the expenses listed on lines 1 and 2 that is not included in box 1 of your Form W-2 (wages). This amount should be shown in box 12 of your Form W-2 with code P. My question is: what exact payments from your employer should be entered here? I realize that you can just write the number you get in box 12 with code P on your W-2, but I'm curious how they come up with this number. In some cases the company will reimburse you your moving expenses up to a maximum of $x. For example a maximum of $1000 That means you submit receipts for those expenses and they give you a check or add it to your next paycheck. The check will either be for the amount on your receipts or the maximum amount, whichever is smaller. In this situation with actual expenses of $2500 and a reimbursement of $1000 you can reduce your AGI by $1500.\"", "title": "" }, { "docid": "160340", "text": "\"If all of the relocation expenses are paid by your employer to the moving companies, then you should not have any tax liability for those payments. Relocation expenses should be treated as normal business expenses by your employer. Note I emphasize \"\"should\"\" because it's possible that your employer \"\"could\"\" consider it income to you, but companies generally do not go out of their way to classify normal business expenses as income since it costs both them and you more money in taxes. As a side note, the reason your company is paying these expenses directly is probably to lessen the likelihood of these expenses being questioned in an audit (in comparison to if they cut you a reimbursement check which could get more scrutiny).\"", "title": "" }, { "docid": "52538", "text": "Let's say I am able to pass the level 1 CFA exam, would this allow me to pursue a career within the finance world without needing to look into a second bachelor's in finance or an MBA-finance? I know this is a long road ahead and one that will be full of difficult times. Yeah, my focus was school counseling. So this would allow me to graduate and look at a private practice license after I meet the hour requirements or give me the opportunity to become a school counselor as soon as I graduate. These positions don't pay the most but they are at least something. I live in a rural area currently but would be looking to relocate to Denver upon graduation. If I stopped the MS degree then I would only have my BA in Psychology to fall back on until taking and passing the CFA. I'm not sure I could make as much with that degree while I attempt to transition careers. As far as the emotionally taxing aspect, working with children who come from broken homes all day, every day is extremely exhausting mentally and for someone like me it is difficult to leave work at work in this line. I become emotionally invested in the outcome of my work and have a hard time disconnecting and not caring when I am on my time. The main reason I am looking at switching into this type of career isn't based around the earning potential. Although this is an added benefit, the greatest reasoning is because a) this helping profession has left me burned out and I want to continue to help but in a less intimate way and b) my personality and strengths really fit with this type of career. I have had to work hard to develop as a counselor and I still struggle at times. I have a more concrete and factual mind and I process things in a critical and evaluative manner. Ideal for careers that require critical evaluation, behind the scenes work, and a love for working with numbers and data. I'll take a look at the WSO site and ask for some advice on there as well. The largest decision that I will need to make is if finishing the MS is going to be worth the 20k investment for one more year or if I should cut out and focus on developing a career in this field while working full-time and starting to pay off student loans. My student loan debt is unfortunately higher than I would like, but I come from a family of alcoholics, users, and I finished high school while living on friend's couches for the last two years - so it has been a necessary evil. Having to pay on the loans if I were to stop the MS is also a factor but I know there are income-driven repayment plans available that I can take advantage of if my earnings aren't as high as I would like. Thank you again for your time - it is greatly appreciated.", "title": "" }, { "docid": "96110", "text": "If you're sure you want to go the high risk route: You could consider hot stocks or even bonds for companies/countries with lower credit ratings and higher risk. I think an underrated cost of investing is the tax penalties that you pay when you win if you aren't using a tax advantaged account. For your speculating account, you might want to open a self-directed IRA so that you can get access to more of the high risk options that you crave without the tax liability if any of those have a big payout. You want your high-growth money to be in a Roth, because it would be a shame to strike it rich while you're young and then have to pay taxes on it when you're older. If you choose not to make these investments in a tax-advantaged account, try to hold your stocks for a year so you only get taxed at capital gains rates instead of as ordinary income. If you choose to work for a startup, buy your stock options as they vest so that if the company goes public or sells privately, you will have owned those stocks long enough to qualify for capital gains. If you want my actual advice about what I think you should do: I would increase your 401k percentage to at least 10% with or without a match, and keep that in low cost index funds while you're young, but moving some of those investments over to bonds as you get closer to retirement and your risk tolerance declines. Assuming you're not in the 25% tax bracket, all of your money should be in a Roth 401k or IRA because you can withdraw it without being taxed when you retire. The more money you put into those accounts now while you are young, the more time it all has to grow. The real risk of chasing the high-risk returns is that when you bet wrong it will set you back far enough that you will lose the advantage that comes from investing the money while you're young. You're going to have up and down years with your self-selected investments, why not just keep plugging money into the S&P which has its ups and downs, but has always trended up over time?", "title": "" }, { "docid": "417981", "text": "\"While the question is very localized, I'll answer about the general principle. My main question is with how far away it is (over 1000 miles), how do I quantify the travel expenses? Generally, \"\"necessary and ordinary\"\" expenses are deductible. This is true for business and also true for rentals. But what is necessary and what is ordinary? Is it ordinary that a landlord will manage the property 1000 miles away by himself on a daily basis? Is it ordinary for people to drive 1000 miles every week? I'd say \"\"no\"\" to both. I'd say it would be cheaper for you to hire a local property manager, thus the travel expense would not be necessary. I would say it would be cheaper to fly (although I don't know if its true to the specific situation of the OP, but as I said - its too localized to deal with) rather than drive from Texas to Colorado. If the OP thinks that driving a thousand miles is indeed ordinary and necessary he'll have to justify it to the IRS examiner, as I'm sure it will be examined. 2 trips to the property a year will be a nearly 100% write-off (2000 miles, hotels, etc). From what I understood (and that is what I've been told by my CPA), IRS generally allows 1 (one) trip per year per property. If there's an exceptional situation - be prepared to justify it. Also, keep all the receipts (like gas, hotel, etc.... If you claim mileage but in reality you took a flight - you'll get hit hard by the IRS when audited). Also while I'm up there am I allowed to mix business with pleasure? You cannot deduct personal (\"\"pleasure\"\") expenses, at all. If the trip is mainly business, but you go out at the evening instead of staying at the hotel - that's fine. But if the trip is \"\"business\"\" trip where you spend a couple of hours at your property and then go around having fun for two days - the whole trip may be disallowed. If there's a reasonable portion dedicated to your business/rental, and the rest is pleasure - you'll have to split some of the costs and only deduct the portion attributed to the business activities. You'll have to analyze your specific situation, and see where it falls. Don't stretch the limits too much, it will cost you more on the long run after all the audits and penalties. Can I also write off all travel involved in the purchase of the property? Although, again, the \"\"necessary and ordinary\"\" justification of such a trip is arguable, lets assume it is necessary and ordinary and generally justified. It is reasonable to expect you to go and see the property with your own eyes before the closing (IMHO, of course, I'm not an authority). Such an expense can be either business or investment expense. If its a business expense - its deductible on schedule C. If its an investment expense (if you do buy the property), its added to the cost of the property (capitalized). I'm not a tax adviser or a tax professional, and this is not a tax advice. This answer was not written or intended to be used, and cannot be used, for the purpose of avoiding any tax related penalties that may be imposed on you or any other person under the Internal Revenue Code. You should seek a professional consultation with a CPA/Attorney(tax) licensed in your State(s) or a Federally licensed Enrolled Agent (EA).\"", "title": "" }, { "docid": "589256", "text": "\"For some people, it should be a top priority. For others, there are higher priorities. What it should be for you depends on a number of things, including your overall financial situation (both your current finances and how stable you expect them to be over time), your level of financial \"\"education\"\", the costs of your mortgage, the alternative investments available to you, your investing goals, and your tolerance for risk. Your #1 priority should be to ensure that your basic needs (including making the required monthly payment on your mortgage) are met, both now and in the near future, which includes paying off high-interest (i.e. credit card) debt and building up an emergency fund in a savings or money-market account or some other low-risk and liquid account. If you haven't done those things, do not pass Go, do not collect $200, and do not consider making advance payments on your mortgage. Mason Wheeler's statements that the bank can't take your house if you've paid it off are correct, but it's going to be a long time till you get there and they can take it if you're partway to paying it off early and then something bad happens to you and you start missing payments. (If you're not underwater, you should be able to get some of your money back by selling - possibly at a loss - before it gets to the point of foreclosure, but you'll still have to move, which can be costly and unappealing.) So make sure you've got what you need to handle your basic needs even if you hit a rough patch, and make sure you're not financing the paying off of your house by taking a loan from Visa at 27% annually. Once you've gotten through all of those more-important things, you finally get to decide what else to invest your extra money in. Different investments will provide different rewards, both financial and emotional (and Mason Wheeler has clearly demonstrated that he gets a strong emotional payoff from not having a mortgage, which may or may not be how you feel about it). On the financial side of any potential investment, you'll want to consider things like the expected rate of return, the risk it carries (both on its own and whether it balances out or unbalances the overall risk profile of all your investments in total), its expected costs (including its - and your - tax rate and any preferred tax treatment), and any other potential factors (such as an employer match on 401(k) contributions, which are basically free money to you). Then you weigh the pros and cons (financial and emotional) of each option against your imperfect forecast of what the future holds, take your best guess, and then keep adjusting as you go through life and things change. But I want to come back to one of the factors I mentioned in the first paragraph. Which options you should even be considering is in part influenced by the degree to which you understand your finances and the wide variety of options available to you as well as all the subtleties of how different things can make them more or less advantageous than one another. The fact that you're posting this question here indicates that you're still early in the process of learning those things, and although it's great that you're educating yourself on them (and keep doing it!), it means that you're probably not ready to worry about some of the things other posters have talked about, such as Cost of Capital and ROI. So keep reading blog posts and articles online (there's no shortage of them), and keep developing your understanding of the options available to you and their pros and cons, and wait to tackle the full suite of investment options till you fully understand them. However, there's still the question of what to do between now and then. Paying the mortgage down isn't an unreasonable thing for you to do for now, since it's a guaranteed rate of return that also provides some degree of emotional payoff. But I'd say the higher priority should be getting money into a tax-advantaged retirement account (a 401(k)/403(b)/IRA), because the tax-advantaged growth of those accounts makes their long-term return far greater than whatever you're paying on your mortgage, and they provide more benefit (tax-advantaged growth) the earlier you invest in them, so doing that now instead of paying off the house quicker is probably going to be better for you financially, even if it doesn't provide the emotional payoff. If your employer will match your contributions into that account, then it's a no-brainer, but it's probably still a better idea than the mortgage unless the emotional payoff is very very important to you or unless you're nearing retirement age (so the tax-free growth period is small). If you're not sure what to invest in, just choose something that's broad-market and low-cost (total-market index funds are a great choice), and you can diversify into other things as you gain more savvy as an investor; what matters more is that you start investing in something now, not exactly what it is. Disclaimer: I'm not a personal advisor, and this does not constitute investing advice. Understand your choices and make your own decisions.\"", "title": "" }, { "docid": "537450", "text": "Fuck you. Fuck the HELL out of you. First, what if I operate a business that has industry-wise small margins? All manufacturing, for instance, operates on an average margin of 2%. How much is that tax increase going to be, again? 5%? Thanks, I guess you didn't want a manufacturing sector in the US after all. Second, what if my competitive advantage is a small margin? For many small businesses, that is their only competitive advantage in their start-up years. Third, when the HELL did being left alone and keeping the money I earned by generating wealth and providing services become a motherfucking SUBSIDY? When the hell did the money I earn become the government's by right???? Also fuck you, you disgusting self-important pimple. The risk-takers, wealth generators and employers of half of America are in fear for their survival; their livelyhoods, their life's work, and their retirement are all at risk from government meddling; and you cavalierly snark that they should just go out of business. May you live long enough to one day learn how it feels.", "title": "" }, { "docid": "594051", "text": "\"Good debt and \"\"Bad debt\"\" are just judgement calls. Each person has their own opinion on when it is acceptable to borrow money for something, and when it is not. For some, it is never acceptable to borrow money for something; they won't even borrow money to buy a house. Others, of course, are in debt up to their eyeballs. All debt costs money in interest. So when evaluating whether to borrow or not, you need to ask yourself, \"\"Is the benefit I am getting by borrowing this money worth the cost?\"\" Home ownership has a lot of advantages: For many, these advantages, coupled with the facts that home mortgages are available at extremely low interest rates and that home mortgage interest is tax-deductible (in the U.S.), make home mortgages \"\"worth it\"\" in the eyes of many. Contrast that with car ownership: For these reasons, there are many people who consider the idea of borrowing money to purchase a car a bad idea. I have written an answer on another question which outlines a few reasons why it is better to pay cash for a car.\"", "title": "" }, { "docid": "332278", "text": "One of the often cited advantages of ETFs is that they have a higher liquidity and that they can be traded at any time during the trading hours. On the other hand they are often proposed as a simple way to invest private funds for people that do not want to always keep an eye on the market, hence the intraday trading is mostly irrelevant for them. I am pretty sure that this is a subjective idea. The fact is you may buy GOOG, AAPL, F or whatever you wish(ETF as well, such as QQQ, SPY etc.) and keep them for a long time. In both cases, if you do not want to keep an on the market it is ok. Because, if you keep them it is called investment(the idea is collecting dividends etc.), if you are day trading then is it called speculation, because you main goal is to earn by buying and selling, of course you may loose as well. So, you do not care about dividends or owning some percent of the company. As, ETFs are derived instruments, their volatility depends on the volatility of the related shares. I'm wondering whether there are secondary effects that make the liquidity argument interesting for private investors, despite not using it themselves. What would these effects be and how do they impact when compared, for example, to mutual funds? Liquidity(ability to turn cash) could create high volatility which means high risk and high reward. From this point of view mutual funds are more safe. Because, money managers know how to diversify the total portfolio and manage income under any market conditions.", "title": "" }, { "docid": "317570", "text": "I see a couple of ways of getting at this. One would be to switch to a VAT. That would capture a good amount of revenue on anything that's made here. Second, I want IP to be taxed. We pay property taxes, so I think that trademarks and copyrighted works should be taxed just like how real property is taxed. You want to register the Burger King logo in the US? Sure thing! You will pay a percentage of its value every year and you get to use it exclusively with the full protection of the US courts your taxes help fund. I also see this as a good way out of the IP cesspool we're currently in. Copyright has become unreasonably long mostly because Disney doesn't want to lose the rights to Mickey Mouse. Look, I am sympathetic to Disney's argument. Mickey genuinely is important to them. But Mickey is fucking things up for everyone else. So I think Disney should pay a percentage of Mickey's value every year. In exchange, they keep their copyright forever as long as they keep paying. Now, if the copyright tax isn't paid, then the property becomes public domain forever. This would let Disney have what they want while non-profitable copyrights become public domain, as they should. Anyhow, the one thing all the big tax-avoiding companies have in common is IP. If you tax their IP in exchange for protection in US courts, there's really no way around that. They will either have to pay or let their IP go public domain.", "title": "" }, { "docid": "308208", "text": "So your accountant certainly knows much more than I do about Israeli tax law and its interactions with US tax law, which is zero. I'm going to look at this problem from the investment perspective which I hope to convince you is the most important place to start. Then you can adjust for interactions between the Isreali and US tax codes. Even if the tax breaks are exceptional, it would be hard to recommend buying real estate as an investment in the 7-10 year time frame. Especially if this real estate is in the US. Open/Closing fees, mortgage fees, risk of property devaluation, bad-renters, acts of god, insurance costs and tax complications make short to medium term investments in real estate a particularly risky way to invest. Buying a local apartment and renting is somewhat more reasonable as you don't have to worry about the currency conversion and you can do a lot more research in your local environment and keep a closer eye on the property, it is still this a pretty concentrated risk. Saving and investing using tax-advantaged accounts is generally considered a great way to build toward a down payment in the medium term. A mixture of mostly local bonds with some local and foreign stocks and more and more cash as it gets close to purchase time is generally what is recommended when saving for a home. This mixture is relatively safe and will tend to grow steadily without the concentrated risk of a real estate investment. PFIC rules are complicated and certainly worth taking some time to understand, but owning real estate especially in a foreign country seems much more complicated and certainly riskier. There may be some rule that makes investing in REITs much better than normal stocks in these particular accounts though I would be surprised if that were the case. It is generally not true for people under just he US tax code. So while option (1) may not be the absolute best from a tax perspective it would certainly be my guess as the most likely to succeed.", "title": "" }, { "docid": "12034", "text": "I assume I can/will need to file an 83(b) election, in order to avoid tax repercussions? What exactly will this save me from? 83(b) election is for restricted stock grants, not for stock purchases. For restricted stocks, you generally pay income tax when they vest. For startups the price difference between the time of the grant and the time of the vesting can be astronomical and by choosing 83(b) you effectively pay income tax on the value of the grant instead of the value of the vest. Then, you only pay capital gains tax on the difference between the sale price and the grant value when you sell. In your case you're exercising an option, i.e.: you're buying a stock, so 83(b) is irrelevant. What you will pay though is the tax on the difference between the strike price and the stock FMV (unless the stocks you end up buying are restricted - which would have been the case if you exercised your options early, but I don't think is going to be the case now). What steps should I take to (in the eyes of the law) guarantee that the board has received my execution notice? The secretary of the board is a notorious procrastinator and can be very unorganized. You should read what the grant contract/company policy says on that. Ask the HR/manager. Usually, a certified letter with return receipt should be enough, but you should verify the format, the address, and the timeframe.", "title": "" }, { "docid": "135017", "text": "\"You can hire a good CPA for a really low price. They can advise you on how to do exactly what you said and many other aspects of your business. Mine does this as a courtesy with the filing of my taxes. And the filing of my taxes is not all that much. It is great value for the money. Recently I had to make a decision that is a potential audit situation and can go badly if not properly documented. It was not hard to document (with the CPA's help), but now that it is so I don't lose mental energy on if I am going to get \"\"caught\"\" by the IRS. Let them come, I have the necessary documentation. Beyond the IRS, I really like the documentation that you are trying to put behind this loan. Having this in writing helps smooth this potentially bad situation between you and the BIL. I would go above and beyond writing conditions and contingencies down in order to keep this relationship happy. With these kinds of things, cover the applicable 5 \"\"Ds\"\" of partnership agreements: However, I would add another: Boom. What happens if your business takes off? Perhaps there should be a clause to retire the loan prior to you expanding beyond a certain level. Please understand I am not suggesting that any of these bad things are going to happen to you (except the Boom, I really hope that happens to you), but it is a way to communicate contingent actions if one of the risks of small business materializes. Having agreements ahead of time helps avoid crisis.\"", "title": "" }, { "docid": "308319", "text": "It increases mobility for homeowners. I don't know what tax jurisdiction you are in but you'll tend to get a break on taxes if you are selling your primary residence. For example, if you were to relocate to another location and it was taxed normally, then it will trigger a tax bill on a home, even though you were going to repurpose those funds for a similar home.", "title": "" }, { "docid": "151554", "text": "Given your needs, GNUcash will do swimmingly. I've used it for the past 3 years and while it's a gradual learning process, it's been able to resolve most stuff I've thrown at it. Schedule bills and deposits in the calendar view so I can keep an eye on cash flow. GNUcash has scheduled payments and receipts and reconcilation, should you need them. I prefer to keep enough float to cover monthly expenses in accounts rather than monitor potential shortfalls. Track all my stock and mutual fund investments across numerous accounts. It pulls stock, mutual and bond quotes from lots of places, domestic and foreign. It can also pull transaction data from your brokers, if they support that. I manually enter all my transactions so I can keep control of them. I just reconcile what I entered into Quicken based on the statements sent to me. I do not use Quicken's bill pay There's a reconciliation mode, but I don't use it personally. The purpose of reconcilation is less about catching bank errors and more about agreeing on the truth so that you don't incur bank fees. When I was doing this by hand I found I had a terrible data entry error rate, but on the other hand, the bayesian importer likes to mark gasoline purchases from the local grocery store as groceries rather than gas. I categorize all my expenditures for help come tax time. GNUcash has accounts, and you can mark expense accounts as tax related. It also generates certain tax forms for you if you need that. Not sure what all you're categorizing that's helpful at tax time though. I use numerous reports including. Net Worth tracking, Cash not is retirement funds and total retirement savings. Tons of reports, and the newest version supports SQL backends if you prefer that vs their reports.", "title": "" }, { "docid": "2648", "text": "I am in the process of writing an article about how to maximize one's Social Security benefits, or at least, how to start the analysis. This chart, from my friends at the Social Security office shows the advantage of waiting to take your benefit. In your case, you are getting $1525 at age 62. Now, if you wait 4 years, the benefit jumps to $2033 or $508/mo more. You would get no benefit for 4 years and draw down savings by $73,200, but would get $6,096/yr more from 64 on. Put it off until 70, and you'd have $2684/mo. At some point, your husband should apply for a spousal benefit (age 66 for him is what I suggest) and collect that for 4 years before moving to his own benefit if it's higher than that. Keep in mind, your generous pensions are likely to push you into having your social security benefit taxed, and my plan, above will give you time to draw down the 401(k) to help avoid or at least reduce this.", "title": "" }, { "docid": "72631", "text": "Can you elaborate on how corporate tax cuts exactly drain the economy and destroy jobs? I feel like, going straight off text-book, his tax-plans make sense. It's very possible that I am a really confused student. (Currently second year student) -edit This is my interpretation of the capital-tax-gain-cut proposed by the Trump administration based on what I have learned in Micro/Macro-Econ thus far in college: Less capital tax = less pressure on the wealthy/entrepreneurs (since you keep bigger portion of your net income, the interest to bring back business should increase) = capital inflow back to the US. I feel like I'm missing something big here since a lot of folks seem to be against this, and I want to understand why something is the way it is. Thank you in advance.", "title": "" }, { "docid": "357094", "text": "\"It will count as income, and you can deduct as much of your moving expenses as allowed by tax laws. If you also count it as a reimbursement, then you're double-taxed - once for the income and again by reducing your moving deduction. The \"\"reimbursement\"\" amount is designed for when you get literally reimbursed for exact expenses directly, bypassing the tax on that compensation. The only difference will be that you (and your employer) pay FICA and medicare on the \"\"relocation bonus\"\" that you wouldn't if you were reimbursed. Also, with a reimbursement you are not incentivized to minimize the cost of your relocation (since it's not your money you're spending). With a bonus, since you get to keep whatever is left over, you have a vested interest in keeping your expenses down.\"", "title": "" }, { "docid": "187196", "text": "I have a little experience with this. My home state of Wisconsin was on this list until 2011. The thing to remember is that these states simply do not recognize the HSA. What this means is that there are no state income tax advantages to the account, and no state tax penalties, either. Here are the implications: When you invest in a taxable account, your broker in many cases keeps track of cost basis for you. However, when you invest inside an HSA, your HSA custodian will generally not keep track of any of this, because it is not normally needed. Therefore, you need to keep track of any cost basis yourself, and when you sell, calculate the capital gain or loss on your state return. In my opinion, the HSA is a good deal even if your state does not recognize it. The tax-free savings/investing is a great deal, even if only on your Federal taxes. The state return will be a little more complicated, but the savings you get on your federal return are worth it. In my situation, our family spends the money in the HSA on medical expenses fast enough that we don't invest it in anything other than an interest-bearing savings account. Therefore, we didn't have to worry about capital gains inside our HSA, and only had to add contributions and earnings to our state income. I am very glad that our state now recognizes the HSA.", "title": "" }, { "docid": "240591", "text": "\"It depends on what you're talking about. If this is for your retirement accounts, like IRAs, then ABSOLUTELY NOT! In your retirement accounts you should be broadly diversified - not just between stocks, but also other markets like bonds. Target retirement funds and solid conservative or moderate allocation funds are the best 'quick-and-dirty' recommendation for those accounts. Since it's for the long haul, you want to be managing risk, not chasing returns. Returns will happen over the 40 or so years they have to grow. Now, if you're talking about a taxable stock account, and you've gotten past PF questions like \"\"am I saving enough for retirement\"\", and \"\"have I paid off my debt\"\", then the question becomes a little more murky. First, yes, you should be diversified. The bulk of how a stock's movement will be in keeping with how its sector moves; so even a really great stock can get creamed if its sector is going down. Diversification between several sectors will help balance that. However, you will have some advantage in this sector. Knowing which products are good, which products everybody in the industry is excited about, is a huge advantage over other investors. It'll help you pick the ones that go up more when the sector goes up, and down less when the sector goes down. That, over time and investments, really adds up. Just remember that a good company and a good stock investment are not the same thing. A great company can have a sky-high valuation -- and if you buy it at that price, you can sit there and watch your investment sink even as the company is growing and doing great things. Have patience, know which companies are good and which are bad, and wait for the price to come to you. One final note: it also depends on what spot you are in. If you're a young guy looking looking to invest his first few thousand in the market, then go for it. On the other hand, if you're older, and we're talking about a couple hundred grand you've got saved up, then it's a whole different ball of wax. It that spot, you're back to managing risk, and need to build a solid portfolio, at a measured pace.\"", "title": "" }, { "docid": "12146", "text": "\"I am/was responding to your point that beef prices \"\"should be hitting everyone else harder\"\". Your initial argument was that vertical integration made them better able to beat the competition due to lower beef cost. Clearly not all competition is vertically integrated, so the initial premise warrants exploration. My comments explore my concerns with your premise, despite the fact I am not an expert on beef or Mcdonalds. Your initial premise also misses the point that not all of McD's competition is selling beef. This sort of implies that McDonalds can completely keep costs the same as substitutes just because they are vertically integrated. But I will ignore that for now too. Now you have abandoned your initial premise and are now arguing that derivatives, combined with vertical integration are the cause for the competitive advantage. I am not going to even begin to argue with this because I don't know about McDonalds hedging strategies compared to their competition. I do know that the derivatives are a) available to the competition and b) would be necessary for McDonalds to even begin controlling \"\"beef cost\"\". So, my main point stands, the vertical integration does not significantly help McDonalds control beef costs compared to a pure derivative strategy (regardless of if competition actually uses derivatives).\"", "title": "" }, { "docid": "588172", "text": "looking at flights available, a lot had very full seating. I could save some money if i want a long layover, like 20 hours, but i am not doing that on vacation with kids. I probably could have waited another month or 2 but my wife is a teacher and she was getting nervous about flights filling up. but at $650 per round trip ticket for that spring break week......probably not going to find anything much cheaper. I'll keep an eye on kayak.com, and hope i didn't pull the trigger too soon.", "title": "" }, { "docid": "505134", "text": "\"I am perfectly qualified to not use an accountant. I am a business professor, and my work crosses over into accounting quite a bit. I would certainly find a CPA that is reputable and hire them for advice before starting. I know a physicist who didn't do that and found they ended up with $78,000 in fines. There are a number of specific things an accountant might provide that Quickbooks will not. First and foremost, they are an outsider's set of eyes. If they are good, they will find a polite way to say \"\"you want to do what?!?!?!\"\" If they are good, they won't fall out of their chair, their jaw won't drop to the floor, and they won't giggle until they get home. A good accountant has seen around a hundred successful and unsuccessful businesses. They have seen everything you may have thought of. Intelligence is learning from your own mistakes, wisdom is learning from the mistakes of others. Accountants are the repositories of wisdom. An accountant can point out weaknesses in your plan and help you shore it up. They can provide information about the local market that you may not be aware of. They can assist you with understanding the long run consequences of the legal form that you choose. They can assist you in understanding the trade-offs of different funding models. They can also do tasks that you are not talented at and which will take a lot of time if you do it, and little time if they do it. There is a reason that accountants are required to have 160 semester hours to sit for the CPA. They also have to have a few thousand field hours before they can sit for it as well. There is one thing you may want to keep in mind though. An accountant will often do what you ask them to do, so think about what you want before you visit the accountant. Also, remember to ask the question \"\"is there a question I should have asked but didn't?\"\"\"", "title": "" }, { "docid": "422952", "text": "Five years is too short to be able to safely invest the money in any productive manner. You're saving, not investing. Part of the problem is that you don't have all the money right now, and you'll need to add to it over the next few years until you have enough for a down payment. See the notes under CDs and bonds below for why this is a problem. The universe of options: As for the Roth, as duffbeer703 said, I'm not sure it's worth the hassle and risk that you'll want the money sooner and be forced to wait. (E.g. you end up with enough money in 4.25 years for a house that you want but you have to wait 9 months to be able to tap the Roth.) As noted above, the yields are so low that the losses to taxes aren't really going to amount to much. On $10k you're looking at $150 max earnings, and losing maybe $40 of it to taxes (annually). So avoiding taxes won't shrink your time horizon by any meaningful amount. I'd just open a high yield savings account and start dumping money in. Keep an eye on shorter term (1yr) CD rates and if they go above the savings yield and the timing is right then take advantage of it.", "title": "" }, { "docid": "252843", "text": "FICA taxes are separate from federal and state income taxes. As a sole proprietor you owe all of those. Additionally, there is a difference with FICA when you are employed vs. self employed. Typically FICA taxes are actually split between the employer and the employee, so you pay half, they pay half. But when you're self employed, you pay both halves. This is what is commonly referred to as the self employment tax. If you are both employed and self employed as I am, your employer pays their portion of FICA on the income you earn there, and you pay both halves on the income you earn in your business. Edit: As @JoeTaxpayer added in his comment, you can specify an extra amount to be withheld from your pay when you fill out your W-4 form. This is separate from the calculation of how much to withhold based on dependents and such; see line 6 on the linked form. This could allow you to avoid making quarterly estimated payments for your self-employment income. I think this is much easier when your side income is predictable. Personally, I find it easier to come up with a percentage I must keep aside from my side income (for me this is about 35%), and then I immediately set that aside when I get paid. I make my quarterly estimated payments out of that money set aside. My side income can vary quite a bit though; if I could predict it better I would probably do the extra withholding. Yes, you need to pay taxes for FICA and federal income tax. I can't say exactly how much you should withhold though. If you have predictable deductions and such, it could be lower than you expect. I'm not a tax professional, and when it comes doing business taxes I go to someone who is. You don't have to do that, but I'm not comfortable offering any detailed advice on how you should proceed there. I mentioned what I do personally as an illustration of how I handle withholding, but I can't say that that's what someone else should do.", "title": "" }, { "docid": "359579", "text": "I am not going to argue the merits of investing in real estate (I am a fan I think it is a great idea when done right). I will assume you have done your due diligence and your numbers are correct, so let's go through your questions point by point. What would be the type of taxes I should expect? NONE. You are a real estate investor and the US government loves you. Everything is tax deductible and odds are your investment properties will actually manage to shelter some of your W2(day job) income and you will pay less taxes on that too. Obviously I am exaggerating slightly find a CPA (certified public accountant) that is familiar with real estate, but here are a few examples. I am not a tax professional but hopefully this gives you an idea of what sort of tax benifits you can expect. How is Insurance cost calculated? Best advice I have call a few insurance firms and ask them. You will need landlord insurance make sure you are covered if a tenant gets hurt or burns down your property. You can expect to pay 15%-20% more for landlord insurance than regular insurance (100$/month is not a bad number to just plug in when running numbers its probably high). Also your lease should require tenants to have renters insurance to help protect you. Have a liability conversation with a lawyer and think about LLCs. How is the house price increase going to act as another source of income? Appreciation can be another source of income but it is not really that useful in your scenario. It is not liquid you will not realize it until you sell the property and then you have to pay capital gains and depreciation recapture on it. There are methods to get access to the gains on the property without paying taxes. This is done by leveraging the property, you get the equity but it is not counted as capital gains since you have to pay it back a mortgage or home equity lines of credit (HELOC) are examples of this. I am not recommending these just making sure you are aware of your options. Please let me know if I am calculating anything wrong but my projection for one year is about $8.4k per house (assuming no maintenance is needed) I would say you estimated profit is on the high side. Not being involved in your market it will be a wild guess but I would expect you to realize cash-flow per house per year of closer to $7,000. Maybe even lower given your inexperience. Some Costs you need to remember to account for: Taxes, Insurance, Vacancy, Repairs, CapEx, Property Management, Utilities, Lawn Care, Snow Removal, HOA Fees. All-in-all expect 50% or your rental income to be spent on the property. If you do well you can be pleasantly surprised.", "title": "" } ]
883	Omnivores produce more trimethylamine N-oxide from dietary I-carnitine than vegans.	[ { "docid": "14803797", "text": "Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.", "title": "Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis" } ]	[ { "docid": "6327940", "text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.", "title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity." }, { "docid": "33684572", "text": "Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.", "title": "Transmission of atherosclerosis susceptibility with gut microbial transplantation." }, { "docid": "12709184", "text": "IMPORTANCE Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and mortality. DESIGN Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. SETTING Adventist Health Study 2 (AHS-2), a large North American cohort. PARTICIPANTS A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73,308 participants remained after exclusions. EXPOSURES Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. MAIN OUTCOME AND MEASURE The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. RESULTS There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82-6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. CONCLUSIONS AND RELEVANCE Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.", "title": "Vegetarian dietary patterns and mortality in Adventist Health Study 2." }, { "docid": "39187170", "text": "Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.", "title": "Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity." }, { "docid": "6793674", "text": "Circulating trimethylamine N-oxide (TMAO), a canonical metabolite from gut flora, has been related to the risk of cardiovascular disorders. However, the association between circulating TMAO and the risk of cardiovascular events has not been quantitatively evaluated. We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating TMAO and subsequent cardiovascular events. Embase and PubMed databases were searched for relevant cohort studies. The overall hazard ratios for the developing of cardiovascular events (CVEs) and mortality were extracted. Heterogeneity among the included studies was evaluated with Cochran's Q Test and I2 statistics. A random-effect model or a fixed-effect model was applied depending on the heterogeneity. Subgroup analysis and meta-regression were used to evaluate the source of heterogeneity. Among the 11 eligible studies, three reported both CVE and mortality outcome, one reported only CVEs and the other seven provided mortality data only. Higher circulating TMAO was associated with a 23% higher risk of CVEs (HR = 1.23, 95% CI: 1.07-1.42, I2 = 31.4%) and a 55% higher risk of all-cause mortality (HR = 1.55, 95% CI: 1.19-2.02, I2 = 80.8%). Notably, the latter association may be blunted by potential publication bias, although sensitivity analysis by omitting one study at a time did not significantly change the results. Further subgroup analysis and meta-regression did not support that the location of the study, follow-up duration, publication year, population characteristics or the samples of TMAO affect the results significantly. Higher circulating TMAO may independently predict the risk of subsequent cardiovascular events and mortality.", "title": "Circulating trimethylamine N‐oxide and the risk of cardiovascular diseases: a systematic review and meta‐analysis of 11 prospective cohort studies" }, { "docid": "11181416", "text": "Because arginase hydrolyzes arginine to produce ornithine and urea, it has the potential to regulate nitric oxide (NO) and polyamine synthesis. We tested whether expression of the cytosolic isoform of arginase (arginase I) was limiting for NO or polyamine production by activated RAW 264.7 macrophage cells. RAW 264.7 cells, stably transfected to overexpress arginase I or beta-galactosidase, were treated with interferon-gamma to induce type 2 NO synthase or with lipopolysaccharide or 8-bromo-cAMP (8-BrcAMP) to induce ornithine decarboxylase. Overexpression of arginase I had no effect on NO synthesis. In contrast, cells overexpressing arginase I produced twice as much putrescine after activation than did cells expressing beta-galactosidase. Cells overexpressing arginase I also produced more spermidine after treatment with 8-BrcAMP than did cells expressing beta-galactosidase. Thus endogenous levels of arginase I are limiting for polyamine synthesis, but not for NO synthesis, by activated macrophage cells. This study also demonstrates that it is possible to alter arginase I levels sufficiently to affect polyamine synthesis without affecting induced NO synthesis.", "title": "Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?" }, { "docid": "35962023", "text": "Recent studies suggest a close relationship between cell metabolism and apoptosis. We have evaluated changes in lipid metabolism on permeabilized hepatocytes treated with truncated Bid (tBid) in the presence of caspase inhibitors and exogenous cytochrome c. The measurement of β-oxidation flux by labeled palmitate demonstrates that tBid inhibits β-oxidation, thereby resulting in the accumulation of palmitoyl-coenzyme A (CoA) and depletion of acetyl-carnitine and acylcarnitines, which is pathognomonic for inhibition of carnitine palmitoyltransferase-1 (CPT-1). We also show that tBid decreases CPT-1 activity by a mechanism independent of both malonyl-CoA, the key inhibitory molecule of CPT-1, and Bak and/or Bax, but dependent on cardiolipin decrease. Overexpression of Bcl-2, which is able to interact with CPT-1, counteracts the effects exerted by tBid on β-oxidation. The unexpected role of tBid in the regulation of lipid β-oxidation suggests a model in which tBid-induced metabolic decline leads to the accumulation of toxic lipid metabolites such as palmitoyl-CoA, which might become participants in the apoptotic pathway.", "title": "tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl-CoA-independent inhibition of carnitine palmitoyltransferase-1" }, { "docid": "44693226", "text": "Many studies have shown that caloric restriction (40%) decreases mitochondrial reactive oxygen species (ROS) generation in rodents. Moreover, we have recently found that 7 weeks of 40% protein restriction without strong caloric restriction also decreases ROS production in rat liver. This is interesting since it has been reported that protein restriction can also extend longevity in rodents. In the present study we have investigated the possible role of dietary lipids in the effects of caloric restriction on mitochondrial oxidative stress. Using semipurified diets, the ingestion of lipids in male Wistar rats was decreased by 40% below controls, while the other dietary components were ingested at exactly the same level as in animals fed ad libitum. After 7 weeks of treatment the liver mitochondria of lipid-restricted animals showed significant increases in oxygen consumption with complex I-linked substrates (pyruvate/malate and glutamate/malate). Neither mitochondrial H(2)O(2) production nor oxidative damage to mitochondrial or nuclear DNA was modified in lipid-restricted animals. Oxidative damage to mitochondrial DNA was one order of magnitude higher than that of nuclear DNA in both dietary groups. These results deny a role for lipids and reinforce the possible role of dietary proteins as being responsible for the decrease in mitochondrial ROS production and DNA damage in caloric restriction.", "title": "Effect of lipid restriction on mitochondrial free radical production and oxidative DNA damage." }, { "docid": "22995164", "text": "Nitrosoglutathione [(GSNO), 500 nmol/l] relaxed the norepinephrine precontracted rat aortic rings. The relaxation effect was pronouncedly enhanced by H2S- and HS−-donor NaHS (30 μmol/l) at 7.5 pH but not at 6.3 pH. To study molecular mechanism of this effect, we investigated whether NaHS can release NO from NO donors. Using an electron paramagnetic resonance spectroscopy method of spin trap and by measuring the NO oxidation product, which is nitrite, by the Griess reaction, we report that NaHS released NO from nitrosothiols, namely from GSNO, S-nitroso-N-acetyl-dl-penicillamine (SNAP), from metal nitrosyl complex nitroprusside (SNP) and from rat brain homogenate and murine L1210 leukaemia cells. From the observation that the releasing effect was more pronounced at 8.0 pH than 6.0 pH, we suppose that HS−, rather than H2S, is responsible for the NO-releasing effect. Since in mammals, H2S and HS− are produced endogenously, we assume that their effect to release NO from nitrosothiols and from metal nitrosyl complexes are responsible for some of their biological activities and that this mechanism may be involved in S-nitrosothiol-signalling reactions.", "title": "H2S and HS− donor NaHS releases nitric oxide from nitrosothiols, metal nitrosyl complex, brain homogenate and murine L1210 leukaemia cells" }, { "docid": "13380011", "text": "Partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinson's disease in rodents. The hypothesis that rotenone enhancement of neuronal cell death is attributable to oxidative stress was tested in an acute glutamate excitotoxicity model using primary cultures of rat cerebellar granule neurons. As little as 5 nM rotenone increased mitochondrial superoxide (O2-) levels and potentiated glutamate-induced cytoplasmic Ca2+ deregulation, the first irreversible stage of necrotic cell death. However, the potent cell-permeant O2- trap manganese tetrakis (N-ethylpyridinium-2yl) porphyrin failed to prevent the effects of the inhibitor. The bioenergetic consequences of rotenone addition were quantified by monitoring cell respiration. Glutamate activation of NMDA receptors used the full respiratory capacity of the in situ mitochondria, and >80% of the glutamate-stimulated respiration was attributable to increased cellular ATP demand. Rotenone at 20 nM inhibited basal and carbonyl cyanide p-trifluoromethoxyphenylhydrazone-stimulated cell respiration and caused respiratory failure in the presence of glutamate. ATP synthase inhibition by oligomycin was also toxic in the presence of glutamate. We conclude that the cell vulnerability in the rotenone model of partial complex I deficiency under these specific conditions is primarily determined by spare respiratory capacity rather than oxidative stress.", "title": "Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone." }, { "docid": "24349992", "text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.", "title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells." }, { "docid": "15615957", "text": "UNLABELLED Fruit and vegetable consumption has been inversely associated with the risk of chronic diseases including cancer and cardiovascular disease, with the beneficial effects attributed to a variety of protective antioxidants, carotenoids and phytonutrients. The objective of the present study was to determine the effect of supplementation with dehydrated concentrates from mixed fruit and vegetable juices (Juice Plus+R) on serum antioxidant and folate status, plasma homocysteine levels and markers for oxidative stress and DNA damage. Japanese subjects (n=60; age 27.8 yrs; BMI 22.1) were recruited to participate in a double-blind placebo controlled study and were randomized into 2 groups of 30, matched for sex, age, BMI and smoking status (39 males, 22 smokers; 21 females, 13 smokers). Subjects were given encapsulated supplements containing mixed fruit and vegetable juice concentrates or a matching placebo for 28 days, with blood and urine samples collected at baseline, day 14 and day 28 for analytical testing. Compared with the placebo, 28 day supplementation significantly increased the concentration of serum beta-carotene 528% (p<0.0001), lycopene 80.2% (p<0.0005), and alpha tocopherol 39.5% (p<0.0001). Serum folate increased 174.3% (p<0.0001) and correlated with a decrease in plasma homocysteine of -19.9% (p<0.03). Compared with baseline, measures of oxidative stress decreased with serum lipid peroxides declining -10.5% (p<0.02) and urine 8OHdG decreasing -21.1% (p<0.02). Evaluation of data from smokers only (n=17) after 28 days of active supplementation showed comparable changes. CONCLUSION In the absence of dietary modification, supplementation with the fruit and vegetable juice concentrate capsules proved to be a highly bioavailable source of phytonutrients. Important antioxidants were elevated to desirable levels associated with decreased risk of disease while markers of oxidative stress were reduced, and folate status improved with a concomitant decrease in homocysteine, and these benefits occurred to a similar extent in smokers when compared to non-smokers.", "title": "Original Article" }, { "docid": "35828148", "text": "Apocynin has been reported to require dimerization by myeloperoxidase (MPO) to inhibit leukocyte NADPH oxidase. (-)-Epicatechin, a dietary flavan-3-ol, has been identified as a 'prodrug' of apocynin-like metabolites that inhibit endothelial NADPH oxidase activity and elevate the cellular level of nitric oxide. Since (-)-epicatechin has tentatively been identified as substrate of MPO, we studied the one-electron oxidation of (-)-epicatechin by MPO. By using multi-mixing stopped-flow technique, we demonstrate that (-)-epicatechin is one of the most efficient electron donors for heme peroxidases investigated so far. Second order rate constants for the (-)-epicatechin-mediated conversion of MPO-compound I to compound II and compound II to resting enzyme were estimated to be 1.9 x 10(7) and 4.5 x 10(6) M(-1)s(-1), respectively (pH 7, 25 degrees C). The data indicate that (-)-epicatechin is capable of undergoing fast MPO-mediated one-electron oxidation.", "title": "Kinetic evidence for rapid oxidation of (-)-epicatechin by human myeloperoxidase." }, { "docid": "25974070", "text": "The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.", "title": "Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function." }, { "docid": "5687200", "text": "AIMS The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. METHODS A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. RESULTS Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. CONCLUSIONS A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.", "title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes" }, { "docid": "6191684", "text": "CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects. OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches. DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53). MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group. RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.", "title": "Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial." }, { "docid": "28644298", "text": "Epstein-Barr virus (EBV) latency III infection converts B lymphocytes into lymphoblastoid cell lines (LCLs) by expressing EBV nuclear and membrane proteins, EBNAs, and latent membrane proteins (LMPs), which regulate transcription through Notch and tumor necrosis factor receptor pathways. The role of NF-kappa B in LMP1 and overall EBV latency III transcriptional effects was investigated by treating LCLs with BAY11-7082 (BAY11). BAY11 rapidly and irreversibly inhibited NF-kappa B, decreased mitochondrial membrane potential, induced apoptosis, and altered LCL gene expression. BAY11 effects were similar to those of an NF-kappa B inhibitor, Delta N-I kappa B alpha, in effecting decreased JNK1 expression and in microarray analyses. More than 80% of array elements that decreased with Delta N-I kappa B alpha expression decreased with BAY11 treatment. Newly identified NF-kappa B-induced, LMP1-induced, and EBV-induced genes included pleckstrin, Jun-B, c-FLIP, CIP4, and I kappa B epsilon. Of 776 significantly changed array elements, 134 were fourfold upregulated in EBV latency III, and 74 were fourfold upregulated with LMP1 expression alone, whereas only 28 were more than fourfold downregulated by EBV latency III. EBV latency III-regulated gene products mediate cell migration (EBI2, CCR7, RGS1, RANTES, MIP1 alpha, MIP1 beta, CXCR5, and RGS13), antigen presentation (major histocompatibility complex proteins and JAW1), mitogen-activated protein kinase pathway (DUSP5 and p62Dok), and interferon (IFN) signaling (IFN-gamma R alpha, IRF-4, and STAT1). Comparison of EBV latency III LCL gene expression to immunoglobulin M (IgM)-stimulated B cells, germinal-center B cells, and germinal-center-derived lymphomas clustered LCLs with IgM-stimulated B cells separately from germinal-center cells or germinal-center lymphoma cells. Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signaling pathways further distinguished EBV latency III-infected B cells from IgM-stimulated or germinal-center B cells.", "title": "Role of NF-kappa B in cell survival and transcription of latent membrane protein 1-expressing or Epstein-Barr virus latency III-infected cells." }, { "docid": "24594624", "text": "Maternal diabetes mellitus is a significant risk factor for structural birth defects, including congenital heart defects and neural tube defects. With the rising prevalence of type 2 diabetes mellitus and obesity in women of childbearing age, diabetes mellitus-induced birth defects have become an increasingly significant public health problem. Maternal diabetes mellitus in vivo and high glucose in vitro induce yolk sac injuries by damaging the morphologic condition of cells and altering the dynamics of organelles. The yolk sac vascular system is the first system to develop during embryogenesis; therefore, it is the most sensitive to hyperglycemia. The consequences of yolk sac injuries include impairment of nutrient transportation because of vasculopathy. Although the functional relationship between yolk sac vasculopathy and structural birth defects has not yet been established, a recent study reveals that the quality of yolk sac vasculature is related inversely to embryonic malformation rates. Studies in animal models have uncovered key molecular intermediates of diabetic yolk sac vasculopathy, which include hypoxia-inducible factor-1α, apoptosis signal-regulating kinase 1, and its inhibitor thioredoxin-1, c-Jun-N-terminal kinases, nitric oxide, and nitric oxide synthase. Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid and myo-inositol. Dietary supplementation with fatty acids that restore lipid levels in the yolk sac lead to a reduction in diabetes mellitus-induced malformations. Although the role of the human yolk in embryogenesis is less extensive than in rodents, nevertheless, human embryonic vasculogenesis is affected negatively by maternal diabetes mellitus. Mechanistic studies have identified potential therapeutic targets for future intervention against yolk sac vasculopathy, birth defects, and other complications associated with diabetic pregnancies.", "title": "New development of the yolk sac theory in diabetic embryopathy: molecular mechanism and link to structural birth defects." }, { "docid": "19327364", "text": "Sera from 526 Old-World monkeys and apes, representing 50 species and 20 genera and living in US zoos and vivaria, were screened for antibodies to HTLV-I, HTLV-III/LAV, and simian-AIDS retrovirus, type I (SRV-I). Sera were screened initially by ELISA, and ELISA-positive sera, as well as ELISA-negative sera from cage contacts, were further tested by Western blotting. A large number of false-positive and a small number of false-negative ELISA sera were identified. Although most true positive reactions were directed to a single retrovirus, a number of individuals from 4 species were positive for more than one retrovirus. Specific seroreactivity to HTLV-I was found in 39/526 (7%) animals of 15 species. True positive reactions to SRV-I were found in 21/516 (4%) animals, including talapoins and 2 species of macaques. Specific serologic reactions to HTLV-III/LAV were detected in 23/526 (4%) monkeys. Many of the HTLV-III/LAV seropositive animals were from one mixed-species zoo exhibit, containing sooty mangabeys, mandrills, Kolb's guenons, and talapoins. A type D virus was isolated from the blood of 3/10 SRV-I antibody-positive Tonkeana macaques, but from none of 11 seropositive talapoins. A lentivirus was isolated from the blood of 4/7 HTLV-III/LAV seropositive sooty mangabeys, but not from seropositive talapoins in the same exhibit or from 2 seropositive colobus from another zoo. The sooty mangabey lentivirus produced generalized lymphadenopathy, leukopenia, and decreased levels of T4 lymphocytes in 2 experimentally infected rhesus macaques.", "title": "Seroepidemiologic survey of captive Old-World primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys)." }, { "docid": "23245050", "text": "Dietary status was evaluated in eight highly trained female cyclists. Each cyclist kept a 3-day weighed food record. Diets were analyzed for nutrient content using a computerized software package. Blood was also obtained and evaluated for hemoglobin, hematocrit, and albumin. For an athletic group, the cyclists' diets were found to be low in energy (85% RDA) and carbohydrate (4.4 gm/kg body weight per day). Mean daily dietary intakes were well below the RDAs for folacin (76% RDA), magnesium (81%), iron (59%), and zinc (48%). In addition, more than one-third of the cyclists failed to consume 67% of the RDA for the following micronutrients: pyridoxine, folacin, cobalamin, vitamin E, magnesium, iron, and zinc. Hemoglobin (135 gm/L), hematocrit (0.39), and albumin (45 gm/L) values were all normal, although most hemoglobin values were in the lower 50% of normal range. Foods such as meats, poultry, fish, beans, peas, and nuts were low or absent from the diets of most athletes. Dietary quality in this group of female cyclists could have been greatly improved with the addition of more of those foods. These athletes could benefit from nutrition education and diet counseling.", "title": "Dietary status of trained female cyclists." }, { "docid": "25135304", "text": "The purpose of this study was to examine the relation of leptin to metabolic and dietary factors in college-age adults. Young adult women and men (n = 32) were recruited and underwent testing for measurement of body mass index, body composition, peak oxygen consumption (VO2peak), dietary intake, and plasma levels of leptin and insulin. Ln leptin was significantly greater for women than for men (2.1 versus 1.2 ng/mL, respectively). This difference remained significant even after adjusting ln leptin for fat mass and fat-free mass as covariates in separate analyses. VO2peak was higher for men than for women and this remained significant after adjustment for differences in fat-free mass and total body mass. Significant correlations were found between ln leptin and indicators of fat mass in women and men, with higher correlations for similar variables observed in men (r = 0.548, 0.674, and 0.732 for body mass index, percentage of body fat, and fat mass [kg] for women, respectively, and r = 0.740, 0.888, 0.858 for body mass index, percentage of body fat, and fat mass [kg] for men, respectively). Ln leptin showed a significant inverse relationship with VO2peak (r = -0.751) in men only. After adjusting ln leptin for body fat mass using partial correlations, ln leptin was not significantly associated with any of the measured variables. Alternatively, after normalization of ln leptin using fat mass as the divisor, a less adequate statistical analysis method, men showed statistical significant correlations between ln leptin and dietary intake and VO2peak. Although plasma leptin values were higher in women, stronger associations were evident for men than for women between leptin and metabolic and dietary factors.", "title": "Relation of plasma leptin concentrations to sex, body fat, dietary intake, and peak oxygen uptake in young adult women and men." }, { "docid": "20672596", "text": "Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.", "title": "Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages." }, { "docid": "2659805", "text": "A number of methods have been developed to assist subjects in providing an estimate of portion size but their application in improving portion size estimation by children has not been investigated systematically. The aim was to develop portion size assessment tools for use with children and to assess the accuracy of children's estimates of portion size using the tools. The tools were food photographs, food models and an interactive portion size assessment system (IPSAS). Children (n 201), aged 4-16 years, were supplied with known quantities of food to eat, in school. Food leftovers were weighed. Children estimated the amount of each food using each tool, 24 h after consuming the food. The age-specific portion sizes represented were based on portion sizes consumed by children in a national survey. Significant differences were found between the accuracy of estimates using the three tools. Children of all ages performed well using the IPSAS and food photographs. The accuracy and precision of estimates made using the food models were poor. For all tools, estimates of the amount of food served were more accurate than estimates of the amount consumed. Issues relating to reporting of foods left over which impact on estimates of the amounts of foods actually consumed require further study. The IPSAS has shown potential for assessment of dietary intake with children. Before practical application in assessment of dietary intake of children the tool would need to be expanded to cover a wider range of foods and to be validated in a 'real-life' situation.", "title": "Children's estimates of food portion size: the development and evaluation of three portion size assessment tools for use with children." }, { "docid": "22889972", "text": "Inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) have been implicated in atherogenesis. However, the precise role of TNF-alpha in atherogenesis is still unclear. To examine the effect of TNF-alpha on atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) and TNF-alpha (apoE-/-/TNF-alpha-/-) and compared them with apoE-/- mice. Although serum total cholesterol levels were markedly elevated in both apoE-/-/TNF-alpha-/- and apoE-/- mice compared to wild-type mice, no differences were observed between apoE-/-/TNF-alpha-/- and apoE-/- mice. The atherosclerotic plaque area in the aortic luminal surface of apoE-/-/TNF-alpha-/- mice (n=8, 3.1+/-0.4%) was significantly smaller than that of apoE-/- mice (n=7, 4.7+/-0.4%, p<0.001) despite the lack of difference in serum cholesterol levels. The atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-alpha-/- mice (n=10, 5.1+/-0.3 x 10(5)microm(2)) was also significantly smaller than that of apoE-/- mice (n=11, 7.0+/-0.3 x 10(5)microm(2), p<0.0001). RT-PCR analysis indicated that the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF-alpha-/- mice. Macrophages from apoE(-/-) mice showed higher uptake level of oxidized LDL and increased expression level of scavenger receptor class A (SRA) compared to those from apoE-/-/TNF-alpha-/- mice. These results indicate that TNF-alpha plays an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in macrophages.", "title": "Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice." }, { "docid": "43048059", "text": "AIMS The present study aims to investigate the interaction between nitric oxide (NO) and hydrogen sulfide (H(2)S), the two important gaseous mediators in rat hearts. METHODS AND RESULTS Intracellular calcium in isolated cardiomyocytes was measured with a spectrofluorometric method using Fura-2. Myocyte contractility was measured with a video edge system. NaHS (50 µM, an H(2)S donor) had no significant effect on the resting calcium level, electrically induced (EI) calcium transients, and cell contractility in ventricular myocytes. Stimulating endogenous NO production with l-arginine or exogenous application of NO donors [sodium nitroprusside (SNP) and 2-(N,N-diethylamino)-diazenolate-2-oxide] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lusitropic effects of the above three NO-increasing agents. In addition, the mixture of SNP + NaHS increased, whereas SNP alone decreased, the resting calcium level and the amplitudes of EI calcium transients. Angeli's salt, a nitroxyl anion (HNO) donor, mimicked the effect of SNP + NaHS on calcium handling and myocyte contractility. Three thiols, N-acetyl-cysteine, l-cysteine, and glutathione, abolished the effects of HNO and SNP + NaHS on myocyte contraction. Neither Rp-cAMP [a protein kinase A (PKA) inhibitor] nor Rp-cGMP [a protein kinase G (PKG) inhibitor] affected the effects of SNP + NaHS, suggesting a cAMP/PKA- or cGMP/PKG-independent mechanism. CONCLUSION H(2)S may interact with NO to form a thiol sensitive molecule (probably HNO) which produces positive inotropic and lusitropic effects. Our findings may shed light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.", "title": "Hydrogen sulfide interacts with nitric oxide in the heart: possible involvement of nitroxyl." }, { "docid": "41310252", "text": "The epidemiological evidence that a high-fat diet promotes the development of obesity is considered suggestive but not definitive. The purpose of this paper is to provide a review of various epidemiological methods that have been used to address this issue as well as an updated summary of the existing evidence. Ecological studies describing dietary fat intake and obesity at the population level provide mixed results and are likely to be biased by both confounding and unknown data quality factors that differ systematically across the populations studied. Cross-sectional studies are generally in agreement that the concentration of fat in the diet is positively associated with relative weight. Prospective studies of diet in relation to subsequent weight change give inconsistent results. This may be due to behavioural factors such as dieting in response to weight gain; in addition, this type of study rarely takes into account the possible interaction between genetic predisposition and dietary fat in promoting weight gain. Finally, intervention studies in free-living subjects are considered, providing evidence of a consistent but short-lived period of active weight loss on low-fat diets. The experimental evidence on this relationship is more conclusive than the epidemiological evidence, although biological mechanisms remain controversial. Some areas for future epidemiological research involve: longitudinal studies of dietary fat intake as a predictor of growth in children; observational studies relating total dietary fat and specific types of fat to overall as well as regional adiposity; and randomized intervention studies of the effect of low-fat diets with particular emphasis on and familial predisposition to obesity and other possible modifying factors.", "title": "Dietary fat and obesity: evidence from epidemiology." }, { "docid": "2139357", "text": "BACKGROUND The role of the diffusible messenger nitric oxide (NO) in the regulation of pain transmission is still a debate of matter, pro-nociceptive and/or anti-nociceptive. S-Nitrosylation, the reversible post-translational modification of selective cysteine residues in proteins, has emerged as an important mechanism by which NO acts as a signaling molecule. The occurrence of S-nitrosylation in the spinal cord and its targets that may modulate pain transmission remain unclarified. The \"biotin-switch\" method and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were employed for identifying S-nitrosylated proteins. RESULTS Here we show that actin was a major protein S-nitrosylated in the spinal cord by the NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP). Interestingly, actin was S-nitrosylated, more in the S2 fraction than in the P2 fraction of the spinal homogenate. Treatment of PC12 cells with SNAP caused rapid S-nitrosylation of actin and inhibited dopamine release from the cells. Just like cytochalasin B, which depolymerizes actin, SNAP decreased the amount of filamentous actin cytoskeleton just beneath the membrane. The inhibition of dopamine release was not attenuated by inhibitors of soluble guanylyl cyclase and cGMP-dependent protein kinase. CONCLUSION The present study demonstrates that actin is a major S-nitrosylated protein in the spinal cord and suggests that NO directly regulates neurotransmitter release by S-nitrosylation in addition to the well-known phosphorylation by cGMP-dependent protein kinase.", "title": "Involvement of S-nitrosylation of actin in inhibition of neurotransmitter release by nitric oxide" }, { "docid": "13714201", "text": "Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness. Methods and results We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 × 10-4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing-two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3-12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing.", "title": "Gut microbial diversity is associated with lower arterial stiffness in women" }, { "docid": "16252863", "text": "The list of preventable and reversible risk factors for atherosclerotic cardiovascular disease continues to grow. Cigarette smoking, high blood pressure, physical inactivity, elevated cholesterol, underlying lipoprotein abnormalities, lipoprotein(a), diabetes, overweight, male gender, and age are well-established risk factors. During the 1990s, there have been many reports associating elevated plasma homocysteine levels with arteriosclerotic cardiovascular disease and consistent evidence that dietary and supplemental folic acid can reduce homocysteine levels.1 2 The article by Robinson and colleagues3 in this issue of Circulation presents further evidence of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors. Their study is part of the European Concerted Action Project,4 which examined 750 patients younger than age 60 with diagnoses within the previous 12 months of coronary, cerebrovascular, or peripheral vascular disease and 800 healthy control subjects. The patient groups were young (47 years for cases and 44 years for control subjects) and heterogeneous, with nonfatal clinical events or symptoms of arteriosclerotic cardiovascular disease supported by ECG, angiographic, or Doppler evidence; the study involved 19 centers in nine European countries. Men in the highest quintile for fasting total homocysteine (tHcy), compared with the remainder of the population, had an estimated relative risk of 2.2 (95% confidence interval [CI], 1.6 to 2.9), with a striking dose-response relationship and a more-than-multiplicative interaction with cigarette smoking and high blood pressure on vascular disease risk4 ; the corresponding estimated relative risk for coronary heart disease was similar (2.0; 95% CI 1.6 to 2.8). (tHcy is the sum of homocysteine and homocysteinyl moieties of oxidized disulfides, homocystine, and cysteine- homocysteine. ) Robinson and colleagues3 examined three B vitamins in detail to determine their effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease …", "title": "Preventing coronary heart disease: B vitamins and homocysteine." }, { "docid": "37336085", "text": "PURPOSE We assessed the nephroprotective effects of montelukast sodium and N-acetylcysteine on secondary renal damage due to unilateral ureteral obstruction in a rat model. MATERIALS AND METHODS In this study 30 Wistar albino male rats were randomized into 3 groups, including placebo, N-acetylcysteine and montelukast sodium. Three rats served as the control group. The left ureter of the rats was sutured with 4-zero polyglactin sutures. Medications were given 3 days before obstruction and continued for 15 days. Dimercaptosuccinic acid renal scintigraphy was performed before obstruction and on day 15. Rats were sacrificed on day 15 and histopathological examinations were done. We biochemically assessed oxidative stress markers (myeloperoxidase and malondialdehyde), sulfhydryl and total nitrite for lipid peroxidation, oxidative protein damage and antioxidant levels, respectively. RESULTS On pathological examination inflammation and tubular epithelial damage in the N-acetylcysteine and montelukast sodium groups were less than in the placebo group (p <0.05). No difference was seen in normal kidneys. Myeloperoxidase, malondialdehyde and total nitrite levels in the N-acetylcysteine group, and myeloperoxidase and malondialdehyde levels in the montelukast sodium group were lower than in the placebo group (p <0.05). No statistical difference was seen in sulfhydryl levels (p >0.05) or among the N-acetylcysteine, montelukast sodium and placebo groups on scintigraphy (p >0.05). No pathological, chemical and scintigraphic differences were seen among the N-acetylcysteine, montelukast sodium and sham treated groups (p >0.05). CONCLUSIONS N-acetylcysteine and montelukast sodium have a protective effect against obstructive damage of the kidney. However, further investigations are needed.", "title": "Do Montelukast Sodium and N-Acetylcysteine Have a Nephroprotective Effect on Unilateral Ureteral Obstruction? A Placebo Controlled Trial in a Rat Model." } ]
7760	What is the best strategy for after hours trading?	[ { "docid": "16806", "text": "I would never trade after hours and I have 30 years of trading experience. It is a very volatile emotion driven market without a lot of the big players that arbitrage wrong pricing. If I were you I would simply use limit orders you input while the market is closed. If you want to get kute you can put in low-ball offers (and vice versa) to see if they get filled in the volatility at market open. Then check in (when?) when you wake up (or before you go to bed, etc) and revise the limit if not filled. In other words don't 'trade'. Know what your company is worth and put in orders that reflect that.", "title": "" }, { "docid": "240744", "text": "First you will need a plan stating three main points: You will have to decide what criteria you will use to answer these points. You might use Fundamental Analysis to find what to buy and Technical Analysis to decide when to buy and when to sell (your buy and sell triggers). Once you have a Trading Plan in place you would need to find a broker with conditional orders. You can place conditional buy orders to get in a trade (for example if the price moves above or below a target price). You can place conditional stop loss orders if your trade goes against you, and you can also place conditional profit target stops to automatically get out if rises to your desired profit target. You can place one, two or many conditional orders after hours which will enable you to trade without being in front of your screen all day long.", "title": "" } ]	[ { "docid": "396657", "text": "The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. A simple strategy for this is shown in the chart below: I would be buying this stock when the price hits or gets very close to the trendline and then it bounces back above it. I would then have sold this stock once it has broken through below the trendline. This may also be an appropriate time if you were looking to short this stock. Other indicators could also be used in combination for additional confirmation of what is happening to the price. Another type of trader is called a bottom fisher. A bottom fisher would wait until a break above the downtrend line (second chart) and buy after confirmation of a higher high and possibly a higher low (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles, whether you prefer short term trading or longer term investing, and your appetite for risk. You can develop strategies using various indicators and then paper trade or backtest these strategies. You can also manually backtest a strategy in most charting packages. You can go back in time on the chart so that the right side of the chart shows a date in the past (say one year ago or 10 years ago), then you can click forward one day at a time (or one week at a time if using weekly charts). With your indicators on the chart you can do virtual trades to buy or sell whenever a signal is given as you move forward in time. This way you may be able to check years of data in a day to see if your strategy works. Whatever you do, you need to document your strategies in writing in a written trading or investment plan together with a risk management strategy. You should always follow the rules in your written plan to avoid you making decisions based on emotions. By backtesting or paper trading your strategies it will give you confidence that they will work over the long term. There is a lot of work involved at the start, but once you have developed a documented strategy that has been thoroughly backtested, it will take you minimal time to successfully manage your investments. In my shorter term trading (positions held from a couple of days to a few weeks) I spend about half an hour per night to manage my trades and am up about 50% over the last 7 months. For my longer term investing (positions held from months to years) I spend about an hour per week and have been averaging over 25% over the last 4 years. Technical Analysis does work for those who have a documented plan, have approached it in a systematic way and use risk management to protect their existing and future capital. Most people who say that is doesn't work either have not used it themselves or have used it ad-hock without putting in the initial time and work to develop a documented and systematic approach to their trading or investing.", "title": "" }, { "docid": "220110", "text": "Very common question. There is no any rule of thumb. This solely depends on your trading strategy. I will share my own experience. My day starts with the daily chart, if I have a signal, either I open my position or I check 30 minute chart to make sure that it won't go too much against my trade. and I open my position. If I am waiting for the signal the minimum timeframe is 4 hours for me. I use 30 minutes to find the best time to enter the market. So, this is totally something special for my trading strategy, that is why those things can change based on the different strategies. I also check weekly and monthly charts to confirm trend. I have been busy with forex since 2007 and I am a verified investor on etoro At the end, I never use 1,5,15,60 minute charts as they are against my strategy.", "title": "" }, { "docid": "118712", "text": "In general a stock can open at absolutely any price with no regard for the closing price or after hours price the previous day. The opening price will be determined by the best bid and offer made by people who decide to trade the next day. Some of the those people may have put orders in on a prior day that are still on the books and matter, but there's a lot of time overnight for people to cancel orders and enter new ones, which is especially likely to happen if there was substantive news overnight. As for what you can do in your case, you have the same options that you always had: Sell or hold. If you're selling, you can sell after hours, in the pre-open hours, or during the trading day. There's nothing we can say about this case that's really any different than we can say about any other stock on any other day.", "title": "" }, { "docid": "361163", "text": "The sentiment is because between closing and opening a lot can happen, and between opening and the time your order actually goes through, even more can happen. An after-hours trade has an extra amount of short-term risk attached; the price of a stock at the opening bell is technically the same as its price as of the closing the previous trading day, but within a tenth of a second, which is forever in a computerized exchange, that price may move drastically one way or the other, based on news and on other markets. The sentiment, therefore, is simple; if you're trading after-hours, you're trading risky. You're not trading based on what the market's actually doing, you're trading based on what you think the market will do in the morning, and there's still more math going on every second in the privately-held supercomputers in rented cubes in the NYSE basement than you could do all night, digesting this news and projecting what it's going to do to the stocks. Now, if you've done your homework and the stock looks like a good long-term buy, with or without any after-hours news, then place the order at 3 in the morning; who cares what the stock's gonna do at the opening bell. You're gonna hold that stock for the next ten years, maybe; what it does in 5 seconds of opening turmoil is relatively minor compared to the monthly trends that you should be worrying about.", "title": "" }, { "docid": "532599", "text": "The two answers so far are right, but there's a third factor - for many stocks, there's after hours trading. So the official 4PM close is not what the stock's last trade was when they open again. Regardless, even that after hour price is not the starting point as Muro points out.", "title": "" }, { "docid": "255396", "text": "Unless you have a lot of money to get rid of you should spend at least a year trading with a dummy account. It takes a long time to work out what is gong on and your training will get very expensive if you start using real money. Don't start trading with real money until you : Have a strategy. Never trade on a whim. Only trade if your strategy says it is time to trade. Are able to stick to that strategy. It is amazing how easy it is to stray from your strategy just because you feel it is right or you have to try to make up some losses. You will lose money doing this. You are making significant profits for at least 6 months using 1. and 2. with your dummy account. Even after all this, you will probably still lose money. Make sure you only trade with money you can afford to lose. ie. Never trade with this months rent money.", "title": "" }, { "docid": "467463", "text": "Typically the settlement price for a financial instrument (such as AAPL stock) underlying a derivative contract is determined from the average price of trading in that instrument during some short time window specified by the exchange offering the derivative. (Read the fine print on your contract to learn the exact date and time of that settlement period.) Because it's in an exchange's best interest to appear as fair as possible, the exchange will in general pick a high-volume period of time -- such as the close of trading on the expiry date -- in which to determine the settlement price. Now, the expiry date/time may be different from the last time at which the option can be traded, which may be different from the underlying settlement time. For example, most US equity options currently expire on the Saturday following the third Friday of the month, whereas they can last be traded at end-of-day on the third Friday of the month, and the settlement period may be at a slightly different time on the third Friday of the month. (Again, read the contract to know for sure.) Moreover, your broker may demand to know whether you plan to exercise the option at an even earlier date/time. So, to answer your question: After-hours trading can only affect the settlement price of an underlying instrument if the exchange in question decides that the settlement period should happen during after-hours trading. But since no exchange that wants to stay in business would possibly do that, the answer is no. Contract expiry time, contract exercise time, final contract trading time, and underlying settlement time may all fall at different dates/times. The important one for your question is settlement time.", "title": "" }, { "docid": "131117", "text": "Disclaimer: I don't work in the finance industry, and simply took a few classes in corporate finance and management during my undergrad. It depends on what type of investing you're talking about. If you're talking about building a portfolio of securities, then CAPM is the basis for most valuation models. Generally, CAPM will have you discount based on your best available risk-free rate (usually t-bills or some other fixed income source with a reliable backer). Even after your valuation, the basic theory of risk management for an investment portfolio is still to maintain a diverse basket of poorly correlated products. If you're talking about corporate finance where a firm is considering an investment such as a new project, then a determining a WACC and using it as a discount rate for your cash flow is a basic strategy. This is a basic strategy, but there are better ones depending on the specifics of the investment. This is where evaluating exposures is important. To hedge counterparty risk, you might discount by the estimated probability of non-payment or buy trade insurance. To hedge currency risk, you might buy forwards, options, or look into a money market hedge. To hedge political risks like repatriation or changes in tax laws or regulation you might buy political risk insurance. To hedge exposure to a particular commodity price, you can trade futures.", "title": "" }, { "docid": "576632", "text": "\"If I really understood it, you bet that a quote/currency/stock market/anything will rise or fall within a period of time. So, what is the relationship with trading ? I see no trading at all since I don't buy or sell quotes. You are not betting as in \"\"betting on the outcome of an horse race\"\" where the money of the participants is redistributed to the winners of the bet. You are betting on the price movement of a security. To do that you have to buy/sell the option that will give you the profit or the loss. In your case, you would be buying or selling an option, which is a financial contract. That's trading. Then, since anyone should have the same technic (call when a currency rises and put when it falls)[...] How can you know what will be the future rate of exchange of currencies? It's not because the price went up for the last minutes/hours/days/months/years that it will continue like that. Because of that everyone won't have the same strategy. Also, not everyone is using currencies to speculate, there are firms with real needs that affect the market too, like importers and exporters, they will use financial products to protect themselves from Forex rates, not to make profits from them. [...] how the brokers (websites) can make money ? The broker (or bank) will either: I'm really afraid to bet because I think that they can bankrupt at any time! Are my fears correct ? There is always a probability that a company can go bankrupt. But that's can be very low probability. Brokers are usually not taking risks and are just being intermediaries in financial transactions (but sometime their computer systems have troubles.....), thanks to that, they are not likely to go bankrupt you after you buy your option. Also, they are regulated to insure that they are solid. Last thing, if you fear losing money, don't trade. If you do trade, only play with money you can afford to lose as you are likely to lose some (maybe all) money in the process.\"", "title": "" }, { "docid": "241059", "text": "\"NASDAQ has Pre and After market : NASDAQ Trading Schedule Regular Trading Session Schedule The NASDAQ Stock Market Trading Sessions (Eastern Time) Pre-Market Trading Hours from 4:00 a.m. to 9:30 a.m. Market Hours from 9:30 a.m. to 4:00 p.m. After-Market Hours from 4:00 p.m. to 8:00 p.m. Quote and order-entry from 4:00 a.m. to 8:00 p.m. Quotes are open and firm from 4:00 a.m. to 8:00 p.m. You can trade in Pre/After Market but liquidity is very low. If an \"\"unexpected world events\"\" occurs, the volume/liquidity will most certainly increase. Another example is the Forex Market that's open 24/7 around the world. As one major forex market closes, another one opens. According to GMT, for instance, forex trading hours move around the world like this: available in New York between 01:00 pm – 10:00 pm GMT; at 10:00 pm GMT Sydney comes online; Tokyo opens at 00:00 am and closes at 9:00 am GMT; and to complete the loop, London opens at 8:00 am and closes at 05:00 pm GMT. This enables traders and brokers worldwide, together with the participation of the central banks from all continents, to trade online 24 hours a day. src\"", "title": "" }, { "docid": "106817", "text": "1. It is difficult. There is no formal process outside of undergrad and MBA programs to easily gain access to interviews. At your level, its mostly about connections. If willing to start near bottom, go to your business school and start applying to bank associate programs. Sounds like you would like sales and trading more than M&A, so focus there. 2. If you got in at associate level, you would do 1-3 months of training and then get assigned a desk. Finance going through a tough time right now, so trajectory isn't what it used to be. Expect to be a VP after 2-4 years, then its all dependent on luck and skill. 3. If you land a job at a top 15 bank, you should be making total comp of 150k or more after the first year. Salaries not quite at 150k, but most VPS make over 150k salary, not to mention bigger bonus's. 4. If you did M&A you would be working very serious hours. If you go into Sales and Trading your hours will be anywhere from 40 to 60 hours a week depending on the desk. Trading hours tend to be the shortest. 5. Boston isn't a hot bed for i-banking finance. NYC, London, Sing, Hong Kong tend to be the places to be. I know nobody in Boston that could help.", "title": "" }, { "docid": "360059", "text": "\"There are people (well, companies) who make money doing roughly what you describe, but not exactly. They're called \"\"market makers\"\". Their value for X% is somewhere on the scale of 1% (that is to say: a scale at which almost everything is \"\"volatile\"\"), but they use leverage, shorting and hedging to complicate things to the point where it's nothing like a simple as making a 1% profit every time they trade. Their actions tend to reduce volatility and increase liquidity. The reason you can't do this is that you don't have enough capital to do what market makers do, and you don't receive any advantages that the exchange might offer to official market makers in return for them contracting to always make both buy bids and sell offers (at different prices, hence the \"\"bid-offer spread\"\"). They have to be able to cover large short-term losses on individual stocks, but when the stock doesn't move too much they do make profits from the spread. The reason you can't just buy a lot of volatile stocks \"\"assuming I don't make too many poor choices\"\", is that the reason the stocks are volatile is that nobody knows which ones are the good choices and which ones are the poor choices. So if you buy volatile stocks then you will buy a bunch of losers, so what's your strategy for ensuring there aren't \"\"too many\"\"? Supposing that you're going to hold 10 stocks, with 10% of your money in each, what do you do the first time all 10 of them fall the day after you bought them? Or maybe not all 10, but suppose 75% of your holdings give no impression that they're going to hit your target any time soon. Do you just sit tight and stop trading until one of them hits your X% target (in which case you start to look a little bit more like a long-term investor after all), or are you tempted to change your strategy as the months and years roll by? If you will eventually sell things at a loss to make cash available for new trades, then you cannot assess your strategy \"\"as if\"\" you always make an X% gain, since that isn't true. If you don't ever sell at a loss, then you'll inevitably sometimes have no cash to trade with through picking losers. The big practical question then is when that state of affairs persists, for how long, and whether it's in force when you want to spend the money on something other than investing. So sure, if you used a short-term time machine to know in advance which volatile stocks are the good ones today, then it would be more profitable to day-trade those than it would be to invest for the long term. Investing on the assumption that you'll only pick short-term winners is basically the same as assuming you have that time machine ;-) There are various strategies for analysing the market and trying to find ways to more modestly do what market makers do, which is to take profit from the inherent volatility of the market. The simple strategy you describe isn't complete and cannot be assessed since you don't say how to decide what to buy, but the selling strategy \"\"sell as soon as I've made X% but not otherwise\"\" can certainly be improved. If you're keen you can test a give strategy for yourself using historical share price data (or current share price data: run an imaginary account and see how you're doing in 12 months). When using historical data you have to be realistic about how you'd choose what stocks to buy each day, or else you're just cheating at solitaire. When using current data you have to beware that there might not be a major market slump in the next 12 months, in which case you won't know how your strategy performs under conditions that it inevitably will meet eventually if you run it for real. You also have to be sure in either case to factor in the transaction costs you'd be paying, and the fact that you're buying at the offer price and selling at the bid price, you can't trade at the headline mid-market price. Finally, you have to consider that to do pure technical analysis as an individual, you are in effect competing against a bank that's camped on top of the exchange to get fastest possible access to trade, it has a supercomputer and a team of whizz-kids, and it's trying to find and extract the same opportunities you are. This is not to say the plucky underdog can't do well, but there are systematic reasons not to just assume you will. So folks investing for their retirement generally prefer a low-risk strategy that plays the averages and settles for taking long-term trends.\"", "title": "" }, { "docid": "251300", "text": "The answer is to your question is somewhat complicated. You will be unable to compete with the firms traditionally associated with High Frequency Trading in any of their strategies. Most of these strategies which involve marketing making, latency arbitrage, and rebate collection. The amount of engineering required to build the infrastructure required to run this at scale makes it something which can only be undertaken by a team of highly skilled engineers. Indeed, the advantage of firms competing in this space such as TradeBot, TradeWorx, and Getco comes from this infrastructure as most of the strategies that are developed are necessarily simple due to the latency requirements. Now if you expand the definition of HFT to include all computerized automated trading you most certainly can build strategies that are profitable. It is not something that you probably want to tackle on your own but I know of a couple of people that did go it alone successfully for a couple of years before joining an established firm to run a book for them. In order to be successful you will most likely need to develop a unique strategies. The good news is because that you are trying to deploy a very tiny amount of capital you can engage in trades that larger firms would not because the strategies cannot hold enough capital relative to the firms capital base. I am the co-founder of a small trading firm that successfully trades the US Equities and Equity Derivatives markets. A couple of things to note is that if you want to do this you should consider building a real business. Having some more smart brains around you will help. You don't need exchange colocation for all strategies. Many firms, including ours, colocate in a data center that simply has proximity to the exchanges data centers. You will need to keep things simple to be effective. Don't except all the group think that this is impossible. It is possible although as a single individual it will be more difficult. It will require long, long hours as you climb the algorithmic trading learning curve. Good luck.", "title": "" }, { "docid": "414036", "text": "\"During market hours, there are a lot of dealers offering to buy and sell all exchange traded stocks. Dealers don't actually care about the company's fundamentals and they set their prices purely based on order flow. If more people start to buy than sell, the dealer notices his inventory going down and starts upping the price (both his bid and ask). There are also traders who may not be \"\"dealers\"\", but are willing to sell if the price goes high enough or buy if the price goes low enough. This keeps the prices humming along smoothly. During normal trading hours, if you buy something and turn around and sell it two minutes later, you'll probably be losing a couple cents per share. Outside normal market hours, the dealers who continue to have a bid and ask listed know that they don't have access to good price information -- there isn't a liquid market of continuous buying and selling for the dealer to set prices he considers safe. So what does he do? He widens the spread. He doesn't know what the market will open tomorrow at and doesn't know if he'll be able to react quickly to news. So instead of bidding $34.48 and offering at $34.52, he'll move that out to $33 and $36. The dealer still makes money sometimes off this because maybe some trader realized that he has options expiring tomorrow, or a short position that he's going to get a margin call on, or some kind of event that pretty much forces him to trade. Or maybe he's just panicking and overreacting to some news. So why not trade after hours? Because there's no liquidity, and trading when there's no liquidity costs you a lot.\"", "title": "" }, { "docid": "177424", "text": "\"No, a jump in market capitalization does not equal the amount that has been invested. Market cap is simply the stock price times the total number of shares. This represents a theoretical value of the company. I say \"\"theoretical\"\" because the company might not be able to be sold for that at all. The quoted stock price is simply what the last buyer and seller of stock agreed upon for the price of their trade. They really only represent themselves; other investors may decide that the stock is worth more or less than that. The stock price can move on very little volume. In this case, Amazon had released a very good earnings report after the bell yesterday, and the price jumped in after hours trading. The stock price is up, but that simply means that the few shares traded overnight sold for much higher than the closing price yesterday. After the market opens today and many more shares are traded, we'll get a better idea what large numbers of investors feel about the price. But no matter what the price does, the change in market cap does not equal the amount of new money being invested in the company. Market cap is the price of the most recent trades extrapolated out across all the shares.\"", "title": "" }, { "docid": "481298", "text": "Stop orders and stop limit orders typically do not execute during extended hours after the general market session has closed. Stop orders are market orders and market orders especially are not executed during extended hours. Although there are exceptions because a broker can say one thing and do another thing with the way order types are presented to customers vs what their programming actually does. The regulatory burden is a slap on the wrist, so you need to ask the broker what their practices are. Orders created during normal market hours do not execute in extended sessions, different orders would have to be made during the extended session. Your stop order should execute if the normal market hour price stays below your stop price. So a stop limit would actually be worse here, because a stop limit will create a limit order which may never get hit (since it is above the best bid best ask)", "title": "" }, { "docid": "498014", "text": "It looks like GOOG did not have a pre-market trade until 7:14 am ET, so Google Finance was still reporting the last trade it had, which was in the after-hours session yesterday. FB, on the other hand, was trading like crazy after-hours yesterday and pre-market today as it had an earnings report yesterday.", "title": "" }, { "docid": "355548", "text": "As a futures trader, I can tell you that the highs and lows for the ES futures diverge simply because they trade around the clock, from 6PM ET to 5PM ET the next day. The SPX is only open during market hours, as is the SPY, but the SPY also trades in the extended hours sessions for about 3.5 hours before and after the regular hours of 930 AM ET to 4PM ET ET. So bottom line, while they pretty much track each other, the difference in their trading hours results in the highs and lows being different.", "title": "" }, { "docid": "265365", "text": "There are several reasons it is not recommended to trade stocks pre- or post-market, meaning outside of RTH (regular trading hours). Since your question is not very detailed I have to assume you trade with a time horizon of at least more than a day, meaning you do not trade intra-day. If this is true, all of the above points are a non-issue for you and a different set of points becomes important. As a general rule, using (3) is the safest regardless of what and how you trade because you get price guarantee in trade for execution guarantee. In the case of mid to longer term trading (1 week+) any of those points is viable, depending on how you want to do things, what your style is and what is the most comfortable for you. A few remarks though: (2) are market orders, so if the open is quite the ride and you are in the back of the execution queue, you can get significant slippage. (1) may require (live) data of the post-market session, which is often not easy to come by for the entire US stock universe. Depending on your physical execution method (phone, fax, online), you may lack accurate information of the post-market. If you want to execute orders based on RTH and only want to do that after hours because of personal schedule constraints, this is not really important. Personally I would always recommend (3), independent of the use case because it allows you more control over your orders and their fills. TL;DR: If you are trading long-term it does not really matter. If you go down to the intra-day level of holding time, it becomes relevant.", "title": "" }, { "docid": "57520", "text": "Pre-Market trading activity is shown on the site from 4:15 - 9:30 AM (actual trading starts at 4:00 AM EST) The NASDAQ Stock Market Trading Sessions (Eastern Time) Pre-Market Trading Hours from 4:00 a.m. to 9:30 a.m. Market Hours from 9:30 a.m. to 4:00 p.m. After-Market Hours from 4:00 p.m. to 8:00 p.m. Read more: http://www.nasdaq.com/about/trading-schedule.aspx#ixzz38OtcISrq In this case GOOG did not trade in the Pre-market until that time and FB was.", "title": "" }, { "docid": "378889", "text": "\"Often these types of trades fall into two different categories. An error by broker or exchange. Exchange clearing out part of their books incorrectly is an example. Most exchanges make firms reopen their positions for after market hours. There may have been an issue doing so or exchange could incorrectly cancel positions. I was in the direct feed industry for years and this was a big issue. At the same time the broker can issue a no limit buy on accident (or has software that is prospecting and said software has a bug or written poorly). unscrupulous parties looking to feign an upswing or downswing in market. Let's say you hold 500k shares in a stock that sells for $11. You could possibly buy 100 shares for $13. Trust me you will find a seller. Then you are hoping that people see that trade as a \"\"norm\"\" and trade from there, allowing you to rake in $1M for spending an extra $200 - NOTE this is not normal and an extreme example. This was so common in the early days of NASDAQ after hours that they discontinued using the after hours trades as part of historical information that they keep like daily/yearly high or closing price. The liquidity allows for manipulation. It isn't seen as much now since this has been done a million times but it does still happen.\"", "title": "" }, { "docid": "515579", "text": "If I understand you correctly, you are noticing that a stock's price can change drastically when the time changes from pre-market trading hours to open market hours. This could occur because a much smaller pool of investors make trades during pre-market and after-market hours. When the regular market opens there is a large influx of trades, causing the prices to jump.", "title": "" }, { "docid": "176883", "text": "\"A 'Call' gives you the right, but not the obligation, to buy a stock at a particular price. The price, called the \"\"strike price\"\" is fixed when you buy the option. Let's run through an example - AAPL trades @ $259. You think it's going up over the next year, and you decide to buy the $280 Jan11 call for $12. Here are the details of this trade. Your cost is $1200 as options are traded on 100 shares each. You start to have the potential to make money only as Apple rises above $280 and the option trades \"\"in the money.\"\" It would take a move to $292 for you to break even, but after that, you are making $100 for each dollar it goes higher. At $300, your $1200 would be worth $2000, for example. A 16% move on the stock and a 67% increase on your money. On the other hand, if the stock doesn't rise enough by January 2011, you lose it all. A couple points here - American options are traded at any time. If the stock goes up next week, your $1200 may be worth $1500 and you can sell. If the option is not \"\"in the money\"\" its value is pure time value. There have been claims made that most options expire worthless. This of course is nonsense, you can see there will always be options with a strike below the price of the stock at expiration and those options are \"\"in the money.\"\" Of course, we don't know what those options were traded at. On the other end of this trade is the option seller. If he owns Apple, the sale is called a \"\"covered call\"\" and he is basically saying he's ok if the stock goes up enough that the buyer will get his shares for that price. For him, he knows that he'll get $292 (the $280, plus the option sale of $12) for a stock that is only $259 today. If the stock stays under $280, he just pocketed $12, 4.6% of the stock value, in just 3 months. This is why call writing can be a decent strategy for some investors. Especially if the market goes down, you can think of it as the investor lowering his cost by that $12. This particular strategy works best in a flat to down market. Of course in a fast rising market, the seller misses out on potentially high gains. (I'll call it quits here, just to say a Put is the mirror image, you have the right to sell a stock at a given price. It's the difference similar to shorting a stock as opposed to buying it.) If you have a follow up question - happy to help. EDIT - Apple closed on Jan 21, 2011 at $326.72, the $280 call would have been worth $46.72 vs the purchase price of $12. Nearly 4X return (A 289% gain) in just over 4 months for a stock move of 26%. This is the leverage you can have with options. Any stock could just as easily trade flat to down, and the entire option premium, lost.\"", "title": "" }, { "docid": "69395", "text": "\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"", "title": "" }, { "docid": "448952", "text": "I don't think that the trading volume would impact a broker's ability to find shares to short. You might think that a lot more people are trying to short a stock during regular trading hours than in the pre-market, and that's probably true. But what's also true is that a lot more people are covering their shorts during regular trading hours than in the pre-market. For stocks that have difficulty in finding shares to short, any time someone covers a short is an opportunity for you to enter a short. If you want to short a stock and your broker is rejecting your order because they can't find shares to short, then I would recommend that you continue placing that order throughout the day. You might get lucky and submit one of those orders right after someone else has covered their short and before anyone else can enter a short. I have had success doing this in the past.", "title": "" }, { "docid": "151587", "text": "This is dependent on the broker according to The Options Industry Council. Your broker will specify what they would do upon expiry (or hours before last trade) if you did not indicate your preference. Most likely they will conduct a probabilistic simulation to see whether exercising the contracts may result in margin deficit even after selling the delivered shares under extreme circumstances. In most cases, brokers tend to liquidate the option for you (sell to close) before expiry. I've seen people complain about certain brokers forcing liquidation at terrible bid-ask spreads even though the options are still days to expiry. It is better for you to close the position on your own beforehand. The best brokers would allow margin deficit and let you deposit the required amount of money afterward. Please consult your broker's materials. If you can't find them, use live chat or email tickets.", "title": "" }, { "docid": "376179", "text": "Coolness - It's not only a matter of staying calm when being up or down. You must keep yourself from chasing a stock that appears to be running away. Or from betting all your money that something(like say a crash) will happen tomorrow because that would be great for you. Use your head not your heart. Empathy - You need to understand what other speculators, investors, institutions and algorithms are going to do when there is a new development or technical signal. And why. For publicly traded corporations, fundamentals and technical indicators only have the value that people(and their algorithms) choose to assign to them at that particular moment. And every stock has a different population trading it. There is no rule of thumb. Patience - To trade successfully, you must avoid trading at all costs. Heh. If you can't find any good trade to do, don't open positions in order to meet your targets, buy a new smartphone, or to fight boredom. Diligence - If your strategy relies on tight stops, don't make exceptions. If your strategy relies on position sizing, don't close when you are a few points down. Luck - In the end almost every trade can turn against you very badly. You must prepare for the worst and hope for the best. You can't buy luck, or get luckier, but you can attempt to stack probabilities: diversify, buy options to insure your positions, reduce holding time, avoid known volatility events, etc.", "title": "" }, { "docid": "585447", "text": "Before you go filling your head with useless information as there is way too much stuff out there on the stock market. First ask yourself a few questions: There is going to be a balance between the three... don't kid yourself. After you answer these questions find a trading strategy to get the returns you are looking for. Remember the higher returns you expect... the more time you have to put in. Find a trading strategy you like and that works for you. Ounce you have your strategy then find the stocks or ETF that work for that strategy.... Ignore everything else, it is designed to separate you from your money. Making money in the stock market is easy, don't let the media hype and negative people tell you any different. Find something that works for you and perfect it... stick to it.", "title": "" }, { "docid": "116599", "text": "Well the article did mention that if you continually beat your bookmaker you're likely to get rejected in future which is hilarious, but personally I have actually bet on sports and I've found that it's a fairly easy game to win at if you don't go for bets with huge odds and I don't think I've ever placed a bet where after I lost and said 'what the hell just happened'. I only really bet on rugby and soccer though, so team sports may be a bit less prone to corruption from the bookmakers. I'm not saying I think this is a safe way to do business though, I don't think day trading is either. I think they are both speculation. I just think that sports betting has a lot more for a speculator to work with before they develop a strategy. For instance, I always bet on New Zealand winning a rugby game, their players line up as the top in their respective positions and their game strategy essentially has the rules of the game exploited to the maximum. All of the data on this team based on their past performance is actually applicable to their future performance, skilled players usually continue to be so up till a certain age, skilled coaches who stay in their position mean no variation in team strategy. That makes me feel confident that even though New Zealand might lose a game here or there, that they will continue to be winners, and even though the gains on their wins aren't much, consistently winning with them over time builds up to a nice bit of profit. With day trading in the stock market, so much of the variation in prices is due to non accounting fundamentals, and even though historical data can be useful we know that investor sentiment, secret information, and a myriad of other factors mean that unless you are extremely experienced or have a natural eye for reading markets that most traders will lose. I know developing strategies do work for some people, but I think I've seen it said on this sub a couple times that 'trading strategies work - until they don't.' I only speak as a uni student who has limited research beyond Bloomberg articles etc... but from what I can tell, the majority of day traders lose money eventually, and even with AI, the profits are only noteable when the capital input is extremely high. Sports events can't really be swung by the confidence of supporters, and yes corruption is rampant in sports as with every industry, but at least the data you have tells a fairly good story about where the bets will head in the future.", "title": "" }, { "docid": "234892", "text": "Yes, exactly. VaR is just a single tailed confidence interval. To go from model to strategy, you need to design some kind of indicator (i.e. when to buy and when to short or stay out). In practice, this will look like a large matrix with values ranging from -1 to 1 (corresponding to shorting and holding respectively) for each security and each day (or hour, or minute, or tick, etc.), which you then just multiply with the matrix of the stock returns. The resulting matrix will be your daily returns for each stock, you can then just row sum for daily returns of a portfolio, or calculate a cumulative product for cumulative returns. A simple example of an indicator would be something like a value of 1 when the price of the stock is below the 30 day moving average, and 0 otherwise. You can use a battery of econometric models to design these indicators, but the rest of the strategy design is essentially the same, and it's relatively easy to build a one-size-fits-all back-testing code. I'll try to edit this post later and link a blog that goes through some of the code. Edit: [Here](http://www.signalplot.com/simple-machine-learning-model-trade-spy/) is a post that discusses implementing a simple ML strategy. You can ignore most of the content but if you go through the github, you'll see how the ML model is implemented as a strategy. An even easier example can be found from [the github connected to this post](http://www.signalplot.com/how-to-measure-the-performance-of-a-trading-strategy/), where the author is just using a totally arbitrary signal. As you can see, deriving a signal can be a ton of work, but once you have, actually simulating the strategy can be done in just a few lines of code. Hopefully the author won't mind me linking his page here, but I find his coding style to be very clean and good for educational purposes.", "title": "" } ]
1508	How quickly does short float ratio/percent change?	[ { "docid": "41214", "text": "The short float ratio and percent change are all calculated based on the short interest (the total number of shares shorted). The short interest data for Nasdaq and NYSE stocks is published every two weeks. NasdaqTrader.com shows the exact dates for when short interest is published for Nasdaq stocks, and also says the following: FINRA member firms are required to report their short positions as of settlement on (1) the 15th of each month, or the preceding business day if the 15th is not a business day, and (2) as of settlement on the last business day of the month.* The reports must be filed by the second business day after the reporting settlement date. FINRA compiles the short interest data and provides it for publication on the 8th business day after the reporting settlement date. The NYSE also shows the exact dates for when short interest is published for NYSE stocks, and those dates are exactly the same as for Nasdaq stocks. Since the short interest is only updated once every 2 weeks, there is no way to see real-time updating of the short float and percent change. That information only gets updated once every 2 weeks - after each publication of the short interest.", "title": "" } ]	[ { "docid": "192900", "text": "This is the bird's eye view of how shorting works: When you place an order to sell a stock short, your broker attempts to grab the desired number of shares from any accounts of its other customers and makes them available for you to sell. If no other customers own shares of this stock, then generally you are out of luck (It is more complicated like that in practice, but this is just an overview). Your odds are better if the particular stock has a large float (i.e. a large number of shares that are actually available for trading) and its short ratio is low (which means relatively few shares are currently being sold short). Also, a large brokerage may be more likely to have access to the shares than a small niche-market broker. The example you've given, Angie's List (ANGI) is a $600M small-cap with a comparatively low float, and though I haven't been able to glean the short ratio, it appears that a lot of investors are bearish on this stock and probably already had the same idea to short it. There is really no way to find out if a specific broker has shares in inventory available for shorting, short of (forgive the pun) checking directly with the broker.", "title": "" }, { "docid": "562220", "text": "A value of zero or a negative value makes the percent change meaningless. Saying 100% when going from 0 to some other value is simply wrong. I have seen a similar situation several times when looking at a public company with a loss last quarter. On Google Finance or some other service, the PE ratio will be blank, N/A, or something like that. If the company does not currently have earnings, then the PE ratio is meaningless. Likewise, if the company previously did not have earnings, then the percent change of the earnings is meaningless. Also consider the example where the previous value was negative. If the previous value was negative 1 and the current value is positive 99, then this happens: A negative change? But the value went up! Obviously that value does not make sense and should not be shown.", "title": "" }, { "docid": "589476", "text": "\"In the end, this is really not a finance question. It's about changing one's habits. (One step removed, however, since you are helping a friend and not seeking advice for yourself). I've learned a simple cause & effect question - Does someone who wants (goal here) do (this current bad habit)? For example, someone with weight to lose is about to grab the chips to sit and watch TV. They should quickly ask themselves \"\"Does a healthy, energetic person sit in front of the TV eating chips?\"\" The friend needs to make a connection between the expense he'd like to save up for and his current actions. There's a conscious decision in making the takeout purchase, he'd rather spend the money on that meal than to save .5% (or whatever percent) of the trip's cost. If he is clueless in the kitchen, that opens another discussion, one in which I'd remark that on the short list of things parents should teach their kids, cooking is up there. My wife is clueless in the kitchen, I taught our daughter how to be comfortable enough to make her own meals when she wants or when she's off on her own. If this is truly your friend's issue, you might need to be a cooking spirit guide to be successful.\"", "title": "" }, { "docid": "358997", "text": "What is your time horizon? Over long horizons, you absolutely want to minimise the expense ratio – a seemingly puny 2% fee p.a. can cost you a third of your savings over 35 years. Over short horizons, the cost of trading in and trading out might matter more. A mutual fund might be front-loaded, i.e. charge a fixed initial percentage when you first purchase it. ETFs, traded daily on an exchange just like a stock, don't have that. What you'll pay there is the broker commission, and the bid-ask spread (and possibly any premium/discount the ETF has vis-a-vis the underlying asset value). Another thing to keep in mind is tracking error: how closely does the fond mirror the underlying index it attempts to track? More often than not it works against you. However, not sure there is a systematic difference between ETFs and funds there. Size and age of a fund can matter, indeed - I've had new and smallish ETFs that didn't take off close down, so I had to sell and re-allocate the money. Two more minor aspects: Synthetic ETFs and lending to short sellers. 1) Some ETFs are synthetic, that is, they don't buy all the underlying shares replicating the index, actually owning the shares. Instead, they put the money in the bank and enter a swap with a counter-party, typically an investment bank, that promises to pay them the equivalent return of holding that share portfolio. In this case, you have (implicit) credit exposure to that counter-party - if the index performs well, and they don't pay up, well, tough luck. The ETF was relying on that swap, never really held the shares comprising the index, and won't necessarily cough up the difference. 2) In a similar vein, some (non-synthetic) ETFs hold the shares, but then lend them out to short sellers, earning extra money. This will increase the profit of the ETF provider, and potentially decrease your expense ratio (if they pass some of the profit on, or charge lower fees). So, that's a good thing. In case of an operational screw up, or if the short seller can't fulfil their obligations to return the shares, there is a risk of a loss. These two considerations are not really a factor in normal times (except in improving ETF expense ratios), but during the 2009 meltdown they were floated as things to consider. Mutual funds and ETFs re-invest or pay out dividends. For a given mutual fund, you might be able to choose, while ETFs typically are of one type or the other. Not sure how tax treatment differs there, though, sorry (not something I have to deal with in my jurisdiction). As a rule of thumb though, as alex vieux says, for a popular index, ETFs will be cheaper over the long term. Very low cost mutual funds, such as Vanguard, might be competitive though.", "title": "" }, { "docid": "451898", "text": "\"Discussing individual stocks is discouraged here, so I'll make my answer somewhat generic. Keep in mind, some companies go public in a way that takes the shares that are held by the investment VCs (venture capitalists) and cashes them out of their positions, i.e. most if not all shares are made public. In that case, the day after IPO, the original investors have their money, and, short of the risk of being sued for fraud, could not care less what the stock does. Other companies float a small portion up front, and retain the rest. This is a way of creating a market and valuing the company, but not floating so many shares the market has trouble absorbing it. This stock has a \"\"Shares Outstanding\"\" of 2.74B but has only floated 757.21M. The nearly 2 billion shares held by the original investors certainly impact their wallets with how this IPO went. See the key statistics for the details.\"", "title": "" }, { "docid": "419397", "text": "\"TBF - Proshares short 20+ Year Treasury The TBF fund is designed to track (hopefully) 100 percent of the inverse daily returns of the Barclays Capital 20+ Year U.S. Treasury Index. there's some risk of tracking error, and also a compounding effect if it's down several days in a row. (invest with care) There's also a TBT fund, but the risks are even greater since it is leveraged, potentially you could make the right long term call, but lose a lot in the short term due to tracking error and effect of compounding) (that would tend to make this one more appropriate for short term 'bets' on interest rates, and less so for a long term investor) There are also quite a few floating rate closed-end funds (Click here, then click on \"\"loan participation funds\"\") that should do well in a rising rate environment. Just beware that these funds seem to incorporate a substantial amount of credit risk as well as floating interest rate exposure. Closed end funds trade a lot like securities, since the fund is closed, you have to buy shares from another owner that is selling (just like with stocks), that means the shares can sometimes trade above or below the underlying value of the actual assets held by the fund depending on buying/selling pressure and the relative liquidity of a given fund.\"", "title": "" }, { "docid": "295511", "text": "When you buy a stock, the worst case scenario is that it drops to 0. Therefore, the most you can lose when buying a stock is 100% of your investment. When you short a stock, however, there's no limit on how high the stock can go. If you short a stock at 10, and it goes up to 30, then you've lost 200% on your investment. Therefore shorting stocks is riskier than buying stocks, since you can lose more than 100% of your investment when shorting. because the price might go up, but it will never be as big of a change as a regular price drop i suppose... That is not true. Stocks can sometimes go up significantly (50-100% or more) in a very short amount of time on a positive news release (such as an earnings or a buyout announcement). A famous example occurred in 2008, when Volkswagen stock quintupled (went up 400%) in less than 2 days on some corporate news: Porsche, for some reason, wants to control Volkswagen, and by building up its stake has driven up the price. Hedge funds, figuring the share price would fall as soon as Porsche got control and stopped buying, sold a lot of VW shares short. Then last weekend, Porsche disclosed that it owned 42.6 percent of the stock and had acquired options for another 31.5 percent. It said it wanted to go to 75 percent. The result: instant short-squeeze. The German state of Lower Saxony owns a 20 percent stake in VW, which it said it would not sell. That left precious few shares available for anyone else. The shorts scrambled to cover, and the price leaped from about €200, or about $265, to above €1,000.", "title": "" }, { "docid": "133204", "text": "\"Probably the biggest driver of the increased volumes that day was a change in sentiment towards the healthcare sector as a whole that caused many healthcare companies to experience higher volumes ( https://www.bloomberg.com/press-releases/2017-07-11/asset-acquisitions-accelerate-in-healthcare-sector-boosting-potential-revenue-growth ). Following any spike, not just sentiment related spikes, the market tends to bounce back to about where it had been previously as analysts at the investment banks start to see the stock(s) as being overbought or oversold. This is because the effect of a spike on underlying ratios such as the Sharpe ratio or the PE ratio makes the stock look less attractive to buyers and more attractive to sellers, including short sellers. Note, however, that the price is broadly still a little higher than it was before the spike as a result of this change in sentiment. Looking at the price trends on Bloomberg (https://www.bloomberg.com/quote/CDNA:US) the price had been steadily falling for the year prior to the spike but was levelling out at just over $1 in the few months immediately prior to the spike. The increased interest in the sector and the stock likely added to a general change in the direction of the price trend and caused traders (as opposed to investors) to believe that there was a change in the price trend. This will have lead to them trading the stock more heavily intraday exacerbating the spike. Note that there traders will include HFT bots as well as human traders. You question the legality of this volume increase but the simple answer is that we may never know if it was the target of traders manipulating the price or a case of insider trading. What we can see is that (taking \"\"animal spirits\"\" into account) without any evidence of illegality there are plenty of potential reasons why the spike may have occurred. Spikes are common where traders perceive a change in a trend as they rush to cash in on the change before other traders can and then sell out quickly when they realise that the price is fundamentally out of sync with the firm's underlying position. You yourself say that you have been watching the stock for some time and, by that fact alone, it is likely that others are for the same reasons that you are. Otherwise you wouldn't be looking at it. Where people are looking at a stock expecting it to take off or drop you expect volatility and volatility means spikes!\"", "title": "" }, { "docid": "516214", "text": "\"TL;DR - go with something like Barry Ritholtz's All Century Portfolio: 20 percent total U.S stock market 5 percent U.S. REITs 5 percent U.S. small cap value 15 percent Pacific equities 15 percent European equities 10 percent U.S. TIPs 10 percent U.S. high yield corp bonds 20 percent U.S. total bond UK property market are absurdly high and will be crashing a lot very soon The price to rent ratio is certainly very high in the UK. According to this article, it takes 48 years of rent to pay for the same apartment in London. That sounds like a terrible deal to me. I have no idea about where prices will go in the future, but I wouldn't voluntarily buy in that market. I'm hesitant to invest in stocks for the fear of losing everything A stock index fund is a collection of stocks. For example the S&P 500 index fund is a collection of the largest 500 US public companies (Apple, Google, Shell, Ford, etc.). If you buy the S&P 500 index, the 500 largest US companies would have to go bankrupt for you to \"\"lose everything\"\" - there would have to be a zombie apocalypse. He's trying to get me to invest in Gold and Silver (but mostly silver), but I neither know anything about gold or silver, nor know anyone who takes this approach. This is what Jeremy Siegel said about gold in late 2013: \"\"I’m not enthusiastic about gold because I think gold is priced for either hyperinflation or the end of the world.\"\" Barry Ritholtz also speaks much wisdom about gold. In short, don't buy it and stop listening to your friend. Is buying a property now with the intention of selling it in a couple of years for profit (and repeat until I have substantial amount to invest in something big) a bad idea? If the home price does not appreciate, will this approach save you or lose you money? In other words, would it be profitable to substitute your rent payment for a mortgage payment? If not, you will be speculating, not investing. Here's an articles that discusses the difference between speculating and investing. I don't recommend speculating.\"", "title": "" }, { "docid": "163904", "text": "\"The answers here are all correct. This is 100% scam, beyond any reasonable doubt. Don't fall for it. However, I felt it valuable to explain what would happen were you to fall for this. It's not all that hard to understand, but it involves understanding some of the time delays that exist in modern banking today. The most important thing to understand is that depositing a check does not actually put dollars in your account, even though it appears to. A check is not legal tender for debts public and private. It's a piece of paper known as a \"\"bill of exchange.\"\" It's an authorization for a payee (you), to request that their bank pay you the amount on the check. A transaction made with a check does not actually draw to a close until your bank and their bank communicate and cause the actual transfer of funds to take place. This process is called \"\"clearing\"\" the check. Despite living in the modern times, this process is slow. It can take 7-10 days to clear a check (especially if it is an international bank). This is not good for the banking business. You can imagine how difficult it would be to tell a poor client, who is living paycheck to paycheck, that he can't have his pay until the check clears a week later. Banks have an interest in hiding this annoying feature of the modern banking system, so they do. When you deposit a check, the bank will typically advance you the money (an interest free loan, in effect) while the check \"\"floats\"\" (i.e. until it clears). This creates the illusion that the money is actually in your account for most intents and purposes. (presumably a bank would distinguish between the floating check and a cleared check if you tried to close out your account, but otherwise it looks and feels like the money is in your hands). Of course, if the check is dishonored (because the payer had insufficient funds, or the account simply did not exist), your bank will not get the money. At this moment, they will cancel any advances you received and notify you that the check bounced. Again, this happens 7-10 days later. The general pattern of this scam is that they will pay you by a method which clears slowly, like a check. They will then ask you to withdraw the money using a faster clearing method (like a wire transfer or withdrawing the cash). Typically they will be encouraging you to move quickly (they are on a timetable... when their check bounces, the game is up!) At this time, it will appear as though the account has a positive balance, but in fact it has a negative balance plus an advance on the check. This looks great until 7-10 days later, when the check bounces. At that time, the bank will cancel the advance, and reality will set in. You will now have an open bank account, legally opened by you in your own name, which is deeply in debt. Meanwhile, the scammer walks away with all the money that you sent them (which cleared quickly). There are many variants which can hide the details. Some can play games with check kiting to try to make your first check clear (then try to rope you in for a more painful hit). Some will change the instruments they use (checks are the easy ones, so they're simply most common). Don't try to think \"\"maybe this one is legit.\"\" These scammers literally make a living off of making shady transactions look legit. Things I would recommend looking out for:\"", "title": "" }, { "docid": "180404", "text": "\"Intrinsic value is a myth. There is no such thing. Subjective human demand is the only thing that gives anything value. This subjectivity is different person to person and can change very quickly. Historically there are two main uses for gold: jewelry and money. How can you tell when a particular type of money is undervalued? It disappears from circulation since people prefer to use money that is overvalued. This phenomenon is paraphrased in Gresham's Law: Bad money drives out good money. The Coinage Act of 1792 established the US dollar as 371.25 grains of silver or 24.75 grains of gold. This established a government ratio of 15 ounces of silver to 1 ounce of gold. In the late 18th century there was a large production of silver from Mexico and the market ratio of silver to gold increased to 15.75 to 1 by 1805. The government ratio, however, was still 15 to 1. This was enough incentive for people to exchange their silver coins for gold coins at the government ratio, melt the gold, and sell the gold bullion overseas at the market value. Thus, gold coins disappeared from circulation as people either hoarded the gold or sent it abroad. People used the overvalued silver coins (i.e. the \"\"bad\"\" money) domestically and gold coins disappeared from the market. In an attempt to correct the problem of disappearing gold coins the Coinage Act of 1834 was enacted. It kept the US dollar at 371.25 grains of silver but changed the definition to 23.2 grains of gold which established a government ratio of 16 to 1. This was close to the market ratio of gold to silver at the time so both gold and silver coins appeared in circulation again. The gold rush of 1849 produced a lot of gold and the market ratio of silver to gold became 15.46 to 1. Now gold was overvalued so people began exchanging their gold coins for silver coins at the government ratio, melt the silver, and sell the silver bullion overseas at the market value. People used the overvalued gold coins (i.e. the \"\"bad\"\" money) domestically and silver coins disappeared from the market. When you see gold circulating everywhere you will know it is overvalued compared to other types of money. Paper money always drives gold out of circulation since the market ratio of paper to gold severely under values gold. Source here.\"", "title": "" }, { "docid": "459257", "text": "I am going to break rank slightly with the consensus so far. Here's the deal, it probably DOES help your credit slightly to pay it multiple times per month if it isn't a hassle, but the bump is likely to be minimal and very temporary. Here's why: A key component of your score is your credit usage ratio. That is the ratio of how much of your credit limits you are using. You want to keep this number down as low as possible. Now here is where it gets tricky. Although you have a grace period to pay off your card with no interest, the credit card companies don't generally report the balance as of the due date. They either report the high balance or an average balance over the month. That is, it is based on how much you use, not how much balance you carry over each month. It isn't very intuitive, but that's just how it is. So technically, keeping that balance lower over the course of the month WILL probably help you, but the credit usage ratio is generally a rolling average over the last x months, so the effect will wear off quickly. So it is probably not worth doing unless you know you are going to apply for a loan in the next 6 months and need a temporary, small bump. Another consideration is that paying early provides no real financial benefit in terms of finance charges, but you are giving up liquidity which does have some value. 1) You probably could get at least a little interest for keeping the money in your account a few more weeks. 2) If you have a major financial emergency, e.g. broken down car, you might appreciate the fact that you kept your options open to carry that balance over a month.", "title": "" }, { "docid": "296420", "text": "It depends a lot on your investment period and the quality of the bonds that you want to invest. For example, if you want to invest until the maturity of the bonds, and the bonds are very safe (i.e. they are not expected to default), it does not matter that the interest rate rise. That is because at the maturity of the bond it will converge to its maturity value which will be independent of the change of the interest rates (although on the middle of the life the price of the bond will go down, but the coupon should remain constant -unless is a floating coupon bond-). An option could be to invest in an ETF with short term bonds (e.g. 1 year) with AAA credit rating (high quality, so very low default rate). It won't yield much, but is more than 0% if you hold it until maturity.", "title": "" }, { "docid": "499849", "text": "\"They're taking advantage of float. Like so many things in the financial world today, this practice is a (strictly legal) fraud. When you make the transaction, the money is available immediately, for reasons that should be intuitively obvious to anyone who's ever used PayPal. It doesn't take 3 minutes for the broker to get that money, let alone 3 days. But if they can hold on to that money instead of turning it over to you, they can make money from it for themselves, putting money that rightfully belongs to you to work for them instead, earning interest on short-term loans, money market accounts, etc. The SEC mandates that this money must be turned over to you within 3 days so it should not surprise anyone that that's exactly how long the \"\"we have to wait for it to clear\"\" scam runs for. Even if it doesn't seem like very much money per transaction, for a large brokerage with hundreds of thousands of clients, all the little bits add up very quickly. This is why they feel no need to compete by offering better service: offering poor service is making them a lot of money that they would lose by offering better service.\"", "title": "" }, { "docid": "497530", "text": "When property changes hands the sale prices may or may not be used to determine the appraised value of the property, and they may or may not be used to determine the appraised value of other properties. Because of the nature of the transaction: you already have an existing business relationship, the local government is likely to ignore the data point provided by your transaction when determining values of similar properties. They have no idea if there was some other factor used to determine the price. They will also not include in the calculation transactions that are a result of foreclosure becasue the target price is the loan value not the true value. California and some other jurisdictions do add another wrinkle. You will need to determine if the transaction will trigger a reevaluation of the property value. In some states the existing laws of the state limited the annual growth of the assessment, but that could now be recaptured if the jurisdiction rules that this is a new ownership: California Board of Equalization - Change in Ownership - Frequently Asked Questions How does a change in ownership affect property taxes? Each county assessor's office reviews all recorded deeds for that county to determine which properties require reappraisal under the law. The county assessors may also discover changes in ownership through other means, such as taxpayer self-reporting, field inspections, review of building permits and newspapers. Once the county assessor has determined that a change in ownership has occurred, Proposition 13 requires the county assessor to reassess the property to its current fair market value as of the date ownership changed. Since property taxes are based on the assessed value of a property at the time of acquisition, a current market value that is higher than the previously assessed Proposition 13 adjusted base year value will increase the property taxes. Conversely, if the current market value is lower than the previously assessed Proposition 13 adjusted base year value, then the property taxes on that property will decrease. Only that portion of the property that changes ownership, however, is subject to reappraisal. For example, if 50 percent of the property is transferred, the assessor will reassess only 50 percent of the property at its current fair market value as of the date of the transfer, and deduct 50 percent from any existing Proposition 13 base year value. In most cases, when a person buys a residence, the entire property undergoes a change in ownership and 100 percent of the property is reassessed to its current market value.", "title": "" }, { "docid": "351925", "text": "\"1 - in most cases, the difference between filing joint or married filing single is close to zero. When there is a difference you're better off filing joint. 2 - The way the W4 works is based on how many allowances you claim. Unfortunately, even in the day of computers, it does not allow for a simple \"\"well my deduction are $xxx, don't tax that money.\"\" Each allowance is equal to one exemption, same as you get for being you, same as the wife gets, same as each kid. 3 people X $3800 = $11,400 you are telling the employer to take off the top before calculating your tax. She does this by using Circular E and is able to calculate your tax as you request. If one is in the 15% bracket, one more exemption changes the tax withheld by $570. So if you were going to owe $400 in April, one few exemption will have you overpay $170. i.e. in this 15% bracket, each exemption changes annual withholding by that $570. For most people, running the W4 numbers will get them very close, and only if they are getting back or owing over $500, will they even think of adjusting. 3 - My recently published Last Minute Tax Moves offers a number of interesting ideas to address this. The concept of grouping deductions in odd years is worth noting. 4 - I'm not sure what this means, 2 accounts each worth $5000 should grow at the same rate if invested the same. The time it makes sense to load one person's account first is if they have better matching. You say you are not sure what percent your wife's company matches. You need to change this. For both of your retirement plans you need to know every detail, exact way to maximize matching, expense ratios for the investments you choose, any other fees, etc. Knowledge is power, and all that. In What is an appropriate level of 401k fees or expenses in a typical plan? I go on to preach about how fees can wipe out any tax benefit over time. For any new investor, my first warning is always to understand what you are getting into. If you can't explain it to a friend, you shouldn't be in it. Edit - you first need to understand what choices are within the accounts. The 4% and 6% are in hindsight, right? These are not fixed returns. You should look at the choices and more heavily fund the account with the better selection. Deposit to her account at least to grab the match. As far as the longer term goals, see how the house purchase goes. Life has a way of sending you two kids and forcing you to tighten the budget. You may have other ideas in three years. (I have no P2P lending experience, by the way.) Last - many advise that separate finances are a bad path for a couple. It depends. Jane and I have separate check books, and every paycheck just keep enough to write small checks without worry, most of the money goes to the house account. Whatever works for you is what you should do. We've been happily married for most of the 17 years we've been married.\"", "title": "" }, { "docid": "45523", "text": "Most bond ETFs have switched to monthly dividends paid on the first of each month, in an attempt to standardize across the market. For ETFs (but perhaps not bond mutual funds, as suggested in the above answer) interest does accrue in the NAV, so the price of the fund does drop on ex-date by an amount equal to the dividend paid. A great example of this dynamic can be seen in FLOT, a bond ETF holding floating rate corporate bonds. As you can see in this screenshot, the NAV has followed a sharp up and down pattern, almost like the teeth of a saw. This is explained by interest accruing in the NAV over the course of each month, until it is paid out in a dividend, dropping the NAV sharply in one day. The effect has been particularly pronounced recently because the floating coupon payments have increased significantly (benchmark interest rates are higher) and mark-to-market changes in credit spreads of the constituent bonds have been very muted.", "title": "" }, { "docid": "148632", "text": "Also, almost by definition rebalancing involves making more trades than you would have otherwise; wouldn't the additional trading fees you incurred in doing so reduce the benefits of this strategy? You forgot to mention taxes. Rebalancing does or rather can incur costs. One way to minimize the costs is to use the parts of the portfolio that have essentially zero cost of moving. These generally are the funds in your retirement accounts. In the United States they can be in IRAs or 401Ks; they can be regular or Roth. Selling winners withing the structure of the plan doesn't trigger capital gains taxes, and many have funds within them that have zero loads. Another way to reduce trading fees is to only rebalance once a year or once every two years; or by setting a limit on how far out of balance. For example don't rebalance at 61/39 to get back to 60/40 even if it has been two years. Given that the ratio of investments is often rather arbitrary to begin with, how do I know whether I'm selling high and buying low or just obstinately sticking with a losing asset ratio? The ratio used in an example or in an article may be arbitrary, but your desired ratio isn't arbitrary. You selected the ratio of your investments based on several criteria: your age, your time horizon, your goals for the money, how comfortable you are with risk. As these change during your investing career those ratios would also morph. But they aren't arbitrary. These decisions to rebalance are separate from the ones to sell a particular investment. You could sell Computer Company X because of how it is performing, and buy stock in Technology Company Y because you think it has a better chance of growing. That transaction would not be a re-balancing. Selling part of your stock in Domestic Company A to buy stock in international Company B would be part of a re-balancing.", "title": "" }, { "docid": "591461", "text": "\"I recommend you take a look at this lecture (really, the whole series is enlightening), from Swenson. He identifies 3 sources of returns: diversification, timing and selection. He appears to discard timing and selection as impossible. A student kinda calls him out on this. Diversification reduces risk, not increase returns. It turns out they did time the market, by shorting .com's before the bubble, and real estate just before the downturn. In 1990, Yale started a \"\"Absolute Return\"\" unit and allocated like 15 percent to it, mostly by selling US equities, that specializes in these sorts of hedging moves. As for why you might employ managers for specific areas, consider that the expense ratio Wall Street charges you or me still represent a very nice salary when applied to the billions in Yale's portfolio. So they hire internally to reduce expenses, and I'm sure they're kept busy. They also need people to sell off assets to maintain ratios, and figuring out which ones to sell might take specialized knowledge. Finally, in some areas, you functionally cannot invest without management. For example, Yale has a substantial allocation in private equity, and by definition that doesn't trade on the open market. The other thing you should consider is that for all its diversification, Yale lost 25 percent of their portfolio in 2009. For a technique that's supposed to reduce volatility, they seem to have a large range of returns over the past five years.\"", "title": "" }, { "docid": "434279", "text": "\"Here is the \"\"investing for retirement\"\" theoretical background you should have. You should base your investment decisions not simply on the historical return of the fund, but on its potential for future returns and its risk. Past performance does not indicate future results: the past performance is frequently at its best the moment before the bubble pops. While no one knows the specifics of future returns, there are a few types of assets that it's (relatively) safe to make blanket statements about: The future returns of your portfolio will primarily be determined by your asset allocation . The general rules look like: There are a variety of guides out there to help decide your asset allocation and tell you specifically what to do. The other thing that you should consider is the cost of your funds. While it's easy to get lucky enough to make a mutual fund outperform the market in the short term, it's very hard to keep that up for decades on end. Moreover, chasing performance is risky, and expensive. So look at your fund information and locate the expense ratio. If the fund's expense ratio is 1%, that's super-expensive (the stock market's annualized real rate of return is about 4%, so that could be a quarter of your returns). All else being equal, choose the cheap index fund (with an expense ratio closer to 0.1%). Many 401(k) providers only have expensive mutual funds. This is because you're trapped and can't switch to a cheaper fund, so they're free to take lots of your money. If this is the case, deal with it in the short term for the tax benefits, then open a specific type of account called a \"\"rollover IRA\"\" when you change jobs, and move your assets there. Or, if your savings are small enough, just open an IRA (a \"\"traditional IRA\"\" or \"\"Roth IRA\"\") and use those instead. (Or, yell at your HR department, in the event that you think that'll actually accomplish anything.)\"", "title": "" }, { "docid": "192894", "text": "This isn't new. In the mid 80s rules were established by the IRS to differentiate life insurance from Modified Endowment Contracts, placing upper limits on how much money could be placed in life insurance accounts relative to the coverage provided and how quickly (fastest a policy can become paid-in-full is 7 years). None of this closes the fundamental loophole, but it exists for a reason, taxation of life insurance is probably unwise and would result in less people using life insurance as a risk mitigation technique, despite the fact that it's very appropriate for that in some situations. The problem here is that once you get out of everyday-people numbers and into very large sums the vehicle can be clearly abused to avoid taxes on investment gains while living, and possibly avoid them altogether depending on how the estate is structured, and this is bad for the average person who'd like the megarich to pay their percent towards the public needs the same way the average guy does.", "title": "" }, { "docid": "390598", "text": "Since recent changes to credit scoring (July 2017) it may not be necassary to do this, as more emphasis is placed on having a timely payment history and less emphasis is placed on having a low credit utilization ratio. Using what’s known as trended data is the biggest change. The phrase means credit scores will take into account the trajectory of a borrower’s debts on a month-to-month basis. In fact, having a low credit utilization ratio may even negatively effect you (if your available credit line value is high): ... VantageScore will now mark a borrower negatively for having excessively large credit card limits, on the theory that the person could run up a high credit card debt quickly. Those who have prime credit scores may be hurt the most, since they are most likely to have multiple cards open. But those who like to play the credit card rewards program points game could be affected as well. source", "title": "" }, { "docid": "87150", "text": "To point #1: We are moving but I don't know If I can afford the rent as the family grows I would start by looking at your debt-to-income ratio. In the US, most banks look at this for mortgage purposes, but it also gives you a general idea of what monthly mortgage payments will be comfortable given your particular financial situation. Think of it this way, if a bank is unwilling to lend you money because of a high debt-to-income level, this indicates that you have very little leeway with regard to your budget. So a lower number indicates that you will have more flexibility and comfort with meeting your rent/mortgage obligations when unforeseen bills pop up. The article below indicates having < 43% DTI is ideal (in the US). Here's a link to a debt to income calculator and some extra info (I suggest finding one aimed at the UK market): WellsFargo debt to income calculator Why is the 43% debt to income ratio important? Point #2: How can a person measure how much to spend on food, car, bills or rent from his salary? Is there a formula to keep in check? Other answers have addressed how to make a budget, so I will not repeat that. However, here's another angle with regards to spending/saving. This article recommends 50/30/20: According to the popular 50/30/20 rule, you should reserve 50 percent of your budget for essentials like rent and food, 30 percent for discretionary spending, and at least 20 percent for savings. Read more at: https://www.moneyunder30.com/how-much-should-you-save-every-month-2 In the real world, these goals may not be realistic, and different people have different ideas about how aggressive to be with regards to savings. However, you can get a general idea and adapt for your particular needs. Point 3: I find myself looking at my account every single day and get tensed and sad because almost whenever the money (pay) comes in I freak out that after everything there is nothing for us to enjoy or save.", "title": "" }, { "docid": "53637", "text": "\">No, virtually ever item in the CPI is adjusted using hedonics, which by definition can only be used to lower inflation, not adjust it up. Wow. Just wow. Let's analyze this: >virtually ever item in the CPI is adjusted using hedonics How does one apply hedonics to energy? There are so many items in the CPI basket for which this does not even make sense I don't know where to begin with such a blanket statement. [Here is how the BLS computes CPI](http://www.bls.gov/cpi/cpifaq.htm#Question_6). Note the categories, and that they currently track hundreds of goods in each of about 200 categories, totaling tens of thousands of goods. With a little digging you can find the weighting. [Here is the list of what they apply hedonic weights to](http://www.bls.gov/cpi/cpihqaitem.htm). It is a vastly smaller subset of all goods tracked, and the weightings makes them not affect overall CPI much at all. All the precise methodologies are listed on the BLS site, and you can track it all down. As stated below, someone has done the analysis (and there is a PDF on the site) and they obtained that incuding hedonic items affects inflation only by 0.005 percent per year. >which by definition can only be used to lower inflation By your definition? The actual definition does not force either direction. In reality it adjusts up and down as clearly shown in BLS reports, which I'll link below. >, not adjust it up. As I'll list below, it in fact does go both ways. Finally, analysis of hedonics seems to indicate it has a miniscule effect on inflation rates, again papers are cited in the link shown below. [Critics often incorrectly assume that BLS only adjusts for quality increases, not for decreases, and that hedonic adjustments have a large downward impact on the CPI. On the contrary, BLS has used hedonic models in the CPI shelter and apparel components for roughly two decades, and on average hedonic adjustments usually increase the rate of change of those indexes. Since 1998, hedonic models have been introduced in several other components, mostly consumer durables such as personal computers and televisions, but these newer areas have a combined weight of only about one percent in the CPI. A recent article by BLS economists estimated that the hedonic models currently used in the CPI outside of the shelter and apparel areas have increased the annual rate of change of the All Items CPI, but by only about 0.005 percent per year.](http://www.bls.gov/cpi/cpiqa.htm#Question_4). >inflation represents how the value of the dollar has accrued vs the value of a 20\"\" TV, which is what the definition of inflation is. No, inflation must measure the price of the same good over time. When some goods are no longer available, other goods must be investigated to provide continuity in the comparisons. Otherwise you'll have me comparing the price of a horse to the price of a car since they both provide transportation, yet over time one replaces the other, and direct comparisons on $ alone does not accurately measure what one gets for their money. You cannot compare the cost of different goods purely on price alone and call that inflation. >So, no, I don't think you're correct on this. Well, [since other places that track inflation](http://bpp.mit.edu/) arrive at very similar results using different methodologies, and a vastly larger pool of goods I think that you overstate that the changes did not increase accuracy of inflation measurement. >This is also kind of glossing over the fact that the CPI essentially makes the bold argument that energy and transportation prices never affect inflation. CPI makes no such claim. What do you think caused inflation in the early 1970s when oil prices shot up? [Here is the most recent CPI data release from BLS](http://www.bls.gov/news.release/cpi.nr0.htm) which quite clearly shows both energy and transportation changes being reflected in the CPI. I think when you make a claim you should at least look up if it matches the actual data. This is tiring trying to find evidence for/against so many dogmatic beliefs.\"", "title": "" }, { "docid": "377364", "text": "That's easy, keep making the payments and go on with life. The number that matters more than loan/market value is loan/equity. As long as you can sell it for enough to pay the balance on your loan you should be okay. Not saying it doesn't suck, but financially you are fine. If you owe more than the house is worth, I'd suggest paying it down as quickly as possible to fix that ratio to reduce your financial risk in case you lose your source of income. Personally, I think it is pretty slimy for people to walk away from house notes or try to short sell them when they can afford to continue payments just because the market value of the house fell. How would you feel if, when house prices were skyrocketing, the bank canceled your loan and repossessed your house because they could resell it for more money? (not that they could realistically, just speaking hypothetically.)", "title": "" }, { "docid": "524030", "text": "John Bogle never said only buy the S&P 500 or any single index Q:Do you think the average person could safely invest for retirement and other goals without expert advice -- just by indexing? A: Yes, there is a rule of thumb I add to that. You should start out heavily invested in equities. Hold some bond index funds as well as stock index funds. By the time you get closer to retirement or into your retirement, you should have a significant position in bond index funds as well as stock index funds. As we get older, we have less time to recoup. We have more money to protect and our nervousness increases with age. We get a little bit worried about that nest egg when it's large and we have little time to recoup it, so we pay too much attention to the fluctuations in the market, which in the long run mean nothing. How much to pay Q: What's the highest expense ratio that one should pay for a domestic equity fund? A: I'd say three-quarters of 1 percent maybe. Q: For an international fund? A: I'd say three-quarters of 1 percent. Q: For a bond fund? A: One-half of 1 percent. But I'd shave that a little bit. For example, if you can buy a no-load bond fund or a no-load stock fund, you can afford a little more expense ratio, because you're not paying any commission. You've eliminated cost No. 2....", "title": "" }, { "docid": "238130", "text": "because it's not cheaper? it's virtually free to run a private chain (no transaction fees, no competition for mining), it doesn't require even a millionth of a fraction of the maintenance resources, and you maintain total operational control over it (bitcoin could crash, it's encryption could be broken, 100's of things could change which would totally shitbrick your internal infrastructure). lastly, if you want, you can destroy the chain (say if you are sharing private documents with another legal firm, you can destroy the chain when the case is done, the documents wont be floating in a public chain for perpetuity). the mega chain is a very stupid idea because it forces everything to be hosted by everyone, which very quickly loses feasibility, instead you will likely see an increase in very specific use case chains.", "title": "" }, { "docid": "455952", "text": "Applying for a mortgage is a bit of paperwork, but not too bad of an experience. Rates are pretty tight, if one lender were more that 1/4% lower than another, they'd be inundated with applications. Above a certain credit score, you get the 'best' rate, a search will show you the rates offered in your area. If you are a first time buyer, there are mortgages that might benefit you. If you are a vet (for non-native English readers, a veteran who served in the US armed forces, not a veterinarian, who is an animal doctor) there are mortgages that offer low-to-no down payment with attractive rates. Yes, avoid PMI, it's a crazy penalty on your overall expense of home purchase. If banks qualify you for different amounts, it shouldn't be a huge difference, a few percent variation. But, the standard ratios are pretty liberal even today, and getting the most you'd qualify for is probably too much. Using the standard 28/36% ratios, a bank will qualify you for 4X your income as a loan. e.g you make $50K, they'll lend you $200K. This is a bit too much in my opinion. If you come up short, you are really looking to borrow too much, and should probably wait. If you owe a bit on loans, it should squeeze in between those two ratios, 28/36. But I wouldn't borrow on a credit line to add to the purchase, that's asking for trouble.", "title": "" }, { "docid": "30373", "text": "S & P's site has a methodology link that contains the following which may be of use: Market Capitalization. Unadjusted market capitalization of US$ 4.6 billion or more for the S&P 500, US$ 1.2 billion to US$ 5.1 billion for the S&P MidCap 400, and US$ 350 million to US$ 1.6 billion for the S&P SmallCap 600. The market cap of a potential addition to an index is looked at in the context of its short- and medium-term historical trends, as well as those of its industry. These ranges are reviewed from time to time to assure consistency with market conditions. Liquidity. Adequate liquidity and reasonable price – the ratio of annual dollar value traded to float adjusted market capitalization should be 1.00 or greater, and the company should trade a minimum of 250,000 shares in each of the six months leading up to the evaluation date. Domicile. U.S. companies. For index purposes, a U.S. company has the following characteristics: The final determination of domicile eligibility is made by the U.S. Index Committee.", "title": "" }, { "docid": "542915", "text": "\"Patience has never been my strong suit Unfortunately this is what you need to build up credit. The activities that increase your credit score are paying your bills on time and not using too much of the available credit that you do have. The rest (age of accounts, recent pulls, etc.) are short-term indicators that indicate changes in behavior that will make lenders pause and understand what the reasons behind the events are. Also keep in mind that your credit score shouldn't run your life. It should be a passive indicator of your financial habits - not something that you actively manipulate. Is there anything I can do to raise my score without having to take out a loan with interest? Pay your bills on time, and don't take out more credit than you need. You're already in the \"\"excellent\"\" category, so there's no reason to panic or try to manipulate it. Even if you temporarily dip below, if you need to make a big purchase (house), your loan-to-value and debt/income ratio will be much bigger factors in what interest rate you can get. As far as the BofA card goes, if you don't need it, cancel it. It might cause a temporary dip in your credit, but it will go away quickly, and you're better off not having credit cards that you don't need.\"", "title": "" } ]
PLAIN-1671	mushrooms	[ { "docid": "MED-3302", "text": "In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.", "title": "A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States." }, { "docid": "MED-3308", "text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.", "title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry." }, { "docid": "MED-3294", "text": "In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.", "title": "Emerging and re-emerging swine viruses." }, { "docid": "MED-3704", "text": "The most relevant cause of morbidity and mortality in cystic fibrosis (CF) patients is the lung pathology characterized by chronic infection and inflammation sustained mainly by Pseudomonas aeruginosa (P. aeruginosa). Innovative pharmacological approaches to control the excessive inflammatory process in the lung of CF patients are thought to be beneficial to reduce the extensive airway tissue damage. Medicinal plants from the so-called traditional Asian medicine are attracting a growing interest because of their potential efficacy and safety. Due to the presence of different active compounds in each plant extract, understanding the effect of each component is important to pursue selective and reproducible applications. Extracts from Emblica officinalis (EO) were tested in IB3-1 CF bronchial epithelial cells exposed to the P. aeruginosa laboratory strain PAO1. EO strongly inhibited the PAO1-dependent expression of the neutrophil chemokines IL-8, GRO-alpha, GRO-gamma, of the adhesion molecule ICAM-1 and of the pro-inflammatory cytokine IL-6. Pyrogallol, one of the compounds extracted from EO, inhibited the P. aeruginosa-dependent expression of these pro-inflammatory genes similarly to the whole EO extract, whereas a second compound purified from EO, namely 5-hydroxy-isoquinoline, had no effect. These results identify Pyrogallol as an active compound responsible for the anti-inflammatory effect of EO and suggest to extend the investigation in pre-clinical studies in airway animal models in vivo, to test the efficacy and safety of this molecule in CF chronic lung inflammatory disease.", "title": "Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial..." }, { "docid": "MED-3288", "text": "In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.", "title": "Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue." }, { "docid": "MED-2364", "text": "We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.", "title": "Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides." }, { "docid": "MED-4582", "text": "Objective: Diet may be associated with risk of dementia and Alzheimer's disease (AD). We examined the association between fruit and vegetable consumption in midlife and risk for all types of dementia and AD. Methods: Participants were 3,779 members of the Swedish Twin Registry who completed a diet questionnaire approximately 30 years prior to cognitive screening and full clinical evaluation for dementia as part of the HARMONY study. Among the participants, 355 twins were diagnosed with dementia. Among these, 81 twin pairs were discordant for dementia (50 discordant for AD). Data were analyzed with logistic regression for the entire sample using generalized estimating equations to adjust for relatedness of twins, and with conditional logistic regression for the co-twin control design. Results: In fully-adjusted models, a medium or great proportion of fruits and vegetables in the diet, compared to no or small, was associated with a decreased risk of dementia and AD. This effect was observed among women and those with angina. Similar, but non-significant, odds ratios were found in the co-twin control analyses. Conclusion: Our findings suggest that higher fruit and vegetable consumption may reduce the risk of dementia, especially among women and those with angina pectoris in midlife.", "title": "Midlife Fruit and Vegetable Consumption and Risk of Dementia in Later Life in Swedish Twins" }, { "docid": "MED-2273", "text": "Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.", "title": "Purine-rich foods intake and recurrent gout attacks" }, { "docid": "MED-2363", "text": "We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.", "title": "A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis." }, { "docid": "MED-4309", "text": "Biogenic monoamines such as serotonin, tryptamine, and tyramine function as neurotransmitters and mitogenic factors in animals and are involved in flowering, morphogenesis, and protection from and adaptation to environmental changes in plants. In plants, serotonin and tyramine are conjugated to form phenolic compounds via thioester linkages during the synthesis of hydroxycinnamic acid amides, including p-coumaroylserotonin (CS), feruloylserotonin (FS), p-coumaroyltyramine (CT), and feruloyltyramine (FT). In this study, we determined the amounts of the biogenic monoamines CS, FS, CT, and FT in commonly consumed vegetables using high-performance liquid chromatography. Serotonin, tryptamine, and tyramine were detected in all vegetables tested. The serotonin levels ranged from 1.8 to 294 microg/g of dry weight, the tryptamine levels ranged from 0.8 to 372 microg/g of dry weight, and the tyramine levels ranged from 1.4 to 286 microg/g of dry weight. The highest serotonin and tryptamine contents were found in tomato and cherry tomato (140.3-222 microg/g of dry weight), while paprika and green pepper had higher tyramine contents than the other vegetables (286 and 141.5 microg/g of dry weight, respectively). Overall, the levels of CS, FS, CT, and FT ranged from 0.03 to 13.8 microg/g of dry weight, with green onion possessing the highest levels of CS (0.69 microg/g of dry weight), FT (1.99 microg/g of dry weight), and CT (13.85 microg/g of dry weight).", "title": "HPLC analysis of serotonin, tryptamine, tyramine, and the hydroxycinnamic acid amides of serotonin and tyramine in food vegetables." }, { "docid": "MED-3990", "text": "BACKGROUND: The available evidence on vitamin D and mortality is inconclusive. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. SELECTION CRITERIA: We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. MAIN RESULTS: Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. AUTHORS' CONCLUSIONS: Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.", "title": "Vitamin D supplementation for prevention of mortality in adults." }, { "docid": "MED-3919", "text": "The steroid hormone output of the adrenal gland is crucial in the maintenance of hormonal homeostasis, with hormonal imbalances being associated with numerous clinical conditions which include, amongst others, hypertension, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes. Aspalathus linearis (Rooibos), which has been reported to aid stress-related symptoms linked to metabolic diseases, contains a wide spectrum of bioactive phenolic compounds of which aspalathin is unique. In this study the inhibitory effects of Rooibos and the dihydrochalcones, aspalathin and nothofagin, were investigated on adrenal steroidogenesis. The activities of both cytochrome P450 17α-hydroxylase/17,20 lyase and cytochrome P450 21-hydroxylase were significantly inhibited in COS-1 cells. In order to study the effect of these compounds in H295R cells, a human adrenal carcinoma cell line, a novel UPLC-MS/MS method was developed for the detection and quantification of twenty-one steroid metabolites using a single chromatographic separation. Under both basal and forskolin-stimulated conditions, the total amount of steroids produced in H295R cells significantly decreased in the presence of Rooibos, aspalathin and nothofagin. Under stimulated conditions, Rooibos decreased the total steroid output 4-fold and resulted in a significant reduction of aldosterone and cortisol precursors. Dehydroepiandrosterone-sulfate levels were unchanged, while the levels of androstenedione (A4) and 11β-hydroxyandrostenedione (11βOH-A4) were inhibited 5.5 and 2.3-fold, respectively. Quantification of 11βOH-A4 showed this metabolite to be a major product of steroidogenesis in H295R cells and we confirm, for the first time, that this steroid metabolite is the product of the hydroxylation of A4 by human cytochrome P450 11β-hydroxylase. Taken together our results demonstrate that Rooibos, aspalathin and nothofagin influence steroid hormone biosynthesis and the flux through the mineralocorticoid, glucocorticoid and androgen pathways, thus possibly contributing to the alleviation of negative effects arising from elevated glucocorticoid levels. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The influence of Aspalathus linearis (Rooibos) and dihydrochalcones on adrenal steroidogenesis: quantification of steroid intermediates and end pro..." }, { "docid": "MED-3991", "text": "Few foods contain ergocalciferol or cholecalciferol. Treatment of mushrooms with UV light increases ergocalciferol content and could provide a dietary source of vitamin D. We evaluated the impact of consuming UV-treated white button mushrooms (Agaricus bisporus) on the vitamin D status of healthy adults. Thirty-eight volunteers were randomized to 4 treatments consumed with a standard meal for 6 wk: the control (C) group received untreated mushrooms providing 0.85 μg/d ergocalciferol (n = 10); groups M1 and M2 received UV-treated mushrooms providing 8.8 (n = 10) and 17.1 μg/d (n = 9), respectively; and the supplement (S) group received purified ergocalciferol plus untreated mushrooms, providing a total of 28.2 μg/d (n = 9). Serum total 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyergocalciferol [25(OH)D2] were 83 ± 38 and 2.4 ± 2.0 nmol/L, respectively, at baseline (mean ± SD). At wk 6, 25(OH)D2 had increased and was higher in all treatment groups than in the C group, whereas 25-hydroxycholecalciferol [25(OH)D3] had decreased and was lower in the M2 and S groups than in the C group. Increases in 25(OH)D2 for groups C, M1, M2, and S were 1.2 ± 5.2, 13.8 ± 7.3, 12.7 ± 3.7, and 32.8 ± 3.3 nmol/L and decreases in 25(OH)D3 were -3.9 ± 16.3, -10.4 ± 6.4, -20.6 ± 14.6, and -29.5 ± 15.9 nmol/L, respectively. Concentrations did not change in group C. In summary, ergocalciferol was absorbed and metabolized to 25(OH)D2 but did not affect vitamin D status, because 25(OH)D3 decreased proportionally.", "title": "Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalcifer..." }, { "docid": "MED-3707", "text": "OBJECTIVE: Secretory immunoglobulin A (SIgA) acts as the first line of adaptive humoral immune defense at mucosal surfaces. A lack of SIgA or the inability to produce antigen-specific SIgA can lead to an increased risk of infections. Dietary intake may improve mucosal immunity by accelerating SIgA secretion. This study investigated the effect of dietary intake of Agaricus bisporus white button mushroom (WBM) on salivary IgA (sIgA) secretion in healthy subjects. METHODS: Twenty-four healthy volunteers were randomly assigned to a normal daily diet (control group) or a normal diet with WBM. The subjects in the active group (n = 12, 41.4 ± 11.3 y old) consumed 100 g of blanched WBM daily with their normal diet for 1 wk, whereas those in the control group consumed their normal diet (n = 12, 43.5 ± 12.5 y old) without WBM. Saliva was collected before and after commencement of the study and every week thereafter for 3 wk. Saliva flow rate, sIgA concentration, and osmolality were determined and the sIgA:osmolality ratio and the sIgA secretion rate were calculated. RESULTS: There was no significant difference between pre- and postdietary mushroom intakes for all indices in the control group (P > 0.05). In contrast, the mean sIgA secretion rate increased significantly at weeks 1 and 2 by 53% and 56%, respectively, compared with that at week 0 (P < 0.0005) in the WBM intake group and then returned to a baseline level at week 3. Changes in sIgA secretion rate over the intervention period were greater in the WBM group than in the control group without WBM. In both groups, no significant changes in osmolality and saliva IgG were noted. There was, however, a significant increase in the sIgA:osmolality ratio (P < 0.0012), confirming the postdietary WBM-induced sIgA increase. CONCLUSION: The dietary intake of A. bisporus WBM significantly accelerates sIgA secretion, thereby indicating its potential health benefits for improving mucosal immunity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.", "title": "Dietary intake of Agaricus bisporus white button mushroom accelerates salivary immunoglobulin A secretion in healthy volunteers." }, { "docid": "MED-3703", "text": "OBJECTIVE: To provide an overview of what is currently known about the relationship between allergies and cancer. DATA SOURCES: Publications were selected from a systematic review of the English-language literature from established databases (eg, MEDLINE, EBSCO) and the references of materials identified through these databases. STUDY SELECTION: Publications assessing the association between asthma, hay fever, or other allergy-related diseases and cancer were included in this review. RESULTS: Individuals with any type of allergy have a decreased risk for cancer (compared with the general population), including glioma, colorectal cancer, cancer of the larynx, non-Hodgkin lymphoma, cancer of the esophagus, oral cancer, pancreatic cancer, stomach cancer, and uterine body cancer. However, an increased risk for bladder cancer, lymphoma, myeloma, and prostate cancer exists among those with allergies. Studies that involve breast cancer, leukemia, lung cancer, melanoma, and thyroid cancer have shown no association or conflicting results related to allergies. More research is needed before conclusions can be made about the relation between allergies and Kaposi sarcoma, liver cancer, and cancer of the ovaries. CONCLUSIONS: The association between allergies and cancer is site specific. Further research is needed to verify these results and to determine why such associations exist.", "title": "The association between allergies and cancer: what is currently known?" }, { "docid": "MED-5048", "text": "Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.", "title": "Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells." }, { "docid": "MED-3318", "text": "Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.", "title": "Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium" }, { "docid": "MED-3317", "text": "Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.", "title": "Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain." }, { "docid": "MED-1298", "text": "Obesity-induced insulin resistance has been suggested to be a systemic inflammatory condition with activation of the innate immune system. Animal studies indicate that certain dietary fibers such as (1,3)(1,6)-beta-D-glycans (BDG) have potent effects on immune activity such as increasing the antiinflammatory cytokine interleukin-10 (IL-10) and reducing the secretion of inflammatory factors. Therefore, we hypothesized that BDG consumption improves inflammatory markers and insulin sensitivity in overweight and obese subjects with moderately increased levels of C-reactive protein, indicating subclinical inflammation. We screened 180 overweight and obese subjects for moderately increased C-reactive protein levels on 2 or more occasions, in the absence of any signs of acute infection. Twelve of the subjects met all inclusion criteria and were investigated in a randomized, double-blind, placebo-controlled, crossover design for 2 x 4 weeks (washout > or =4 weeks). Subjects ingested capsules containing 3 x 0.5 g of highly purified BDG or 3 x 0.5 g of placebo (waxy maize starch) daily. Maintenance of the normal diet of the participants and the correct intake of the capsules were monitored, using 6 x 3-day food recording and counting of the provided capsules. Predefined outcome measures were BDG-induced changes in pro and antiinflammatory markers in circulating blood and gene expression in adipose tissue and peripheral insulin sensitivity expressed as M value. The BDG consumption for 4 weeks significantly increased both circulating levels and adipose tissue messenger RNA (mRNA) expression of the antiinflammatory cytokine IL-10 in overweight and obese humans. Insulin sensitivity as well as circulating levels and mRNA expression of proinflammatory cytokines were unaffected by BDG treatment. Increased IL-10 after BDG consumption might be a contributing factor to the known beneficial effects of dietary fiber intake.", "title": "Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-beta-glycan consumption in overweight humans." }, { "docid": "MED-4096", "text": "A variety of statistics are used to quantify the burden (occurrence and outcome) of cancer generally and of breast cancer specifically. When undertaking any cancer control program, understanding these statistics, their source, and their quality is important for assessing the current situation, allocating resources to different control strategies, and evaluating progress. Two core statistics are the cancer incidence rate and the cancer mortality rate, which provide estimates of the average risk of acquiring and of dying from the disease, respectively. About 16% of the world's population is covered by registration systems that produce cancer incidence statistics, while mortality data are available for about 29%. Breast cancer incidence and mortality vary considerably by world region. In general, the incidence is high (greater than 80 per 100,000) in developed regions of the world and low (less than 30 per 100,000), though increasing, in developing regions; the range of mortality rates is much less (approximately 6-23 per 100,000) because of the more favorable survival of breast cancer in (high-incidence) developed regions. The incidence of breast cancer is increasing almost everywhere. This unfavorable trend is due in part to increases in risk factors (decreased childbearing and breast-feeding, increased exogenous hormone exposure, and detrimental dietary and lifestyle changes, including obesity and less physical activity). On the other hand, mortality is now decreasing in many high-risk countries due to a combination of intensified early detection efforts and the introduction of mammographic screening, resulting in the diagnosis of more small, early stage tumors, and advances in treatment.", "title": "Use of statistics to assess the global burden of breast cancer." }, { "docid": "MED-2354", "text": "A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.", "title": "A unique natural human IgG antibody with anti-alpha-galactosyl specificity" }, { "docid": "MED-2353", "text": "Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.", "title": "Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits" }, { "docid": "MED-1292", "text": "There has been enormous interest in the biologic activity of mushrooms and innumerable claims have been made that mushrooms have beneficial effects on immune function with subsequent implications for inhibition of tumor growth. The majority of these observations are anecdotal and often lack standardization. However, there remains considerable data on both in vitro and in vivo effects that reflect on the potential of mushroom compounds to influence human immunity. A number of these effects are beneficial but, unfortunately, many responses are still characterized based on phenomenology and there is more speculation than substance. With respect to tumor biology, although many neoplastic lesions are immunogenic, tumor antigens frequently are self antigens and induce tolerance and many patients with cancer exhibit suppressed immune responses, including defective antigen presentation. Therefore, if and when mushroom extracts are effective, they more likely function as a result of improved antigen presentation by dendritic cells than by a direct cytopathic effect. In this review we attempt to place these data in perspective, with a particular focus on dendritic cell populations and the ability of mushroom extracts to modulate immunity. There is, at present, no scientific basis for the use of either mushrooms or mushroom extracts in the treatment of human patients but there is significant potential for rigorous research to understand the potential of mushrooms in human disease and thence to focus on appropriate clinical trials to demonstrate effectiveness and/ or potential toxicity.", "title": "The immunobiology of mushrooms." }, { "docid": "MED-4581", "text": "We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.", "title": "Fruit and vegetable consumption and cognitive decline in aging women." }, { "docid": "MED-3710", "text": "A two-step method was developed to quantitatively assess the infection rate of the entomophthoraceous fungus, Zoophthora anhuiensis (Li) Humber, on the green peach aphid, Myzus persicae (Sulzer). Firstly, a standard time-dose-mortality relationship, established by modeling data from bioassay 1 at varying conidial dosages (0.4 - 10.4 conidia/mm2) of Z. anhuiensis F97028, was used to yield an estimate of expected mortality probability at a given dosage. Secondly, bioassay 2 was conducted by simultaneously exposing six < or = 4-day-old nymphal colonies to a shower of Z. anhuiensis conidia at each of four dosages (resulting from exposures of 0.3 - 8.0 min). Subsequently, the colonies were separately immersed in a 0.1% chlorothalonil solution for 0.5 min to disinfect all surviving conidia on the host integument from 1 - 12 h after exposure under temperature treatments of 15 and 20 degrees C, respectively. The infection rate during a specific period from the end of the exposure to the immersion was then estimated as the ratio of the observed mortality over the expected mortality probability at a particular dosage. The results showed that the infection of M. persicae from Z. anhuiensis was highly rapid with little difference between aphid colonies maintained at 15 and 20 degrees C before being immersed in the fungicidal solution after exposure. The first 6-hour period after exposure was most crucial to successful infection of the fungus with the infection rate greatly depending on conidial dosages. It took < or = 1 h to infect > 50% of the aphids at a dosage of > 1.5 conida/mm2 and > 90% at > 50 conidia/mm2.", "title": "Quantitative assessment of the infection rate of the entomophthoraceous fungus, Zoophthora anhuiensis against the green peach aphid Myzus persicae." }, { "docid": "MED-3989", "text": "Vitamin D(2) (ergocalciferol) and sterols were analyzed in mushrooms sampled nationwide in the United States to update the USDA Nutrient Database for Standard Reference. Vitamin D(2) was assayed using HPLC with [(3)H]-vitamin D(3) internal standard and sterols by GC-FID mass spectrometric (MS) confirmation. Vitamin D(2) was low (0.1-0.3 μg/100 g) in Agaricus bisporus (white button, crimini, portabella) and enoki, moderate in shiitake and oyster (0.4-0.7 μg/100 g), and high in morel, chanterelle, maitake (5.2-28.1 μg/100 g) and UV-treated portabella (3.4-20.9 μg/100 g), with significant variability among composites for some types. Ergosterol (mg/100 g) was highest in maitake and shiitake (79.2, 84.9) and lowest in morel and enoki (26.3, 35.5); the range was <10 mg/100 g among white button composites but 12-50 mg/100 g among samples of other types. All mushrooms contained ergosta-5,7-dienol (22,23-dihydroergosterol) (3.53-18.0 mg/100 g) and (except morel) ergosta-7-enol. Only morel contained brassicasterol (28.6 mg/100 g) and campesterol (1.23-4.54 mg/100 g) and no ergosta-7,22-dienol. MS was critical in distinguishing campesterol from ergosta-7,22-dienol.", "title": "Vitamin D and sterol composition of 10 types of mushrooms from retail suppliers in the United States." }, { "docid": "MED-2360", "text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.", "title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness." }, { "docid": "MED-3706", "text": "Autoimmune diseases are complex diseases resulting of the interaction between both genetics and environmental factors over time. Different phases in the development of autoimmune diseases are characterized by the detection of serum autoantibodies several months or years before the onset of clinical manifestations and subsequent diagnosis. In addition to serum antibodies, genetic susceptibility factors may predict the future development of the disease. Currently, prediction in type 1 diabetes is the most accurate, with the analysis of genetic susceptibility factors in first-degree relatives of patients and several autoantibody tests. In the future, multiple antibodies test, in combination with the analysis of genetics, epigenetics and immunological anomalies in fine models may allow the precise prediction in autoimmune diseases. Prevention measures might thus be introduced as an attempt to avoid or delay the disease. Copyright Â© 2011 Elsevier B.V. All rights reserved.", "title": "Are autoimmune diseases predictable?" }, { "docid": "MED-3986", "text": "BACKGROUND/OBJECTIVES: Mushrooms contain very little or any vitamin D(2) but are abundant in ergosterol, which can be converted into vitamin D(2) by ultraviolet (UV) irradiation. Our objective was to investigate the bioavailability of vitamin D(2) from vitamin D(2)-enhanced mushrooms by UV-B in humans, and comparing it with a vitamin D(2) supplement. SUBJECTS/METHODS: Fresh mushrooms were irradiated with an UV-B dose of 1.5 J/cm(2), increasing vitamin D(2) content from <1 to 491 μg/100 g and made to an experimental soup. In this 5-week, single-blinded, randomized, placebo-controlled trial, 26 young subjects with serum 25-hydroxyvitamin D (25OHD) ≤ 50 nmol/l were randomly assigned into three groups ((a) mushroom, (b) supplement and (c) placebo). They received during winter (a) 28,000 IU (700 μg) vitamin D(2) via the experimental soup, or (b) 28,000 IU vitamin D(2) via a supplement or (c) placebo, respectively. RESULTS: After 2 weeks, serum 25OHD was significantly higher in the mushroom than in the placebo group (P=0.001). The serum 25OHD concentrations in the mushroom and supplement groups rose significantly and similarly over the study period by 3.9 nmol/l (95% confidence interval (95% CI): 2.9, 4.8) and by 4.7 nmol/l per week (95% CI: 3.8, 5.7), respectively. CONCLUSIONS: We are the first to demonstrate in humans that the bioavailability of vitamin D(2) from vitamin D(2)-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D(2) supplement. This trial was registered at http://germanctr.de as DRKS00000195.", "title": "Bioavailability of vitamin D₂ from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D: a randomized controll..." }, { "docid": "MED-4881", "text": "The effects of microbial transglutaminase (MTGase) at different levels (0 to 0.8 units/g sample) on the properties of gels from lizardfish (Saurida undosquamis) mince set at 25 degrees C for 2 h or 40 degrees C for 30 min prior to heating at 90 degrees C for 20 min were studied. Breaking force and deformation of gels increased with increasing MTGase amount added (P<0.05). At the same MTGase level used, gels with the prior setting at 40 degrees C for 30 min showed a higher breaking force compared with those subjected to prior setting at 25 degrees C for 2 h (P<0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoretic study revealed that myosin heavy chain (MHC) underwent polymerization to a higher extent in the presence of MTGase. Regardless of setting condition, microstructure of gel added with MTGase was finer with a smaller void compared with that of gel without MTGase. Therefore, setting temperature affected the property of gels added with MTGase. Gel properties of mince obtained from lizardfish stored in ice for different times (0 to 10 d) with and without MTGase at a level 0.6 units/g were determined. Irrespective of MTGase addition, breaking force and deformation of all gels decreased as the storage time of lizardfish increased (P<0.05). The addition of MTGase was able to increase both breaking force and deformation of the resulting gel produced from lizardfish kept in ice for all storage times used. Therefore, both freshness and MTGase addition had the direct impact on gel properties of lizardfish mince.", "title": "Improvement of gelling properties of lizardfish mince as influenced by microbial transglutaminase and fish freshness." }, { "docid": "MED-4882", "text": "OBJECTIVE: To determine whether chicken-based formula can replace soy-based formula in infants with cow milk allergy. SUBJECTS AND METHODS: Thirty-eight infants with cow's milk allergy, aged between 2-24 months of age were randomized to receive either chicken-based formula or soy-based formula for 14 days. RESULTS: In the group of soy-based formula, 12 out of 18 infants had evidence of intolerance and could not continue with the formula. However, only 4 out of 20 infants in the chicken-based formula group had evidence of clinical intolerance. All other 16 infants were fed the chicken-based formula with success. The number of infants who were intolerant to chicken formula was significantly lower than the number of those fed soy-based formula (p = 0.009). CONCLUSION: Chicken-based formula can be used more effectively than soy-based formula in infants with cow milk allergy.", "title": "Comparisons of a chicken-based formula with soy-based formula in infants with cow milk allergy." }, { "docid": "MED-2272", "text": "To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.", "title": "Consumption of cherries lowers plasma urate in healthy women." }, { "docid": "MED-5047", "text": "Our objective was to examine whether habitual green tea consumption is associated with blood glucose levels and other biomarkers of glucose metabolism. We conducted a cross-sectional study of 35 male volunteers, 23–63 years old and residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we conducted a questionnaire survey on health, lifestyle, and nutrition, as well as frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men who consumed a 3% concentration of green tea showed lower mean values of fasting blood glucose and fructosamine than those who consumed a 1% concentration. Fasting blood glucose levels were found to be significantly associated with green tea concentration (β = −0.14, p = 0.03). However, green tea consumption frequency showed no significant differences in mean levels of blood glucose, fructosamine and hemoglobin A1c. In conclusion, our findings suggest that the consumption of green tea at a high concentration has the potential to reduce blood glucose levels.", "title": "The Association between Concentrations of Green Tea and Blood Glucose Levels" }, { "docid": "MED-3700", "text": "Background An increased risk of breast cancer is associated with alcohol consumption; however, it is controversial whether red wine increases this risk. Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine. We tested whether red wine is a nutritional AI in premenopausal women. Methods In a cross-over design, 36 women (mean age [SD], 36 [8] years) were assigned to 8 ounces (237 mL) of red wine daily then white wine for 1 month each, or the reverse. Blood was collected twice during the menstrual cycle for measurement of estradiol (E2), estrone (E1), androstenedione (A), total and free testosterone (T), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH). Results Red wine demonstrated higher free T vs. white wine (mean difference 0.64 pg/mL [0.2 SE], p=0.009) and lower SHBG (mean difference −5.0 nmol/L [1.9 SE], p=0.007). E2 levels were lower in red vs. white wine but not statistically significant. LH was significantly higher in red vs. white wine (mean difference 2.3 mIU/mL [1.3 SE], p=0.027); however, FSH was not. Conclusion Red wine is associated with significantly higher free T and lower SHBG levels, as well as a significant higher LH level vs. white wine in healthy premenopausal women. These data suggest that red wine is a nutritional AI and may explain the observation that red wine does not appear to increase breast cancer risk.", "title": "Red Versus White Wine as a Nutritional Aromatase Inhibitor in Premenopausal Women: A Pilot Study" }, { "docid": "MED-3988", "text": "Context: Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status. Objective: Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3. Subjects and Design: This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18–84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter. Results: Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean ± sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9 ± 10.5 ng/ml; 11 wk 26.8 ± 9.6 ng/ml), vitamin D3 (baseline 19.6 ± 11.1 ng/ml; 11 wk 28.9 ± 11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2 ± 10.4 ng/ml; 11 wk 28.4 ± 7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml. Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.", "title": "Vitamin D2 Is as Effective as Vitamin D3 in Maintaining Circulating Concentrations of 25-Hydroxyvitamin D" }, { "docid": "MED-4312", "text": "Eosinophilia–myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. An epidemic of EMS in 1989 was linked to L-tryptophan consumption originating from a single source. Following the Food and Drug Administration (FDA) ban on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been published since the FDA ban was lifted in 2005. We report the clinical, histopathological and immunogenetic features of a new case of L-tryptophan-associated EMS along with evidence of activated transforming growth factor-ß and interleukin-4 signaling in the lesional skin.", "title": "Post-epidemic eosinophilia myalgia syndrome associated with L-Tryptophan" }, { "docid": "MED-3920", "text": "Green tea is reported to have wide ranging beneficial health outcomes across epidemiological studies, which have been attributed to its flavonoid content. We investigated whether the flavonoid epigallocatechin gallate (EGCG) modulates brain activity and self-reported mood in a double-blind, placebo controlled crossover study. Participants completed baseline assessments of cognitive and cardiovascular functioning, mood and a resting state electroencephalogram (EEG) before and then 120 min following administration of 300 mg EGCG or matched placebo. EGCG administration was associated with a significant overall increase in alpha, beta and theta activity, also reflected in overall EEG activity, more dominant in midline frontal and central regions, specifically in the frontal gyrus and medial frontal gyrus. In comparison to placebo the EGCG treatment also increased self-rated calmness and reduced self rated stress. This pattern of results suggests that participants in the EGCG condition may have been in a more relaxed and attentive state after consuming EGCG. This is in keeping with the widespread consumption of green tea for its purported relaxing/refreshing properties. The modulation of brain function due to EGCG is deserving of further controlled human studies. Copyright Â© 2011 Elsevier Ltd. All rights reserved.", "title": "Acute neurocognitive effects of epigallocatechin gallate (EGCG)." }, { "docid": "MED-2352", "text": "BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.", "title": "Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose." }, { "docid": "MED-2356", "text": "Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.", "title": "The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose" }, { "docid": "MED-3307", "text": "OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.", "title": "Mortality in workers employed in pig abattoirs and processing plants." }, { "docid": "MED-2365", "text": "Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).", "title": "An association between tick bite reactions and red meat allergy in humans." }, { "docid": "MED-1293", "text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.", "title": "Immunity: plants as effective mediators." }, { "docid": "MED-4651", "text": "BACKGROUND: Several publications reported breast cancer incidence rates continued to decrease among white women, following the decline of about 7% from 2002 to 2003. However, none of these reports exclusively examined the trend after 2003. In this paper, we examined breast cancer incidence rates among non-Hispanic (NH) white women from 2003 to 2007 to determine whether the decrease in breast cancer incidence rates indeed persisted through 2007. In addition, we present breast cancer incidence trends for NH black and Hispanic women and postmenopausal hormone use for all three racial/ethnic groups. METHODS: Breast cancer incidence rates were calculated by race/ethnicity, age and ER status using data from the Surveillance, Epidemiology, and End Results (SEER) 12 registries for 2000 to 2007. Prevalence of postmenopausal hormone use was calculated using National Health Interview Survey data from 2000, 2005, and 2008. RESULTS: From 2003 to 2007, overall breast cancer incidence rates did not change significantly among NH white women in any age group. However, rates increased (2.7% per year) for ER+ breast cancers in ages 40 to 49, and decreased for ER- breast cancers in ages 40 to 49 and 60 to 69. Similarly, overall breast cancer incidence rates did not change significantly for black and Hispanic women. Hormone use continued to decrease from 2005 to 2008 in all groups, although the decreases were smaller compared to those from 2000 to 2005. CONCLUSIONS: The sharp decline in breast cancer incidence rates that occurred from 2002 to 2003 among NH white women did not continue through 2007. IMPACT: Further studies are needed to better understand the recent breast cancer trends. ©2011 AACR.", "title": "Breast cancer incidence rates in U.S. women are no longer declining." }, { "docid": "MED-1294", "text": "Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.", "title": "Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan" }, { "docid": "MED-3985", "text": "Deficiency of vitamin D is usually caused by dietary deficiency and/or lack of exposure to sunlight in dark skinned individuals living at northern latitudes. Simple vitamin D deficiency is commonly treated by prescribing a vitamin D containing calcium supplement. This report presents a patient who rejected this approach and instead, after researching alternative treatment options independently, opted to self-treat by consuming UVB-irradiated mushrooms. The beneficial effect of this on the patient's plasma biochemical markers is shown. Further research into the beneficial effect of consuming UVB-irradiated mushrooms is required.", "title": "Vitamin D deficiency treated by consuming UVB-irradiated mushrooms" }, { "docid": "MED-3702", "text": "BACKGROUND: Increased prevalence of allergic diseases in western societies has been described as an epidemic. The precise turning point for the epidemic and the antigens responsible for it remain obscure. OBJECTIVE: To evaluate how the prevalence of atopic disease has changed in terms of detectable sensitization to aeroallergens and dietary allergens in a cross-sectional comparison of subjects from birth cohorts more than 60 years apart. METHODS: We studied four groups of 100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in 1990, 1963-66, 1943-46 and in 1923-26, respectively. Serum total and specific IgE concentrations against aeroallergens and dietary allergens were determined. A questionnaire elicited information on symptoms, allergic diseases and medication. RESULTS: The proportion of subjects with detectable IgE antibodies against aeroallergens increased consistently from the oldest to the youngest birth cohorts; chi2 trend=56.809, P<0.0001. Similar progression was not seen in sensitization to dietary allergens. The proportion of those with diagnosed asthma differed significantly (chi2=13.45, P=0.004) across the birth cohorts. The lowest prevalence of asthma and sensitization to dietary allergens was detected in those born in 1943-46, i.e. during or immediately after World War II. CONCLUSION: Prevalence of sensitization to airborne allergens, unlike that to dietary allergens, has increased over a long period of time. Our results support the concept of the immune function being programmed by external factors early in life. They also call for caution when interpretations of the pace and possible causes of the allergy epidemic are made on the basis of short-term studies.", "title": "The allergy epidemic extends beyond the past few decades." }, { "docid": "MED-3464", "text": "The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.", "title": "Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women." }, { "docid": "MED-2362", "text": "The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G..." }, { "docid": "MED-1291", "text": "There is significant interest in the use of mushrooms and/or mushroom extracts as dietary supplements based on theories that they enhance immune function and promote health. To some extent, select mushrooms have been shown to have stimulatory action on immune responsiveness, particularly when studied in vitro. However, despite their widespread use for potential health benefits, there is a surprising paucity of epidemiologic and experimental studies that address the biologic activities of mushrooms after oral administration to animals or humans. There have been a number of studies that have addressed the ability of mushrooms to modulate mononuclear cell activation and the phenotypic expression of cytokines and their cognate receptors. There have also been a number of attempts to determine antitumor activities of mushrooms. Such studies are important because many of the components of mushrooms do potentially have significant biologic activity. All data, however, should be tempered by the possibility that there are toxic levels of metals, including arsenic, lead, cadmium, and mercury as well as the presence of radioactive contamination with 137Cs. In this review, we will present the comparative biology with respect to both immunological and antitumor activities of mushroom extracts and also highlight the need for further evidence-based research.", "title": "Mushrooms, tumors, and immunity: an update." }, { "docid": "MED-3923", "text": "OBJECTIVE: Inadvertent exposure to the ubiquitous weed, Urtica dioica, called \"stinging nettles\" produces an immediate stinging and burning sensation on the skin. This investigation evaluates the structural effect that stinging nettle spicules may have on the clinical manifestation of these symptoms. This hypothesis was investigated by exposing murine skin to stinging nettles and then evaluating the skin using electron microscopy. It was hypothesized that the mechanism of action of stinging nettles is both biochemical and mechanical, which may have clinical significance regarding treatment for acute exposure. METHODS: Fresh post-mortem dermis samples from the carcasses of genetically modified hairless mice were brushed under the stem and leaf of a stinging nettle plant, mimicking the clinical method of exposure a patient might experience. Another set of mouse skin samples was obtained but not exposed to the nettles. Both sets of skin samples were imaged with scanning electron microscopy. RESULTS: The skin samples that were not exposed to nettle leaves were uniform, with occasional striated hairs on the skin surface and no nettle spicules. The skin samples exposed to nettle leaves showed many smooth nettle spicules piercing the skin surface. A few spicules retained their bases, which appear empty of any liquid contents. CONCLUSIONS: The mechanism of action of stinging nettles dermatitis appears to be both biochemical and mechanical. Impalement of spicules into the skin likely accounts for the mechanical irritation in addition to the known adverse chemical effects of stinging nettles. Further investigation of treatment modalities is warranted. Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.", "title": "Mechanism of action of stinging nettles." }, { "docid": "MED-5171", "text": "The objective of this study was to determine the prevalence of enterohemorrhagic Escherichia coli (EHEC), E. coli O157, Salmonella, and Listeria monocytogenes in retail food samples from Seattle, Wash. A total of 2,050 samples of ground beef (1,750 samples), mushrooms (100 samples), and sprouts (200 samples) were collected over a 12-month period and analyzed for the presence of these pathogens. PCR assays, followed by culture confirmation were used to determine the presence or absence of each organism. Of the 1,750 ground beef samples analyzed, 61 (3.5%) were positive for EHEC, and 20 (1.1%) of these were positive for E. coli O157. Salmonella was present in 67 (3.8%) of the 1,750 ground beef samples. Of 512 ground beef samples analyzed, 18 (3.5%) were positive for L. monocytogenes. EHEC was found in 12 (6.0%) of the 200 sprout samples, and 3 (1.5%) of these yielded E. coli O157. Of the 200 total sprout samples, 14 (7.0%) were positive for Salmonella and none were positive for L. monocytogenes. Among the 100 mushroom samples, 4 (4.0%) were positive for EHEC but none of these 4 samples were positive for E. coli O157. Salmonella was detected in 5 (5.0%) of the mushroom samples, and L. monocytogenes was found in 1 (1.0%) of the samples.", "title": "Incidence of enterohemorrhagic Escherichia coli, Escherichia coli O157, Salmonella, and Listeria monocytogenes in retail fresh ground beef, sprouts..." }, { "docid": "MED-1299", "text": "OBJECTIVE: Several studies have shown a baker's yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. This study evaluated the effect of a specific beta-glucan supplement (Wellmune) on upper respiratory tract symptoms and psychological well-being in women with moderate levels of psychological stress. METHODS: Healthy women (38 ± 12 years old) prescreened for moderate levels of psychological stress, self-administered a placebo (n = 38) or 250 mg of Wellmune (n = 39) daily for 12 weeks. We used the Profile of Mood States (POMS) psychological survey to assess changes in mental/physical energy levels (vigor) and overall well-being (global mood state). A quantitative health perception log was used to track upper respiratory symptoms. RESULTS: Subjects in the Wellmune group reported fewer upper respiratory symptoms compared to placebo (10% vs 29%), better overall well-being (global mood state: 99 ± 19 vs 108 ± 23, p < 0.05), and superior mental/physical energy levels (vigor: 19.9 ± 4.7 vs 15.8 ± 6.3, p < 0.05). CONCLUSIONS: These data show that daily dietary supplementation with Wellmune reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors.", "title": "Baker's yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women." }, { "docid": "MED-4884", "text": "In this study, magnetic resonance imaging (MRI) was applied to study the structural aspects of the tomato fruit. The main study was performed on tomatoes (cv. Tradiro) using a 0.2-T electromagnet scanner. Spin-echo images were acquired to visualize the tomato macrostructure. The air bubble content in tissues was evaluated by exploiting susceptibility effects using multiple gradient echo images. The microstructure was further studied by measuring spin-spin (T(2)) and spin-lattice (T(1)) relaxation time distributions. Nuclear magnetic resonance relaxometry, macro vision imaging and chemical analysis were used as complementary and independent experimental methods in order to emphasize the MRI results. MRI images showed that the air bubble content varied between tissues. The presence of gas was attested by macro vision images. Quantitative imaging showed that T(2) and T(1) maps obtained by MRI reflected the structural differences between tomato tissues and made it possible to distinguish between them. The results indicated that cell size and chemical composition contribute to the relaxation mechanism.", "title": "An investigation of the structural aspects of the tomato fruit by means of quantitative nuclear magnetic resonance imaging." }, { "docid": "MED-2278", "text": "OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.", "title": "Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats." }, { "docid": "MED-4098", "text": "To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.", "title": "Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women." }, { "docid": "MED-3922", "text": "The aqueous extracts of Hibiscus sabdariffa have been commonly used in folk medicine. Nevertheless, the compounds or metabolites responsible for its healthy effects have not yet been identified. The major metabolites present in rat plasma after acute ingestion of a polyphenol-enriched Hibiscus sabdariffa extract were characterized and quantified in order to study their bioavailability. The antioxidant status of the plasma samples was also measured through several complementary antioxidant techniques. High-performance liquid chromatography coupled to time-of-flight mass spectrometry (HPLC-ESI-TOF-MS) was used for the bioavailability study. The antioxidant status was measured by ferric reducing ability of plasma method, thiobarbituric acid reactive substances assay, and superoxide dismutase activity assay. Seventeen polyphenols and metabolites have been detected and quantified. Eleven of these compounds were metabolites. Although phenolic acids were found in plasma without any modification in their structures, most flavonols were found as quercetin or kaempferol glucuronide conjugates. Flavonol glucuronide conjugates, which show longer half-life elimination values, are proposed to contribute to the observed lipid peroxidation inhibitory activity in the cellular membranes. By contrast, phenolic acids appear to exert their antioxidant activity through ferric ion reduction and superoxide scavenging at shorter times. We propose that flavonol-conjugated forms (quercetin and kaempferol) may be the compounds responsible for the observed antioxidant effects and contribute to the healthy effects of H. sabdariffa polyphenolic extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Bioavailability study of a polyphenol-enriched extract from Hibiscus sabdariffa in rats and associated antioxidant status." }, { "docid": "MED-3314", "text": "OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.", "title": "Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)." }, { "docid": "MED-4720", "text": "Tritiated naloxone, a powerful opiate antagonist, specifically binds to an opiate receptor of mammalian brain and guinea pig intestine. Competition for the opiate receptor by various opiates and their antagonists closely parallels their pharmacological potency. The opiate receptor is confined to nervous tissue.", "title": "Opiate receptor: demonstration in nervous tissue." }, { "docid": "MED-3313", "text": "INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.", "title": "Occupational toxicology of asbestos-related malignancies." }, { "docid": "MED-3987", "text": "Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.", "title": "Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis" }, { "docid": "MED-2366", "text": "Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.", "title": "A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis." }, { "docid": "MED-3292", "text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.", "title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G" }, { "docid": "MED-3701", "text": "Estrogen synthesized in situ plays a more important role in breast cancer cell proliferation than does circulating estrogen. Aromatase is the enzyme that converts androgen to estrogen and is expressed at a higher level in breast cancer tissue than in surrounding noncancer tissue. A promising route of chemoprevention against breast cancer may be through the suppression of in situ estrogen formation using aromatase inhibitors. A diet high in fruits and vegetables may reduce the incidence of breast cancer, because they contain phytochemicals that can act as aromatase inhibitors. In our previous studies, we found that grapes and wine contain potent phytochemicals that can inhibit aromatase. We show that red wine was more effective than white wine in suppressing aromatase activity. Interestingly, our results from white wine studies suggest a weak inductive effect of alcohol on aromatase activity. On the other hand, the potent effect of anti-aromatase chemicals in red wine overcomes the weak inductive effect of alcohol in wine. Several purification procedures were performed on whole red wine to separate active aromatase inhibitors from non-active compounds. These techniques included liquid-liquid extraction, silica gel chromatography, various solid phase extraction (SPE) columns, and high performance liquid chromatography. An active Pinot Noir red wine SPE C18 column fraction (20% acetonitrile:water) was more effective than complete Pinot Noir wine in suppressing aromatase assay. This red wine extract was further analyzed in a transgenic mouse model in which aromatase was over-expressed in mammary tissue. Our gavaged red wine extract completely abrogated aromatase-induced hyperplasia and other neoplastic changes in mammary tissue. These results suggest that red wine or red wine extract may be a chemopreventive diet supplement for postmenopausal women who have a high risk of breast cancer. Further research is underway to purify and characterize the active compounds in red wine that are responsible for the inhibition of aromatase.", "title": "Anti-aromatase chemicals in red wine." }, { "docid": "MED-3310", "text": "We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.", "title": "A new type of Hypersensitivity Pneumonitis: salami brusher's disease." }, { "docid": "MED-3712", "text": "Herein, it was reported and compared the chemical composition and nutritional value of the most consumed species as fresh cultivated mushrooms: Agaricus bisporus (white and brown mushrooms), Pleurotus ostreatus (oyster mushroom), Pleurotus eryngii (King oyster mushroom), Lentinula edodes (Shiitake) and Flammulina velutipes (Golden needle mushroom). Shiitake revealed the highest levels of macronutrients, unless proteins, as also the highest sugars, tocopherols and PUFA levels, and the lowest SFA content. White and brown mushrooms showed similar macronutrients composition, as also similar values of total sugars, MUFA, PUFA and total tocopherols. Oyster and king oyster mushrooms gave the highest MUFA contents with similar contents in PUFA, MUFA and SFA in both samples. They also revealed similar moisture, ash, carbohydrates and energy values. This study contributes to the elaboration of nutritional databases of the most consumed fungi species worldwide, allowing comparison between them. Moreover it was reported that cultivated and the wild samples of the same species have different chemical composition, including sugars, fatty acids and tocopherols profiles. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Chemical composition and nutritional value of the most widely appreciated cultivated mushrooms: an inter-species comparative study." }, { "docid": "MED-3921", "text": "BACKGROUND: To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). RESULTS: HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). CONCLUSION: The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.", "title": "Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects." }, { "docid": "MED-3698", "text": "Purpose Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. Patients and Methods A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. Results In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers. Conclusion A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.", "title": "Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity" }, { "docid": "MED-2359", "text": "INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Anti-Gal titers in healthy adults and inflammatory bowel disease patients." }, { "docid": "MED-4583", "text": "Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.", "title": "Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study." }, { "docid": "MED-3709", "text": "The gut immune system has the challenge of responding to pathogens while remaining relatively unresponsive to food antigens and the commensal microflora. In the developed world, this ability appears to be breaking down, with chronic inflammatory diseases of the gut commonplace in the apparent absence of overt infections. In both mouse and man, mutations in genes that control innate immune recognition, adaptive immunity, and epithelial permeability are all associated with gut inflammation. This suggests that perturbing homeostasis between gut antigens and host immunity represents a critical determinant in the development of gut inflammation and allergy.", "title": "Immunity, inflammation, and allergy in the gut." }, { "docid": "MED-1300", "text": "Purpose The effect of brewers’ yeast (1,3)-(1,6)-beta-d-glucan consumption on the number of common cold episodes in healthy subject was investigated. Methods In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-d-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode. Results In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25 % as compared to placebo (p = 0.041). The mean symptom score was 15 % lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012). Conclusion The present study demonstrated that yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.", "title": "Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects" }, { "docid": "MED-3713", "text": "BACKGROUND: Th17 is a subset of T-helper lymphocytes that produce proinflammatory cytokines, mainly IL-17. Serum IL-17 is increased in allergic patients and relates to clinical severity. Recently, it has been reported that CD161 is a highly upregulated gene in Th17 clones and all IL-17-producing cells are contained in CD161(+) T cells. This study aimed at comparing the frequency of peripheral CD161(+) T cells in patients with allergic rhinitis (AR) and in healthy controls and at relating CD161 expression with symptom severity. METHODS: Forty-four patients with AR and 29 healthy non-allergic subjects were evaluated. CD161 expression was evaluated on CD3(+), CD4(+) and CD8(+) cells by double immunofluorescence staining and fluorescence activated cell sorter analysis. Symptom severity was assessed by the Visual Analogue Scale. RESULTS: Allergic patients showed a significantly higher frequency of CD3(+)CD161(+), CD4(+)CD161(+) and CD8(+)CD161(+) cells than healthy non-allergic subjects (p < 0.0001). Moreover, the expression of CD161 cells was significantly related to clinical severity. CONCLUSIONS: This study provides evidence that a higher frequency of CD161(+) T cells is present in the peripheral blood of AR patients. Copyright © 2012 S. Karger AG, Basel.", "title": "Higher frequencies of CD161+ circulating T lymphocytes in allergic rhinitis patients compared to healthy donors." }, { "docid": "MED-2355", "text": "Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.", "title": "Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)" }, { "docid": "MED-4883", "text": "The art of the musical anus is reviewed in the light of its most prominent performers and of anorectal physiological aspects related to this specific musical performance.", "title": "[Flatufonia--or the musical anus]." }, { "docid": "MED-1296", "text": "Natural immunomodulators are getting more and more popular. The popularity, however, often brings over-optimistic claims and mediocre effects. The purpose of the present study was to directly compare eleven most commonly used immunomodulators. Through testing both cellular and humoral branches of immune reactions, we found that most of the immunomodulators tested have limited, if any, effects, with glucan being consistently the most active molecule strongly stimulating every reaction evaluated. These data were also confirmed using a Lewis lung cancer model, where only glucan and resveratrol lowered the number of metastases.", "title": "Natural immunomodulators and their stimulation of immune reaction: true or false?" }, { "docid": "MED-3697", "text": "BACKGROUND: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer. METHODS: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association. RESULTS: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared. CONCLUSIONS: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. IMPACT: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. ©2011 AACR.", "title": "Healthy lifestyle on the risk of breast cancer." }, { "docid": "MED-2276", "text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.", "title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans." }, { "docid": "MED-4097", "text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.", "title": "Green Tea and Breast Cancer" }, { "docid": "MED-3305", "text": "BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.", "title": "Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres." }, { "docid": "MED-2368", "text": "BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.", "title": "Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques." }, { "docid": "MED-2369", "text": "Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.", "title": "Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose" }, { "docid": "MED-5049", "text": "OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.", "title": "Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli..." }, { "docid": "MED-3311", "text": "OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants." }, { "docid": "MED-5050", "text": "Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.", "title": "L-theanine, a natural constituent in tea, and its effect on mental state." }, { "docid": "MED-2357", "text": "Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.", "title": "Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression" }, { "docid": "MED-3153", "text": "This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points", "title": "Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes" }, { "docid": "MED-3924", "text": "PURPOSE: To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. RESULTS: 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P < 0.05). No appreciable change was seen in the placebo group. Serum PSA and testosterone levels were unchanged in both groups. A modest decrease in prostate size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the prostate volume at the end of study with placebo. At 18-month follow-up, only patients who continued therapy, had a favorable treatment variables value. No side effects were identified in either group. CONCLUSION: In the present study, Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.", "title": "Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study." }, { "docid": "MED-4433", "text": "BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.", "title": "Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund." }, { "docid": "MED-3535", "text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.", "title": "Cherries and health: a review." }, { "docid": "MED-3321", "text": "Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.", "title": "Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry." }, { "docid": "MED-3295", "text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.", "title": "Cancer and Noncancer Mortality Among American Seafood Workers" }, { "docid": "MED-4165", "text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.", "title": "Dietary sources and antioxidant effects of ergothioneine." }, { "docid": "MED-4649", "text": "Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens1–3. Aromatase inhibitors therefore constitute a front-line therapy for oestrogen-dependent breast cancer3,4. In a three-step process, each step requiring 1 mol of O2, 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16α-hydroxytestosterone to oestrone, 17β-oestradiol and 17β,16α-oestriol, respectively1–3. The first two steps are C19-methyl hydroxylation steps, and the third involves the aromatization of the steroid A-ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full-length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme’s androgenic specificity and unique catalytic mechanism can be used for developing next-generation aromatase inhibitors.", "title": "Structural basis for androgen specificity and oestrogen synthesis in human aromatase" }, { "docid": "MED-3708", "text": "Asthma is a phenotypically heterogeneous disorder of multifactorial origins that affects 300 million people suffering from asthma and more than 250,000 asthma-related deaths each year. Although treatment for asthma has improved, its prevalence continues to increase, particularly in low and middle income countries, or in some ethnic groups in which prevalence was previously low. Observed spatio-temporal variations in the increased prevalence of asthma depend on exposure to environmental factors. Recently, several arguments are also in favor of the involvement of host susceptibility and stress in the observed increase of asthma prevalence. Further investigations are warranted to better understand mechanisms underlying asthma increase or stagnation. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Is the asthma epidemic still ascending?" }, { "docid": "MED-3306", "text": "OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.", "title": "Farming, growing up on a farm, and haematological cancer mortality." }, { "docid": "MED-1295", "text": "A number of polysaccharides with beta-glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1-->3)-beta-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1-->3)-beta-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the beta-D-glucan chemical structure and transforming it to a soluble form have been published. The beta-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines beta-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of beta-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.", "title": "Natural and modified (1-->3)-beta-D-glucans in health promotion and disease alleviation." }, { "docid": "MED-4880", "text": "BACKGROUND/AIMS: The beneficial or harmful effect of the low-carbohydrate (low-carb), high-protein, high-fat diet (Atkins diet) has not been clearly demonstrated. We determined the effect of a low-carb diet and restricted feeding (70% ad libitum intake) on serum levels of cholesterol, triacylglycerol, glucose, ketone bodies and insulin in rats. METHODS: In experiment 1, each of 4 groups with 10 adult rats was assigned to a high-carb diet (AIN-93G) + ad libitum intake or restricted feeding, or a low-carb diet (53% horsemeat) + ad libitum intake or restricted feeding (2 x 2 factorial). In experiment 2, each of 3 groups with 10 adult rats was assigned to a control (AIN-93G) or low-carb diets (53% beef or horsemeat). RESULTS: Restricted feeding and the low-carb diet reduced (p<0.01) serum triacylglycerol compared with ad libitum intake and the AIN-93G diet, respectively (experiment 1). The dietary effect on serum total cholesterol, high-density or low-density lipid cholesterol appeared to be inconsistent, but restricted feeding increased the low-density lipoprotein cholesterol level. The serum ketone body level was increased by the low-carb diet compared with AIN-93G (experiment 2). CONCLUSION: Restricted feeding and a low-carb diet are beneficial for alleviating cardiovascular disease risk factors, and their effects are additive, restricted feeding being more pronounced. Copyright 2009 S. Karger AG, Basel.", "title": "Effects of very-low-carbohydrate (horsemeat- or beef-based) diets and restricted feeding on weight gain, feed and energy efficiency, as well as ser..." }, { "docid": "MED-3696", "text": "The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.", "title": "Alcohol consumption and breast cancer risk in the Women's Health Study." }, { "docid": "MED-2351", "text": "Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.", "title": "Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum." }, { "docid": "MED-3315", "text": "PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "A pilot case-cohort study of liver and pancreatic cancers in poultry workers." }, { "docid": "MED-3711", "text": "The incidence of autoimmune, allergic and inflammatory disease is increasing due to as yet unidentified environmental factors related to western living conditions. Here, I propose that alterations in the gut microbiome, acting via regulatory T cells (Tregs), may be responsible for this epidemic. Tregs control the threshold for peripheral antigen recognition via tonic downregulation of dendritic cell (DC) costimulation, and are also implicated in maintaining the tolerogenic function of DCs. In this model, minor perturbations in Treg number or function are predicted to lower the activation threshold, allowing proliferation and differentiation of self-reactive CD4T cells of too low an affinity to have undergone negative selection in the thymus. Failure to maintain the tolerogenic commitment of DCs exposed to commensal microbes and allergens could result in potentially pathogenic, allergic and inflammatory responses at epithelial surfaces.", "title": "Regulatory T-cell abnormalities and the global epidemic of immuno-inflammatory disease." }, { "docid": "MED-3918", "text": "The study material consisted of five herbs: chamomile (flowers), mint (leaves), St John's wort (flowers and leaves), sage (leaves) and nettle (leaves), sourced from three producers. The calcium, magnesium, iron, zinc and copper contents were determined for both dried herb samples and prepared infusions, and the extraction rates were calculated. Mineral components were determined using atomic absorption spectrometry. Analysis showed that the contents of individual elements in herbs and infusions depended on the type of raw material, as well as on its origin. Moreover, it was found that iron penetrated the herbal infusions to the lowest degree (4.4-12.4%), while copper did so to the highest (26.7-50.7%). It is felt that in average consumption the herbal infusions are not important as calcium, magnesium, iron, zinc and copper sources in human nutrition.", "title": "Herbal infusions as a source of calcium, magnesium, iron, zinc and copper in human nutrition." }, { "docid": "MED-4916", "text": "Agaritine (N-(gamma-L(+)-glutamyl)-4-hydroxymethyl-phenylhydrazine) was identified and quantified by high-pressure liquid chromatography and used as a marker for the occurrence of phenylhydrazine derivatives in the cultivated Agaricus bitorquis and A. garicus hortensis mushrooms. Although relatively high levels of agaritine (around 700 mg kg(-1)) could be found in freshly harvested A. bitorquis from early flushes, samples from supermarkets contained less agaritine. The content of 28 samples varied between 165 and 457 mg kg(-1), on average being 272 +/- 69 mg kg(-1). The highest amounts of agaritine were found in the skin of the cap and in the gills, the lowest being in the stem. There was no significant difference in agaritine content of the two mushroom species in our study. Pronounced reduction in agaritine content was observed during storage of mushrooms in the refrigerator or freezer, as well as during drying of the mushrooms. The degree of reduction was dependent on the length and condition of storage and was usually in the region 20-75%. No reduction in agaritine content was observed during freeze-drying. Depending on the cooking procedure, household processing of cultivated Agaricus mushrooms reduced the agaritine content to various degrees. Boiling extracted around 50% of the agaritine content into the cooking broth within 5min and degraded 20-25% of the original agaritine content of the mushrooms. Prolonged boiling, as when preparing a sauce, reduced the content in the solid mushroom further (around 10% left after 2h). Dry baking of the cultivated mushroom, a process similar to pizza baking, reduced the agaritine content by approximately 25%, whereas frying in oil or butter or deep frying resulted in a more marked reduction (35-70%). Microwave processing of the cultivated mushrooms reduced the agaritine content to one-third of the original level. Thus, the exposure to agaritine was substantially less when consuming processed Agaricus mushrooms as compared with consuming the raw mushrooms. However, it is not yet known to what extent agaritine and other phenylhydrazine derivatives occurring in the cultivated mushroom are degraded into other biologically active compounds during the cooking procedure.", "title": "Influence of storage and household processing on the agaritine content of the cultivated Agaricus mushroom." }, { "docid": "MED-4650", "text": "Aromatase is a cytochrome P450 enzyme (CYP19) and is the rate limiting enzyme in the conversion of androgens to estrogens. Suppression of in situ estrogen production through aromatase inhibition is the current treatment strategy for hormone-responsive breast cancers. Drugs that inhibit aromatase have been developed and are currently utilized as adjuvant therapy for breast cancer in post-menopausal women with hormone dependent breast cancer. Natural compounds have been studied extensively for important biologic effects such as antioxidant, anti-tumor and anti-viral effects. A significant number of studies have also investigated the aromatase inhibitory properties of a variety of plant extracts and phytochemicals. The identification of natural compounds that inhibit aromatase could be useful both from a chemopreventive standpoint and in the development of new aromatase inhibitory drugs. This review will discuss whole food extracts and the common classes of phytochemicals which have been investigated for potential aromatase inhibitory activity. We will review reported aromatase inhibition, kinetic data and possible structural variations that may inhibit or enhance the interaction of phytochemicals with the aromatase enzyme.", "title": "Phytochemicals for breast cancer prevention by targeting aromatase." }, { "docid": "MED-3705", "text": "The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases.", "title": "Evolution of Inflammatory Diseases" }, { "docid": "MED-2367", "text": "Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.", "title": "Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes." }, { "docid": "MED-3316", "text": "BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.", "title": "An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study." }, { "docid": "MED-3320", "text": "OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.", "title": "Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry." }, { "docid": "MED-2274", "text": "Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.", "title": "Cherry Consumption and the Risk of Recurrent Gout Attacks" }, { "docid": "MED-4719", "text": "Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.", "title": "Tea catechins' affinity for human cannabinoid receptors." }, { "docid": "MED-3699", "text": "BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.", "title": "Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o..." }, { "docid": "MED-3312", "text": "BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.", "title": "Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S." }, { "docid": "MED-4721", "text": "[3H]CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.", "title": "Cannabinoid receptor localization in brain." }, { "docid": "MED-2361", "text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.", "title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York." } ]	[ { "docid": "MED-864", "text": "Hepatotoxic effect related to Ganoderma lucidum (Lingzhi) mushroom powder was first described in a patient from Hong Kong in 2004. In 2005, the authors experienced a case of fatal fulminant hepatitis associated with such a preparation. Both patients had taken other therapeutic agents and traditionally boiled Lingzhi without any toxic effect. After switching to taking Lingzhi in powder form for 1-2 months, the hepatotoxic episode occurred in both patients. The toxic role of Lingzhi powder needs close monitoring in the future, especially in combination with other drugs.", "title": "Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder." }, { "docid": "MED-1592", "text": "The presence of natural estrogen hormones as trace concentrations in the environment has been reported by many researchers and is of growing concern due to its possible adverse effects on the ecosystem. In this study, municipal biosolids, poultry manure (PM) and cow manure (CM), and spent mushroom compost (SMC) were analyzed for the presence of seven estrogen hormones. 17α-estradiol, 17β-estradiol, 17α-dihydroequilin, and estrone were detected in the sampled biosolids and manures at concentrations ranging from 6 to 462 ng/g of dry solids. 17α-estradiol, 17β-estradiol, and estrone were also detected in SMC at concentrations ranging from 4 to 28 ng/g of dry solids. Desorption experiments were simulated in the laboratory using deionized water (milli-Q), and the aqueous phase was examined for the presence of estrogen hormones to determine their desorption potential. Very low desorption of 0.4% and 0.2% estrogen hormones was observed from municipal biosolids and SMC, respectively. An estimate of total estrogen contribution from different solid waste sources is reported. Animal manures (PM and CM) contribute to a significant load of estrogen hormones in the natural environment.", "title": "Occurrence of estrogen hormones in biosolids, animal manure and mushroom compost." }, { "docid": "MED-4713", "text": "INTRODUCTION: Kombucha \"mushroom'' tea is touted to have medicinal properties. Here, we present a case of hyperthermia, lactic acidosis, and acute renal failure within 15 hours of Kombucha tea ingestion. CASE PRESENTATION: A 22 year old male, newly diagnosed with HIV, became short of breath and febrile to 103.0F, within twelve hours of Kombucha tea ingestion. He subsequently became combative and confused, requiring sedation and intubation for airway control. Laboratories revealed a lactate of 12.9 mmol/L, and serum creatinine of 2.1 mg/dL. DISCUSSION: Kombucha tea is black tea fermented in a yeast-bacteria medium. Several case reports exist of serious, and sometimes fatal, hepatic dysfunction and lactic acidosis within close proximity to ingestion. CONCLUSION: While Kombucha tea is considered a healthy elixir, the limited evidence currently available raises considerable concern that it may pose serious health risks. Consumption of this tea should be discouraged, as it may be associated with life-threatening lactic acidosis.", "title": "A case of Kombucha tea toxicity." }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-3683", "text": "BACKGROUND: The aim of this study was to investigate whether consumption of Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) could affect naturally acquired common cold infections in healthy subjects. METHODS: A randomised, parallel, double-blind placebo-controlled study was performed to investigate whether intake of this probiotic mixture could reduce the risk of common cold episodes, number of days with common cold symptoms, frequency and severity of symptoms, and cellular immune response in common cold infections. A total of 272 subjects were supplemented daily with either 10(9) cfu (colony forming units) of probiotics (N = 135) or control (N = 137) for a 12-week period. RESULTS: The incidence of acquiring one or more common cold episode was reduced from 67% in the control group to 55% in the probiotic group (p < 0.05). Also, the number of days with common cold symptoms were significantly (p < 0.05) reduced from 8.6 days in the control group to 6.2 days, in the probiotic group, during the 12-week period. The total symptom score was reduced during the study period from a mean of 44.4 for the control group to 33.6 for the probiotic group. The reduction in pharyngeal symptoms was significant (p < 0.05). In addition, the proliferation of B lymphocytes was significantly counteracted in the probiotic group (p < 0.05) in comparison with the control group. CONCLUSION: In conclusion, intake of the probiotic strains Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) reduces the risk of acquiring common cold infections.", "title": "Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infe..." }, { "docid": "MED-3926", "text": "Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.", "title": "Protein redistribution diet and antiparkinsonian response to levodopa." }, { "docid": "MED-3617", "text": "Background: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, α-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for ≥median compared with <median servings per week of high–vitamin C fruit and vegetables, citrus fruit, and green leafy vegetables were 0.61 (0.43, 0.86), 0.64 (0.46, 0.89), and 0.59 (0.43, 0.81), respectively. The strongest inverse association was observed for ≥median compared with <median combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food: 0.27 (0.14, 0.55). Conclusion: High combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food, or a diet high in their food sources, may protect against cumulative DNA damage in IR-exposed persons.", "title": "High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots" }, { "docid": "MED-1433", "text": "Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.", "title": "Dietary Advanced Glycation End Products and Aging" }, { "docid": "MED-5101", "text": "When making food choices, consumers are faced with the dilemma of reconciling differences between health benefits and exposure to potential toxins. Analyses to estimate likely intake and exposure outcomes for young children and women of child-bearing age shows that seafood, chicken, and beef, while approximately equivalent in protein, vary in key nutrients of importance as well as in levels of certain contaminants. Increasing the variety of choices among meats, poultry, and seafood and consuming them in amounts consistent with current dietary guidelines and advisories will contribute toward meeting nutritional needs while reducing exposure to any single type of contaminant.", "title": "Nutrient and contaminant tradeoffs: exchanging meat, poultry, or seafood for dietary protein." }, { "docid": "MED-954", "text": "It has been speculated that maternal phthalate exposure may affect reproductive development in human newborns. However, the mechanism awaits further investigation. The aim is to evaluate the association between maternal phthalate exposure and cord sex steroid hormones in pregnant women and their newborns from the general population. A total of 155 maternal and infant pair were recruited and analyzed. Levels of urinary phthalate metabolites and sex steroid hormones were determined using liquid chromatography/electrospray tandem mass spectrometry (LC-ESI-MS/MS) and radioimmunoassay (RIA), respectively. No significant correlation was found between each steroid hormones and phthalate metabolites for male newborns, except MMP was marginally significantly correlated with E(2). After adjusting for maternal age, estradiol (E(2)) levels in cord serum from male newborns were not correlated with maternal urinary phthalate metabolites. In female newborns, the maternal urinary levels of mono-(2-ethylhexyl) phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) were negatively correlated with the free testosterone (fT) and fT/E(2) levels in cord serum with Pearson correlation coefficients ranging between -0.24 and -0.29 (p<0.05). Additionally, after gestational age was adjusted, the maternal urinary level of DEHP was negatively correlated with the free testosterone (fT) and fT/E(2) levels in cord serum. We suggest that maternal exposure to phthalates may affect sex steroid hormones status in fetal and newborn stage. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Associations between maternal phthalate exposure and cord sex hormones in human infants." }, { "docid": "MED-4949", "text": "Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.", "title": "Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain" }, { "docid": "MED-2651", "text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.", "title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan." }, { "docid": "MED-3441", "text": "As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Marine edible algae as disease preventers." }, { "docid": "MED-3589", "text": "OBJECTIVE: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN: An observational, analytical case-control study. SETTING: Private fertility clinics. PATIENT(S): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S): We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S): Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.", "title": "Food intake and its relationship with semen quality: a case-control study." }, { "docid": "MED-1031", "text": "Primary (simple) constipation is a consequence of habitual bowel elimination on common toilet seats. A considerable proportion of the population with normal bowel movement frequency has difficulty emptying their bowels, the principal cause of which is the obstructive nature of the recto-anal angle and its association with the sitting posture normally used in defecation. The only natural defecation posture for a human being is squatting. The alignment of the recto-anal angle associated with squatting permits smooth bowel elimination. This prevents excessive straining with the potential for resultant damage to the recto-anal region and, possibly, to the colon and other organs. There is no evidence that habitual bowel elimination at a given time each day contributes considerably to the final act of rectal emptying. The natural behavior to empty the bowels in response to a strong defecation reflex alleviates bowel emptying by means of the recto anal inhibitory reflex.", "title": "Primary constipation: an underlying mechanism." }, { "docid": "MED-3847", "text": "In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.", "title": "Lignans in man and in animal species." }, { "docid": "MED-5320", "text": "Increased (18)F-FDG activity in fatty tissue has previously been reported with PET/CT. We previously named this activity uptake in supraclavicular area fat (\"USA-Fat\"). We and others have speculated that this uptake exists in metabolically active brown adipose tissue (BAT). Such tissue might be expected to have varying metabolic activity depending on the ambient temperature. The purpose of this study was to evaluate the frequency of USA-Fat and its relationship to the outdoor temperature. METHODS: Between July 2001 and June 2002, 1,017 consecutive whole-body scans were obtained with a PET/CT scanner and (18)F-FDG for clinical patients. PET images were reviewed for the presence of USA-Fat. RESULTS: USA-Fat was observed in 68 scans obtained from 62 patients (51 female and 11 male). The incidence of USA-Fat was highest, at 13.7%, in January through March, while outside temperatures were low, and was significantly lower, at 4.1%, during the rest of the year. CONCLUSION: The incidence of USA-Fat is clearly increased during the cooler period of the year. This finding suggests that stimulation by cold temperatures increases the frequency with which USA-Fat occurs, supporting underlying BAT as the etiology for this activity.", "title": "\"USA-Fat\": prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET/CT." }, { "docid": "MED-828", "text": "Background Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. Methods We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Results Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. Conclusion The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.", "title": "Maca (L. meyenii) for improving sexual function: a systematic review" }, { "docid": "MED-4300", "text": "BACKGROUND AND AIMS: Nuts have been part of the human diet since prehistoric times. The aim of the present article is to describe the most important historical and cultural aspects of nut consumption throughout history. DATA SYNTHESIS: We discuss the following historical aspects of nuts originating in the Mediterranean: prehistory, the Egyptian civilization, their spread through the Mediterranean region by the Greek, Phoenician and Roman civilizations, and their reintroduction into Europe by means of the Al-Andalus culture. Particular emphasis is placed on the healthy and nutritional attributes that nuts have had throughout history. We also consider the role of the first globalization of food--the exchange of nuts between continents--and discuss the symbolism that nuts have had for humans throughout history in the context of cultural aspects of the Mediterranean region. CONCLUSIONS: Nuts and fruits are probably the earliest foods consumed by humans and are considered to be important because of their nutritional properties. Nuts have also been used in the past by different civilizations as drugs to prevent or treat several diseases. Copyright © 2010 Elsevier B.V. All rights reserved.", "title": "Cultural and historical aspects of Mediterranean nuts with emphasis on their attributed healthy and nutritional properties." }, { "docid": "MED-5023", "text": "Infection by unicellular green algae has not been described in humans. A case is reported in a 30-year-old woman who developed persistent infection of a healing operative wound on the dorsum of the right foot, after possible contamination by river water while canoeing. The wound was debrided 2 months later. Histologically, infected tissues contained mixed suppurative and granulomatous inflammation associated with endosporulating, round to oval microorganisms, ranging from 6-9 microns in diameter. Many of these organisms contained multiple, strongly periodic acid-Schiff, Gomori methenamine-silver, and Gridley fungus-positive granules in the cytoplasm. The organisms in tissue did not stain with fluorescent antibody conjugates specific for the two known pathogenic Prototheca species. In some organisms, electron microscopy revealed membranous cytoplasmic profiles considered to be remnants of degenerated chloroplasts. These findings are consistent with the presence of a green algal infection.", "title": "Green algal infection in a human." }, { "docid": "MED-2132", "text": "The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected. mTORC1 regulates diverse cellular functions. Several mTORC1 substrates are now known, although in several cases their physiological roles are poorly or incompletely understood. In the case of several processes, although it is clear that they are regulated by mTORC1, it is not known how mTORC1 does this. Lastly, mTORC1 is implicated in ageing, but again it is unclear what mechanisms account for this. Given the importance of mTORC1 signaling both for cellular functions and in human disease, it is a high priority to gain further insights into the control of mTORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.", "title": "mTORC1 signaling: what we still don't know." }, { "docid": "MED-4664", "text": "We report a series of cases of thyroid dysfunction in adults associated with ingestion of a brand of soy milk manufactured with kombu (seaweed), and a case of hypothyroidism in a neonate whose mother had been drinking this milk. We also report two cases of neonatal hypothyroidism linked to maternal ingestion of seaweed made into soup. These products were found to contain high levels of iodine. Despite increasing awareness of iodine deficiency, the potential for iodine toxicity, particularly from sources such as seaweed, is less well recognised.", "title": "Iodine toxicity from soy milk and seaweed ingestion is associated with serious thyroid dysfunction." }, { "docid": "MED-5076", "text": "The objective of the present study was to evaluate the effect of three common cooking practices (i.e., boiling, steaming, and frying) on phytochemical contents (i.e., polyphenols, carotenoids, glucosinolates, and ascorbic acid), total antioxidant capacities (TAC), as measured by three different analytical assays [Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant power (FRAP)] and physicochemical parameters of three vegetables (carrots, courgettes, and broccoli). Water-cooking treatments better preserved the antioxidant compounds, particularly carotenoids, in all vegetables analyzed and ascorbic acid in carrots and courgettes. Steamed vegetables maintained a better texture quality than boiled ones, whereas boiled vegetables showed limited discoloration. Fried vegetables showed the lowest degree of softening, even though antioxidant compounds were less retained. An overall increase of TEAC, FRAP, and TRAP values was observed in all cooked vegetables, probably because of matrix softening and increased extractability of compounds, which could be partially converted into more antioxidant chemical species. Our findings defy the notion that processed vegetables offer lower nutritional quality and also suggest that for each vegetable a cooking method would be preferred to preserve the nutritional and physicochemical qualities.", "title": "Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetables." }, { "docid": "MED-4321", "text": "PURPOSE OF REVIEW: Levels of dehydroepiandrosterone (DHEA) are known to decline with age. In an era of increasing use of supplements to better life, the benefits of DHEA in the aging female population are controversial. The goal of this article is to critically review published studies to determine if there is a role for DHEA supplementation in postmenopausal women. RECENT FINDINGS: Daily administration of oral DHEA achieves serum concentrations similar to those of women in their 20s. Several observational studies have shown that lower DHEA levels are associated with increased cardiovascular risk in women; however, interventional trials show no improvement in atherosclerosis or cardiovascular risk factors, and a lowering of HDL cholesterol levels. DHEA supplementation modestly increases bone mineral density in conjunction with adjuvant therapies and improves cognition in those with mild-to-moderate cognitive impairment, but does not affect cognition in unimpaired women. Use of intravaginal DHEA, but not oral DHEA, alleviates vaginal atrophy and improves sexual function in postmenopausal women. SUMMARY: On the basis of current evidence, there is no role for oral DHEA supplementation in healthy, postmenopausal women. Where benefits have been shown, long-term studies are needed to confirm these benefits and verify the safety profile of DHEA.", "title": "Dehydroepiandrosterone sulfate and postmenopausal women." }, { "docid": "MED-2679", "text": "Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.", "title": "Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice." }, { "docid": "MED-2711", "text": "Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.", "title": "Accidental bullous phototoxic reactions to bergamot aromatherapy oil." }, { "docid": "MED-2089", "text": "In this study, genotoxicity of two mouthwash products (chlorexidin, benzidamine-HCl) were investigated in the Drosophila Wing-Spot Test which makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also, to some extent, to mwh single spots. Recording of the frequency and the size of different spots is allowed for a quantitative determination of the mutagenic and recombinogenic effects. Trans-heterozygous third-instar larvae were treated at different concentrations of the mouthwash products. Chlorexidin exposure concentrations were 0.5, 1 and 2mg/ml. Benzidamine-HCl exposure concentrations were 0.38, 0.75 and 1.5mg/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. Both chlorexidin and benzidamine-HCl were genotoxic in terms of total mutations per wing at the highest doses. Survival rates of flies used in the experiments were significantly lower than those of the control group, with both mouthwash products showing toxic effects on Drosophila melanogaster larvae. Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "title": "Genotoxicity of two mouthwash products in the Drosophila Wing-Spot Test." }, { "docid": "MED-3853", "text": "PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.", "title": "Serum enterolactone and prognosis of postmenopausal breast cancer." }, { "docid": "MED-2258", "text": "Breast cancer is the most prevalent women's cancer, with an age-adjusted incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic pollutant with multiple biological effects, has been reported to be associated with breast cancer in one US regional case-control study. We examined the association of breast cancer with urinary cadmium (UCd), in a case-control sample of women living on Long Island (LI), NY (100 with breast cancer and 98 without), a region with an especially high rate of breast cancer (142.7 per 100,000 in Suffolk County) and in a representative sample of US women (NHANES 1999-2008, 92 with breast cancer and 2,884 without). In a multivariable logistic model, both samples showed a significant trend for increased odds of breast cancer across increasing UCd quartiles (NHANES, p=0.039 and LI, p=0.023). Compared to those in the lowest quartile, LI women in the highest quartile had increased risk for breast cancer (OR=2.69; 95% CI=1.07, 6.78) and US women in the two highest quartiles had increased risk (OR=2.50; 95% CI=1.11, 5.63 and OR=2.22; 95% CI=.89, 5.52, respectively). Further research is warranted on the impact of environmental cadmium on breast cancer risk in specific populations and on identifying the underlying molecular mechanisms.", "title": "Environmental cadmium and breast cancer risk" }, { "docid": "MED-1571", "text": "One hundred and fifty-nine ichtyosarcotoxic outbreaks, including 477 people, were recorded in the island of Réunion (SW Indian ocean) between 1986 and 1994. Ciguatera outbreaks represented 78.6% of the total cases and its annual incidence rate was estimated to be 0.78/10,000 residents. Symptoms caused by ciguatera poisoning are not different from those reported in Pacific and Caribbean islands, except for the additional symptoms of hallucinatory poisoning in 16% of the patients. Serranidae fish, including species of great commercial value, were the most commonly incriminated accounting for 50% of the outbreaks.", "title": "Ciguatera in Réunion Island (SW Indian Ocean): epidemiology and clinical patterns." } ]
1962	Where can I borrow money for investing?	[ { "docid": "121161", "text": "Borrow money and start a business. Follow your business plan and invest in yourself and your entrepreneurship. If you mean invest in the market, do not borrow money. In your plan, you are willing to make payments right? There are lots of things you can do better, but borrowing money to invest in the market for a couple of years is not one of them. Investing is boring, saving is boring, and planning your financial future is boring. It takes a consistent effort and you aren't going to get rich quick.", "title": "" }, { "docid": "179103", "text": "If you are looking for money to speculate in the capital markets, then your brokers will already lend to you at a MUCH more favorable rate than an outside party will. For instance, with $4,000 you could EASILY control $40,000 with many brokers, at a 1% interest rate. This is 10:1 leverage, much like how US banks operate... every dollar that you deposit with them, they speculate with 10x as much. Interactive Brokers will do this for you with your current credit score. They are very reputable and clear through Goldman Sachs, so although reputable is subjective in the investment banking world, you won't have to worry the federal government raiding them or anything. If you are investing in currencies than you can easily do 50:1 leverage as an American, or 100:1 as anyone else. This means with only $400 dollars you can control $40,000 account. If you are investing in the futures market, then there are many many ways to double and triple and quadruple your leverage at the lowest interests rates. Any contract you enter into is a loan from the market. You have to understand, that if you did happen to have $40,000 of your own money, then you could get $4,000,000 account size for speculating, at 1% interest. Again, these are QUICK ways to lose your money and owe a lot more! So I'd really advise against it. A margin call in the futures market can destroy you. I advise you to just think more efficiently until you come up with a way to earn that much money initially, and then speculate.", "title": "" }, { "docid": "233805", "text": "\"Borrowing to invest is almost always a bad idea. You'd have to take out an unsecured loan, which has a higher interest rate, or a secured loan and put at risk whatever you are securing the loan with. You need some means to make payments on the loan, or if interest is being added to the balance then take the compounding effect into account with regards to the cost of the money and how much you will really end up owning. In order to come out ahead you need to 'invest' in something that will yield a return that is higher than the cost of borrowing the money, such high yields always come with higher risk, meaning that you will actually GET that return is less and less of a sure thing.. so now you are talking about the 'chance' to make money, Or a chance your 'investment' could fail, perhaps badly. Meaning you could well do nothing but end up in debt with little to nothing to show for it. If someone claims to have a 'sure thing' and is encouraging you to borrow money to invest in it, I'd be checking their back for a fin and remembering the lyrics \"\"when the shark bites ... scarlet billows start to spread\"\"\"", "title": "" }, { "docid": "290325", "text": "Have you considered social lending (for example: Lending Club)?", "title": "" }, { "docid": "212308", "text": "\"The question should read: \"\"Borrow huge money for speculating\"\". This is a bad idea on many levels. The lowest rates available will be from time-limited credit card offers, followed by broker margin accounts. Personal loans are going to be higher. My advice: if you insist on throwing your money away, go to Vegas with $40k. At least you'll get some complimentary food and drink.\"", "title": "" } ]	[ { "docid": "557324", "text": "There are a few reasons, particularly for businesses. The first is opportunity cost. That chunk of money they have could be used to get higher returns somewhere else. If they can borrow from a bank at low interest rates to finance their ongoing operations, they can use their cash to get a higher return somewhere else. The second is credit rating. For public companies, ratings companies give high emphasis to companies with large reserves. This strengthens their ability to pay back the loan should it become necessary. A good credit rating in turn let's the company borrow money at lower rates. When a company can borrow money at low rates, it circles back to the first point where they can now put their reserves to better use. The third is leverage. Companies can use the cash they have built up to leverage into a larger investment. Assuming the investment works out, it will pay for the cost of borrowing over time. For instance let's say I have $1 million to invest. I can pay all cash for a $1 million apartment building or I can leverage that into a $3 million building. Assuming I run it well, the tenants will pay for the cost of borrowing $2 million and at the end of the term I'll be left with my $3 million building.", "title": "" }, { "docid": "293897", "text": "\"Let me run some simplistic numbers, ignoring inflation. You have the opportunity to borrow up to 51K. What matters (and varies) is your postgraduation salary. Case 1 - you make 22K after graduation. You pay back 90 a year for 30 years, paying off at most 2700 of the loan. In this case, whether you borrow 2,800 or 28,000 makes no difference to the paying-off. You would do best to borrow as much as you possibly can, treating it as a grant. Case 2 - you make 100K after graduation. You pay back over 7K a year. If you borrowed the full 51, after 7 or 8 years it would be paid off (yeah, yeah, inflation, interest, but maybe that might make it 9 years.) In this case, the more you borrow the more you have to pay back, but you can easily pay it back, so you don't care. Invest your sponsorships and savings into something long term since you know you won't be needing to draw on them. Case 3 - you make 30K after graduation. Here, the payments you have to make actually impact how much disposable income you have. You pay back 810 a year, and over 30 years that's about 25K of principal. It will be less if you account for some (even most) of the payment going to interest, not principal. Anything you borrow above 25K (or the lower, more accurate amount) is \"\"free\"\". If you borrow substantially less than that (by using your sponsorship, savings, and summer job) you may be able to stop paying sooner than 30 years. But even if you borrow only 12K (or half the more accurate number), it will still be 15 years of payments. Running slightly more realistic versions of these calculations where your salary goes up, and you take interest into account, I think you will discover, for each possible salary path, a number that represents how much of your loan is really loan: everything above that is actually a grant you do not pay back. The less you are likely to make, the more of it is really grant. On top of that, it seems to me that no matter the loan/grant ratio, \"\"borrow as much as you can from this rather bizarre source\"\" appears to be the correct answer. In the cases where it's all loan, you have a lot of income and don't care much about this loan payment. Borrowing the whole 51K lets you invest all the money you get while you're a student, and you can use the returns on those investments to make the loan payments.\"", "title": "" }, { "docid": "474318", "text": "\"If the government prints money recklessly and causes inflation, people will come to expect inflation, and the value of the currency will plummet, and you'll end up like Zimbabwe where a trillion dollars won't buy a loaf of bread. If the government actually pays people for the money they borrow, they don't have this problem - and as it turns out, the US government can get pretty good rates on borrowing in general, in part because they're extraordinarily good about paying them back. (Also, inflation expectations are low, so people will accept 1-2% interest rates. If you expected inflation of 10%, you'd see people demanding something more like 12% interest rates.) (The downside of too much of this sort of borrowing is that it \"\"crowds out\"\" other borrowing, which may harm the economy. Who would lend money to / invest in a small business, if the government is paying good money and there's almost no risk at all?) Now, inflation can come into play afterward, if the Fed decides it needs to maintain \"\"easy money\"\" policies to stimulate the economy (because taxes are too high because we're paying off the debt, or because we've crowded out smaller borrowers, or something). -- In general, you can count on the the principle that if you, as the government, try to play too many games with people's money... well, people aren't stupid; they will eventually catch on, and adjust their behavior to compensate, and then you're right back where you started, but with less trust.\"", "title": "" }, { "docid": "24702", "text": "It looks like your Solo 401K loan will need to repaid in 5 years. If you borrow too much in order to pay back in this time you run into the typical 401K loan risks, that it is considered a distribution. Don't borrow more then can be repaid in that time. When you borrow money from your 401K, it is no longer invested in the market. Lets assume that you are borrowing at 6% or so, and your LOC is at 3.5%, and the mutual funds you are invested in are returning 9%. You would be better off with the LOC. As you are paying 3.5% but earning 9%. Keep in mind with a LOC that is variable you have interest rate risk, where you don't really have that with the 401K loan. I think the 401K loan is riskier then you are allowing. If you do not pay it back within the allotted time, you get nailed for 40% of the unpaid balance. That is quite high. With the HELOC, you can weather quite a few negative credit events without your home ever being in jeopardy.", "title": "" }, { "docid": "24917", "text": "Voluntarily assuming a loan is a bad idea, especially for a non-investment purpose. It would be one thing to take on a loan to operate a business or buy a piece of capital equipment, like a machine that would make you money. Borrowing money to have a more luxurious house is foolish. The smart move is to buy a good quality home that will meet your needs for as little as possible. Having $800,000 leaves a quit a bit of leeway in that department. You don't say where you live, but if this occurred in my area (eastern Massachusetts) I would buy a house for $500,000 and then invest the remaining $300,000. If I lived in the California bay area, it might be necessary to spend the whole $800,000. Either way there should be no need to borrow money. Also, if you buy a house for cash, often you can get a substantially better deal than if you have to involve a bank. Not owing anyone money is a huge psychological advantage in business and in life in general. View being debt-free as a springboard to success and happiness.", "title": "" }, { "docid": "126949", "text": "I think you are a little confused. If you have 10.000€ in cash for a car, but you decide instead to invest that money and take out a loan for the car at 2,75% interest, you would have to withdraw/sell 178€ each month from your investment to make your loan payment. If you made exactly 2,75% on your investment, you would be left with 0€ in your investment when the loan was paid off. If your investment did better than 2,75%, you would come out ahead, and if your investment did worse than 2,75%, you would have lost money on your decision. Having said all that, I don't recommend borrowing money to buy a car, especially if you have that amount of cash set aside for the car. Here are some of the reasons: Sometimes people feel better about spending large amounts of money if they can pay it off over time, rather than spending it all at once. They tell themselves that they will come out ahead with their investments, or they will be earning more later, or some other story to make themselves feel better about overspending. If getting the loan is allowing you to spend more money on a car than you would spend if you were paying cash, then you will not come out ahead by investing; you would be better off to spend a smaller amount of money now. I don't know where you are in the world, but where I come from, you cannot get a guaranteed investment that pays 2,75%. So there will be risk involved; if the next year is a bad one for your investment, then your investment losses combined with your withdrawals for your car payments could empty your investment before the car is paid off. Conversely, by skipping the 2,75% loan and paying cash for your car, you have essentially made a guaranteed 2,75% on this money, comparatively speaking. I don't know what the going rate is for car loans where you are, but often car dealers will give you a low loan rate in exchange for a higher sales price. As a result, you might think that you can easily invest and beat the loan rate, but it is a false comparison because you overpaid for the car.", "title": "" }, { "docid": "504479", "text": "Good question. If a person has a choice, it is probably better to pay cash. But not always. If your large pile of cash can earn more being invested than cost of the interest to borrow a similar large pile of cash, it is beneficial to get a mortgage. Otherwise pay cash. EXAMPLE: A house costs $100,000. I have $100,000 in extra money. I can invest that at 5% per year, and I can borrow an additional $100,000 at 2% per year. Since I can make more on my pile of cash than it costs to borrow another pile of cash, borrowing is better. Compound interest is the most powerful force on the planet according to Albert Einstein (maybe). That isn't likely for most people though. Here is the results from some online financial calculators. http://www.calcxml.com/do/hom03 Borrowing $100,000 with 2% interest for 30 years will cost a total of $148.662. You get $100,000, but it cost you $48,662 to do it. http://www.calcxml.com/do/sav07 Saving $100,000 in a bank account with an interest rate of %5 will be worth $432,194 in 30 years. By not spending the money you will earn $332,194 over the course of 30 years. So if you can invest at 5% and borrow at 2% you will end up with $283,532 more than if you didn't. It is a pretty extreme example, and financial advisers make a lot of money figuring out the complex nature of money to make situations like that possible.", "title": "" }, { "docid": "554814", "text": "\"I don't follow the numbers in your example, but the fundamental question you're asking is, \"\"If I can borrow money for a low cost, and if I think I can invest it and receive returns greater than that cost, should I do it?\"\" It doesn't matter where that money comes from, a mortgage that's bigger than it needs to be, a credit card teaser rate, or a margin line from your stock broker. The answer is \"\"maybe\"\" - depending on the certainty you have about the returns you'd receive on your investments and your tolerance for risk. Only you can answer that question for yourself. If you make less than your mortgage rates on the investments, you'll wish you hadn't! As an aside, I don't know anything about Belgian tax law, but in US tax law, your deductions can be limited to the actual value of the home. Your law may be similar and thus increase the effective mortgage interest rate.\"", "title": "" }, { "docid": "325118", "text": "\"Mortgage interest in Canada is not generally tax deductible for individuals. (Where did you read otherwise?) As an individual, the only mortgage interest you may be able to deduct is when you borrow the money to purchase an income-producing asset, e.g another property you can rent out, or investments producing dividends or other income. In these cases, the interest you pay on the borrowed funds, i.e. the \"\"carrying costs\"\" for your investments, would be deductible against the income produced by the investments purchased.\"", "title": "" }, { "docid": "402325", "text": "\"> So I asked this question in /r/DebateaCommunist and got some interesting answers, mostly about how banks exist to make money out of nowhere and to fool people. What do yall have to say? That isn't what they said. Nobody mentioned fooling people from what I can see from a cursory glance. And if they did, they're being facetious. Also, they didn't mean \"\"make money from thin air\"\" in the sense of it being a magical trick. They make money from a sort of market inefficiency: they broker between people who want to invest money and those who want to borrow it. The top two answers are about right: a bank borrows money from investors (who deposit money in checking and savings accounts), and lends it to borrowers in the form of loans or mortgages. The difference between the interest rates is their profit. You deposit $1000 with me at 2% for 20 years. I give you $1485.95 at the end of that term. Where did I get the extra five hundred books? Well I lent it out in mortgages over the same terms at 6% and received $3207.14 over the same period of time. Your $1000 made you $485.95, and made me $1721.19 which I keep for the purposes of providing you with ATMs, dealing with bad debts and staffing the place. Simple, eh? Of course, they also provide other services in addition to this, and the way in which they do it is regulated, but that's all a bank is at its core. A central bank is slightly different: they issue money (i.e. \"\"print\"\" it), and supply it at a headline interest rate to the commercial banks. And of course banks borrow amongst themselves. But then we get ourselves down the rabbit hole of \"\"grown up\"\" economics and LIBOR and the like... there are whole textbooks used to explain exactly how that mechanism works and what's going on there. But if you want to get rich, find a way to start a bank. Seriously. Doing it to the old school way is seriously profitable if you can be trusted.\"", "title": "" }, { "docid": "559363", "text": "I've spent enough time researching this question where I feel comfortable enough providing an answer. I'll start with the high level fundamentals and work my way down to the specific question that I had. So point #5 is really the starting point for my answer. We want to find companies that are investing their money. A good company should be reinvesting most of its excess assets so that it can make more money off of them. If a company has too much working capital, then it is not being efficiently reinvested. That explains why excess working capital can have a negative impact on Return on Capital. But what about the fact that current liabilities in excess of current assets has a positive impact on the Return on Capital calculation? That is a problem, period. If current liabilities exceed current assets then the company may have a hard time meeting their short term financial obligations. This could mean borrowing more money, or it could mean something worse - like bankruptcy. If the company borrows money, then it will have to repay it in the future at higher costs. This approach could be fine if the company can invest money at a rate of return exceeding the cost of their debt, but to favor debt in the Return on Capital calculation is wrong. That scenario would skew the metric. The company has to overcome this debt. Anyways, this is my understanding, as the amateur investor. My credibility is not even comparable to Greenblatt's credibility, so I have no business calling any part of his calculation wrong. But, in defense of my explanation, Greenblatt doesn't get into these gritty details so I don't know that he allowed current liabilities in excess of current assets to have a positive impact on his Return on Capital calculation.", "title": "" }, { "docid": "358736", "text": "Companies with existing borrowings (where borrowings are on variable interest rates) or in the case with fixed interest rates - companies that get new borrowings - would pay less interest on these borrowings, so their cost will go down and profits up, making them more attractive to investors. So, in general lower interest rates will make the share market a more attractive investment (than some alternatives) as investors are willing to take on more risk for potentially higher returns. This will usually result in the stock market rising as it is currently in the US. EDIT: The case for rising interest rates A central bank's purpose when raising interest rates is to slow down an economy that is booming. As interest rates rise consumers will tighten up their spending and companies will thus have less revenue on top of higher costs for maintaining existing borrowing (with variable rates) or new borrowing (with fixed rates). If rates are higher companies may also defer new borrowings to expand their business. This will eventually lead to lower profits and lower valuation for these companies. Another thing that happens is that as banks start increasing interest for saving accounts investors will look for safety where they can get a higher return (than before) without the risk of the stock market. With lowering profits and valuations, and investor's money flowing out of shares and into the money market, so will company share prices drop (although this may lag a bit with the share market still booming due to greed. But once the boom stops watchout for the crash).", "title": "" }, { "docid": "385139", "text": "If you take the statement you quote as stated, it is indeed absurd. Unless you have a really creative tax accountant or live in a country with very unusual tax laws, any tax deduction you get for mortgage interest is going to be less than the interest. You don't come out ahead by getting a $25 deduction if you had a $100 expense to get that deduction. Where there can be some sense behind such a statement is if you consider the alternative to paying cash for a house or making extra payments against a mortgage. If you had $100,000 in cash in a box under your bed, and the choice is between, (a) use that $100,000 to buy a house in cash, or (b) borrow $100,000 at 6% interest and leave that cash in the box under the bed, than clearly (a) is the better choice because it saves you the interest expense. But if the choice is between, (a) buy a house for $100,000 in cash and borrow $100,000 at 6% to buy a car; or (b) borrow $100,000 at 6% interest to buy a house and use the $100,000 cash to buy the car, (b) is the better choice. The home mortgage loan is tax deductible; the car loan is not. As others have pointed out, if instead of using some extra cash to pay down the principle on your mortgage you used that money to invest in the stock market, it is likely that you would get better returns on the investment than what you would have saved in interest on the mortgage -- depending, of course, on how the market is doing and how well you pick stocks. But the key issue there isn't the tax deduction, it's the comparison of the profits from the investment versus the opportunity cost of the money that could have been saved on the mortgage interest. The tax deduction affects that comparison by effectively reducing the interest rate on the mortgage -- your real interest expense is the nominal interest minus the deduction -- but that's not the key point, just another number to plug in to the formula. By the way, given the complexity of U.S. tax law, I would not rule out the possibility that there could be some scenario where you really would save money by having mortgage interest. There are lots of deductions and credits that are phased out or eliminated as your income goes up. Perhaps you could find some set of tax laws that apply to you such that having an additional $1000 in interest expense lets you take a $300 deduction here and a $500 credit there, etc, and they add up to more than $1000. I don't know if that could actually happen, but the rules are complicated enough that, maybe. Any tax accountants here who can come up with such a scenario?", "title": "" }, { "docid": "400910", "text": "\"Average return on the S&P500 over the last 10 years has been 1.6 %; so if you'd invested in that with money borrowed at 3 % you would have lost (so far). Investing with borrowed money implies you think you can beat the market: that you're a cleverer investor than whoever decided to lend you the money. Whoever decided to lend you the money decided that you are the best (return/risk ratio) investment for their money. It might make sense to invest borrowed money if you don't need to pay it back if things go wrong: if you're an investment professional whose bonus depends on the profit you make, but who won't need to repay any loss. It might also makes sense to borrow money if you're going to 'add value', e.g. sweat equity: for example if you use it to renovate a house or (if you're a business) to hire more staff. But the question was \"\"What guidelines do you use\"\" and the answer is, \"\"I don't make passive investments with borrowed money.\"\" My Dad did it, i.e. didn't repay his mortgage as soon as he could have: but that was because (back in the '70s) he had a long-term (government-sponsored) mortgage for about 1.5 % (designed to help first-time buyers or something like that), at a time when banks were paying higher interest rates on (ultra-safe) deposits.\"", "title": "" }, { "docid": "582161", "text": "\"As others have pointed out, leveraged investing is investing borrowed money. To do so, you need to convince a lender that you're good for the loan. This usually means you need to have collateral worth what you're trying to borrow, or you need to pay a higher rate to account for the fact that they're gambling that you will remain employed and pay off the loan. Leveraged investing is, in general, a risky move for exactly this reason. You can lose not just your original investment, but everything you borrowed as well. The only time it really makes sense, in my admittedly conservative opinion, is when you (a) can afford to suffer that loss, (b) are pretty confident of your investment, and (c) have assets which you have no intention to sell for the duration of the loan. An \"\"unneeded\"\" mortgage on a house is a classic example, thusly: When I purchased my house, I had enough savings that I could have bought it without taking a mortgage. Instead, I took out a mortgage for a large part of that, and left the remainder in my investment accounts -- essentially building the leveraging loan into the mortgage. I then got obscenely \"\"lucky\"\" when interest rates fell through the floor due to the Great Recession, and was able to refinance the mortgage to near record low rates. As a result, on that loan -- which, as I say, I'm in the position of being able to pay off at any time without killing my finances -- I'm currently paying about 3.5%, while the cash this has let me leave in my investments is earning several times that... a net win. But again, note that this required collateral. Essentially, all I'm doing is paying a bit to to borrow my own money (part of the value of the house). There really is no easy way to \"\"convert 25k to 250k\"\" -- if there was, everyone would be doing it. There's no magic in investment. Just time and compounding returns and trading off risk against potential gain. The more you try to push it and win big, the more you risk losing big. I really recommend not attempting anything fancy until you're wealthy enough that you can afford those losses. But if you insist on playing in this space, the answer to your question is to buy options. Options are a packaged form of borrowing to invest. Note that they're still considered high-risk unless you know EXACTLY what you're doing, and again I strongly recommend you not put money into them unless you can afford to lose it -- options have a nasty habit of turning from apparent gains on paper to losses remarkably quickly.\"", "title": "" }, { "docid": "505172", "text": "The answer is mathematics. Let's say you have $100 capital to invest with.. With a mortgage: With a unit trust (assuming you don't put in borrowed money): 5% growth on the property is $25, but a $25 profit on a unit trust requires 25% growth. Well, that's assuming zero interest and zero fees. Let's say interest is 3% but so are trust fees. A property now requires 8% growth for $25 profit in a year, where a unit trust now requires 29% growth for $25 profit. Which one is more likely? The above calculations don't take in to consideration all associated costs and is obviously exaggerated but it shows the answer is not black and white but is instead just mathematics on a bunch of variables. Debt isn't a bad thing so don't be afraid of using debt. With debt you can borrow more to invest. Having a fully paid off house is not a good investment if some of that equity could be earning you more else where (if the math makes sense).", "title": "" }, { "docid": "401753", "text": "Actually, share holder value is is better maximised by borrowing, and paying dividends is fairly irrelevant but a natural phase on a mature and stable company. Company finance is generally a balance between borrowing, and money raised from shares. It should be self evident with a little thought that if not now, then in the future, a company should be able to create earnings in excess of the cost of borrowing, or it's not a very valuable company to invest in! In fact what's the point of borrowing if the cost of the interest is greater than whatever wealth is being generated? The important thing about this is that money raised from shares is more expensive than borrowing. If a company doesn't pay dividends, and its share price goes up because of the increasing value of the business, and in your example the company is not borrowing more because of this, then the proportion of the value of the company that is based on the borrowing goes down. So, this means a higher and higher proportion of the finance of a company is provided by the more expensive share holders than the less expensive borrowing, and thus the company is actually providing LESS value to share holders than it might. Of course, if a company doesn't pay a dividend AND borrows more, this is not true, but that's not the scenario in your question, and generally mature companies with mature earnings may as well pay dividends as they aren't on a massive expansion drive in the same way. Now, this relative expense of share holders and borrowing is MORE true for a mature company with stable earnings, as they are less of a risk and can borrow at more favourable rates, AND such a company is LIKELY to be expanding less rapidly than a small new innovative company, so for both these reasons returning money to share holders and borrowing (or maintaining existing lending facilities) maintains a relatively more efficient financing ratio. Of course all this means that in theory, a company should be more efficient if it has no share holders at all and borrows ALL of the money it needs. Yes. In practise though, lenders aren't so keen on that scenario, they would rather have shareholders sharing the risk, and lending a less than 100% proportion of the total of a companies finance means they are much more likely to get their money back if things go horribly wrong. To take a small start up company by comparison, lenders will be leary of lending at all, and will certainly impose high rates if they do, or ask for guarantors, or demand security (and security is only available if there is other investment besides the loan). So this is why a small start up is likely to be much more heavily or exclusively funded by share holders. Also the start up is likely not to pay a dividend, because for a start it's probably not making any profit, but even if it is and could pay a dividend, in this situation borrowing is unavailable or very expensive and this is a rapidly growing business that wants to keep its hands on all the cash it can to accelerate itself. Once it starts making money of course a start up is on its way to making the transition, it becomes able to borrow money at sensible rates, it becomes bigger and more valuable on the back of the borrowing. Another important point is that dividend income is more stable, at least for the mature companies with stable earnings of your scenario, and investors like stability. If all the income from a portfolio has to be generated by sales, what happens when there is a market crash? Suddenly the investor has to pay, where as with dividends, the company pays, at least for a while. If a company's earnings are hit by market conditions of course it's likely the dividend will eventually be cut, but short term volatility should be largely eliminated.", "title": "" }, { "docid": "441518", "text": "\"A good question -- there are many good tactical points in other answers but I wanted to emphasize two strategic points to think about in your \"\"5-year plan\"\", both of which involve around diversification: Expense allocation: You have several potential expenses. Actually, expenses isn't the right word, it's more like \"\"applications\"\". Think of the money you have as a resource that you can \"\"pour\"\" (because money has liquidity!) into multiple \"\"buckets\"\" depending on time horizon and risk tolerance. An ultra-short-term cushion for extreme emergencies -- e.g. things go really wrong -- this should be something you can access at a moment's notice from a bank account. For example, your car has been towed and they need cash. A short-term cushion for emergencies -- something bad happens and you need the money in a few days or weeks. (A CD ladder is good for this -- it pays better interest and you can get the money out quick with a minimal penalty.) A long-term savings cushion -- you might want to make a down payment on a house or a car, but you know it's some years off. For this, an investment account is good; there are quite a few index funds out there which have very low expenses and will get you a better return than CDs / savings account, with some risk tolerance. Retirement savings -- $1 now can be worth a huge amount of money to you in 40 years if you invest it wisely. Here's where the IRA (or 401K if you get a job) comes in. You need to put these in this order of priority. Put enough money in your short-term cushions to be 99% confident you have enough. Then with the remainder, put most of it in an investment account but some of it in a retirement account. The thing to realize is that you need to make the retirement account off-limits, so you don't want to put too much money there, but the earlier you can get started in a retirement account, the better. I'm 38, and I started both an investment and a retirement account at age 24. They're now to the point where I save more income, on average, from the returns in my investments, than I can save from my salary. But I wish I had started a few years earlier. Income: You need to come up with some idea of what your range of net income (after living expenses) is likely to be over the next five years, so that you can make decisions about your savings allocation. Are you in good health or bad? Are you single or do you have a family? Are you working towards law school or medical school, and need to borrow money? Are you planning on getting a job with a dependable salary, or do you plan on being self-employed, where there is more uncertainty in your income? These are all factors that will help you decide how important short-term and long term savings are to your 5-year plan. In short, there is no one place you should put your money. But be smart about it and you'll give yourself a good head start in your personal finances. Good luck!\"", "title": "" }, { "docid": "179679", "text": "\"Some very general advice. Lifestyle borrowing is almost always a bad idea. You should limit your borrowing to where it is an investment decision or where it is necessary and avoid it when it is a lifestyle choice. For example, many people need to borrow to have a car/house/education or go without. Also, if you are unemployed for a long period of time and can't find work, charging up the credit cards seems very reasonable. However, for things like entertainment, travel, and other nice-to-haves can easily become a road to crushing debt. If you don't have the cash for these types of things, my suggestion is to put off the purchase until you do. Note: I am not including credit cards that you pay off in full at the end of the month or credit used as a convenience as \"\"borrowing\"\"\"", "title": "" }, { "docid": "18449", "text": "\"It's all about access to capital: You can borrow against 401ks up to an extent. You can borrow against CDs outside of tax sheltered retirement plans. You can't borrow against an IRA, although there is a situation with a very small time frame that would still be state sanctioned with no tax penalties. I wouldn't recommend it. Annuities come with penalties. I've looked at many possibilities of accessing retirement capital without penalty, and 401k's offer that ability, but its also good to just have savings accounts and investments that are not tax-deferred. Borrowing against 401k pros: http://www.ehow.com/how_2075551_borrow-money-from-401k.html cons: http://www.investopedia.com/articles/retirement/06/eightreasons401k.asp#axzz29TtJPoXO Outside of your general expenses and play money, money you put toward - say... - a house should be non-tax deferred. Because if you like borrowing, you can always borrow against the house, or any property. The root of the problem is liquidity and access to capital, understanding those fundamental concepts will answer most questions. \"\"Am I liquid? Yes/No\"\" \"\"Can I be liquid without losing money? Yes/No\"\" As usual, more is more, adjust your priorities accordingly.\"", "title": "" }, { "docid": "67406", "text": "They are wrong. Agreed. The problem I have is that sooner or later you get in so much debt no one will lend money to you anymore. At that point austerity is forced on you. The increased spending comes from domestic and foreign investors. We all know how fickle the financial markets can be. If our debt gets too high and they cut off the tap, we are fucked. I don't think we are anywhere near that point now. However, things can change dramatically in the course of a few months. Political tensions, global uncertainty and social unrest could all cause enough of a panic that people start questioning the safety of U.S. treasuries. We could also see the day where everyone collectively demands the U.S. stop ripping them off with negative bond yields. Like I said, I see no indication of that now, but who knows how long it will take? I know this is a bit of a tangent, but it is clear. My solution: borrow money to improve the economy while you can but make sure that your dollars count to fixing the economy. Otherwise, you are going to be stuck with a stagnant economy AND at a serious risk of bankruptcy when the financial markets no longer see you as a wise investment. You can't save yourself from falling off of two cliffs at the same time so our politicians should stop dicking around and start looking for real solutions with the money they are borrowing instead of pissing it away on useless shit.", "title": "" }, { "docid": "314478", "text": "\"And what exactly do I profit from the short? I understand it is the difference in the value of the stock. So if my initial investment was $4000 (200 * $20) and I bought it at $3800 (200 * $19) I profit from the difference, which is $200. Do I also receive back the extra $2000 I gave the bank to perform the trade? Either this is extremely poorly worded or you misunderstand the mechanics of a short position. When you open a short position, your are expecting that the stock will decline from here. In a short position you are borrowing shares you don't own and selling them. If the price goes down you get to buy the same shares back for less money and return them to the person you borrowed from. Your profit is the delta between the original sell price and the new lower buy price (less commissions and fees/interest). Opening and closing a short position is two trades, a sell then a buy. Just like a long trade there is no maximum holding period. If you place your order to sell (short) 200 shares at $19, your initial investment is $3,800. In order to open your $3,800 short position your broker may require your account to have at least $5,700 (according to the 1.5 ratio in your question). It's not advisable to open a short position this close to the ratio requirement. Most brokers require a buffer in your account in case the stock goes up, because in a short trade if the stock goes up you're losing money. If the stock goes up such that you've exhausted your buffer you'll receive what's known as a \"\"margin call\"\" where your broker either requires you to wire in more money or sell part or all of your position at a loss to avoid further losses. And remember, you may be charged interest on the value of the shares you're borrowing. When you hold a position long your maximum loss is the money you put in; a position can only fall to zero (though you may owe interest or other fees if you're trading on margin). When you hold a position short your maximum loss is unlimited; there's no limit to how high the value of something can go. There are less risky ways to make short trades by using put options, but you should ensure that you have a firm grasp on what's happening before you use real money. The timing of the trades and execution of the trades is no different than when you take a plain vanilla long position. You place your order, either market or limit or whatever, and it executes when your trade criteria occurs.\"", "title": "" }, { "docid": "360003", "text": "My opinion is that in general, it is probably not a good idea to borrow at a cost in order to make your RRSP contribution. Banks, of course, have an interest in loaning you money. Don't expect their literature to be objective on the matter! They are selling you a product and the advice is biased. What better way to double-dip than to get guaranteed interest payments from you, as well as ongoing fees for (probably also) getting your loan money invested in their high-fee mutual funds? A year's RRSP contribution room allowance isn't use it or lose it — unlike 401k contribution allowances in the U.S.. That is, unused RRSP contribution room accumulates and you can take advantage of it in later years. If we couldn't carry our RRSP contribution room over, I might feel different about the general case for RRSP loans. Yet there are two specific cases I can think of where it may make sense to borrow and pay back: (a possible case) ... if your tax rate is currently in a high bracket (e.g. 46%), and you anticipate being in a lower income and bracket next year (e.g. 35%), then it would make sense to take advantage of the higher tax savings in the current tax year. If you waited until the following year to take the deduction, you'd lose out on 11% of the deducted amount. For a typical person whose income is level or increasing from year to year, this isn't likely to be applicable, but it could help somebody who is going on leave or otherwise has irregular income. (a foolish case) ... if you knew, somehow, that you could realize a return on your invested RRSP money exceeding the pre-tax earnings required to pay the interest on the RRSP loan. However, I would suggest this is foolish bet to make. The interest you pay is guaranteed, but the return you are expected to get is probably not (or if it is, it is probably a return lower than what your bank wants to charge on the loan.) If for some reason it does make sense for you, take the money and invest it somewhere better than the high-fee mutual funds the bank is also pushing.", "title": "" }, { "docid": "380387", "text": "People are downvoting you, but the reality is that a cushion isn't a bad idea. Not a perpetual thing, but until the OP gets set up with a job place to live etc. They know the job is going to work out etc., they might want to have some cash, as they are likely not going to forgo eating etc... that said I would treat it as money to be used in place of a credit card (with the high rates) etc... Again I am not saying spend the money, I am being realistic, that it takes money to secure an apt, and unless you can borrow cheaper than 6% elsewhere (I know I could probably get unsecured money cheaper than that where I live, but I don't know the OPs situation). I wouldn't invest it given the situation personally. If you have a great job, it won't matter, you will build up past 1200 soon and can then start to invest a portion of that cash. If you don't, then you shouldn't be risking debt money, especially if your level of sophistication in the market has you here asking the question. That 6% savings is tax free as well, so you need to gross it up based on your tax situation. Also make note of any currency conversions that would need to happen, so depending on what you want to invest in, currency risk could be a real concern as well. One other reason I think getting down at least a portion of the debt could be good is simplification. Can't spend money you don't view yourself as having. Some people might be more disciplined to reign in spending when they see a lower number in their account. I'm personally not one of those people, but again, I would likely kill the debt off now just to have one less thing on my mind... but only as soon as I am stable (know where I am going to live, have enough to eat, and relatively sure that will continue in the future...)", "title": "" }, { "docid": "392980", "text": "\"Your plan as proposed will not work, because it goes against how banks make money. Banks make money in two ways: (1) Fees [including account fees, investment advice fees, mortgage application fees, etc.]; and (2) Interest Rate Spread. They borrow money for x%, and they lend it out for x+y%. In a simple form, someone gives the bank a deposit, and earns 1%. The bank turns around to the next person in line and loans the money to them for 4%. You are asking them to turn the interest rate spread into a cost instead of their main source of profit: You are asking the bank to borrow money from another person paying them 1.2% interest, and then loan the money to you, paying you 0.6% interest and keeping 0.6% for themselves. The bank would lose money doing this. Technically yes, you can borrow from a bank and invest it in something earning above the 4% interest they will charge you. You can then pay the bank's interest off of your earnings, and make some profit for yourself. BUT this carries an inherent risk: If your investment loses money, you still owe the bank, effectively increasing the negative impact of your investment. This tactic is called \"\"Leveraging\"\"; you can look it up on this site or on google. It is not something you should do if you do not fully understand the risks you are taking on. Given that you are asking this question, I would suggest tactfully that you are not yet well informed enough to make this sort of investment. You run serious risk of losing everything if you over-leverage (assuming the banks will even lend you money in the first place).\"", "title": "" }, { "docid": "587192", "text": "If you're under age 55 and in good health generally you cannot withdraw your funds from super and your super fund cannot provide you with any financial assistance eg lend you money. However, for a very small percentage of people with unrestricted non preserved superannuation components ( check your statement most people's superannuation is 'preserved'which means they cannot access it until they meet a 'condition of release')they may withdraw their super benefits upto the unrestricted non preserved amount. For healthy (& able) persons aged 55 and over they may access their super under the following conditions: I can understand your frustration of having your money compulsory tied up in superannuation especially given the poor investment returns of the past 5 years. However, superannuation may be more flexible than you realize, I am an adviser at Grant Thornton and I am constantly telling clients that superannuation is not an invest but it the most tax effective long term savings vehicle available to Australians for their investment savings eg max 15% tax on income and capital gains if held for a year are taxed at 10%. If you're not happy with your investment returns you may like to seek some advice or,set up your own super fund - a self managed super fund where you can invest a wide variety of assets; shares, managed funds,cash, term deposits, property( your super fund can even borrow to help acquire the property) I hope this helps", "title": "" }, { "docid": "219910", "text": "I was active in Prosper when it started up. It was very easy to get attracted to the high risk loans with big interest rates and I lost about 14% after all my loans ran their course. (There's 10 still active, but it won't change the figure by much). Prosper has wider standards than Lending club, so more borrowers with worse credit scores could ask for loans. Lenders could also set interest rates far lower, so they could end up having loans with rates lower than the risk implied. This was set up with the idea of a free market where anyone could ask to borrow and anyone could loan money at whatever interest rate they wanted, It turns out a lot of lenders were not as smart as they thought they were. (Aside: it's funny how people will clamor for a free market, but when they lose money will suddenly be against the free market they said they wanted, this seems to apply to both individual p2p lenders up to massive multinational banks.). Since then Prosper has tightened their standards on who can borrow and the interest rates are now fixed. So I expect going forward it will be less easy to lose a bunch of money. The key is that one bad loan will erase the return of many good ones. So it's best to examine the loans carefully and stick with the high quality. Simplified Example If you have 10 1 yr loans of $100 each paying 10% interest/year, you get 10% return at the end of the year, so $100 (10% of $1000.). BUT if one loan goes bad at the start, you have lost money. So a 90% success rate in picking borrowers leads to a loss. You want to diversity over quite a few loans and you want to fund quality loans. I think really enjoyed investing through Prosper, because it gave me an insight into lending and loss ratios that I had not had before. It also caused me to look at the banks with even more incredulity when the case of the no-doc loans and neg-am loans came to light.", "title": "" }, { "docid": "390359", "text": "\"I invested in Prosper.com loans. I'm getting out. I only have about $37 left, and as the principal is doled back to me, I withdraw the money. The default rate I experienced was over 30%. Only six of the 53 loans I invested in were with borrowers whose credit rating was less than \"\"A.\"\" Borrowers with a rating of \"\"A\"\" and \"\"AA\"\" had a higher proportion of defaults that those below \"\"A\"\". Some of my blogging colleagues were wise enough not to start this game. Some who invest in other P2P lending are almost certainly doing it with \"\"found money.\"\" They post articles with affiliate links. As people sign up, they get the commissions deposited in their accounts, which they invest. As they update their blogs with the returns on their portfolio, it serves to encourage more signups, and the machine continues on. Even if they lose money on the invested loans, they're still ahead. To paraphrase John Chow's tagline: They make money with Lending Club by telling people how much money they're making with Lending Club. It's almost like investing with the house's money. My high default rate might be because I started earlier in the game. Borrower screening and criteria have gotten tighter with time. I don't recommend investing in P2P loans. My experience has been that a large percentage of borrowers requesting loans on these sites have run out of options, which the credit reporting doesn't reflect accurately enough.\"", "title": "" }, { "docid": "457584", "text": "\"The reason that UltraLong funds and the like are bad isn't because of the leverage ratio. It's because they're compounded daily, and the product of all the doubled daily returns is not mathematically equivalent to the double the long-term return. I'd consider providing big fancy equations using uppercase pi as the 'product of elements in a sequence' operator and other calculus fanciness, but that would be overkill, I don't think I can do TeX here, and I don't know the relevant TeX anyway. Anyway. From the economics theory perspective, the ideal leverage ratio is 1X - that is, unlevered, straight investment. Consider: Using leverage costs money. You know that, surely. If someone could borrow money at N% and invest at an expected N+X%, where X > 0, then they would. They would borrow all the money they could and buy all the S&P500 they could. But when they bought all that S&P500, they'd eventually run out of people who were willing to sell it for that cheap. That would mean the excess return would be smaller. Eventually you'd get to a point where the excess return is... zero? .... well, no, empirically, we can see that it's definitely not zero, and that in the real world that stocks do return more than bonds. Why? Because stocks are riskier than bonds. The difference in expected return between an index like the S&P500 and a US Treasury bond is due to the relative riskiness of the S&P500, which isn't guaranteed by the US Government to return your principal. Any money that you make off of leverage comes from assuming some sort of a risk. Now, assuming risk can be a profitable thing to do, but there are also a lot of people out there with higher risk tolerance than you, like insurance companies and billionaires, so the market isn't exactly short of people willing to take risks, and you shouldn't expect the returns of \"\"assuming risk\"\" in the general case to be qualitatively awesome. Now, it's true that investing in an unlevered fashion is risky also. But that's not an excuse to go leveraged anyway; it's a reason to hold back. In fact, regular stocks are sufficiently risky that most people probably shouldn't be holding a 100% stock portfolio. They should be tempering that risk with bonds, instead, and increasing the size of their bond holdings over time. The appropriate time to use leverage is when you have information which limits your risk. You have done research, and have reason to believe that you understand the future of an individual stock/index better than the rest of the stock market does. You calculate that the potential for achieving returns with leverage outweighs the risks. Then you dump your money into the leveraged position. (In exchange for this, the market receives information about anticipated future returns of this instrument, because of the price movement which occurs as a result of someone putting his money where his mouth is.) If you're just looking to dump money into broad market indicies in a leveraged fashion, you're doing it wrong. There is no free money. (Ed. Which is not to say there's not money. There's lots of money. But if you go looking for the free kind, you won't find it, and may end up with money that you thought was free but was actually quite expensive.) Edit. Okay, so you don't like my answer. I'm not surprised. I'm giving you a real answer instead of a \"\"make free money\"\" answer. Okay. Here's your \"\"how to make free money\"\" answer. Assume you are using a constant leverage ratio over the length of time you've invested your money, and you don't get to just jump into and out of the market (that's market-timing, not leverage) so you have to stay invested. You're going to have a scenario which falls into one of these categories: The S&P500 historically rises over time. The average rate of return probably exceeds the average interest rate. So the ideal leverage ratio is infinite. Of course, this is a stupid answer in real life because you can't pull that off. Your risk tolerance is too low and you will have trouble finding a lender willing to lend you unsecured money, and you'll probably lose all your money in a crash sooner or later. Ultimately it's a stupid answer because you're asking the wrong question. You should probably ask a better question: \"\"when I use leverage to gain additional exposure to risk, am I being properly compensated for assuming that risk?\"\"\"", "title": "" }, { "docid": "329930", "text": "\"I would undoubtedly sell the investments if they are positive, maybe even a little negative. That's what non-retirement investments are for, building wealth to spend, give, etc. Flipping things may put it in perspective. Would you borrow money or liquidate your emergency fund in order to invest in mutual funds? If you can completely ignore risk then this MAY make sense. Let's say if you could borrow money at 3.75% and had a \"\"guaranteed\"\" investment return of 7.5% and a \"\"guaranteed\"\" source of income (job). But mutual funds (stocks, bonds) aren't even guaranteed to make money and they most definitely can lose and lose big. Also, I hope your job isn't in any way tied to the oil industry. On the other hand, if you take a loan and fall on hard times you can liquidate your mutual funds to get out of the bind, but you are at the mercy of the market and the worth of your investments at that point. So it may come down to whether you want to choose when to spend your investments, when they are up or at some future date when they may be worth much less (or much more).\"", "title": "" } ]
929	Patients with microcytosis and higher erythrocyte count were more resistant to severe malarial anaemia when infected with Plasmodium falciparum.	[ { "docid": "18174210", "text": "BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria. METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia. In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.", "title": "Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia" } ]	[ { "docid": "2460304", "text": "Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.", "title": "Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance." }, { "docid": "9254550", "text": "BACKGROUND & OBJECTIVES Anaemia is commonly observed in children with malaria, but reports on leucocyte and platelet count abnormalities associated with malaria are inconsistent. This study examined the effect of age, gender, parasite density and temperature on haematological parameters in children with acute uncomplicated malaria. METHODS Haematological parameters were determined in children with acute uncomplicated malaria, and these were correlated with age, sex, temperature and parasite density. Statistical analysis was done using SAS 9.1. RESULTS Six hundred and ninety five children with acute uncomplicated malaria participated in the study. The mean age was 51.7 months +/- 33.8. At presentation, anaemia occurred in 43.8% of the patients and children <5 yr had a significantly lower haematocrit (28.4% +/- 4.8) than that of older children (32.8% +/- 4.8) (p <0.001), but the haematocrit was not significantly different by days 14 and 28. There was no difference between both sexes. Leucocytosis was more frequently seen than leucopenia (9.5% vs 3%). Thrombocytopenia was found in 59.3% of enrolled patients. More than half of the patients with thrombocytopenia had recovered by Day 28. Baseline platelet count was related to Day 14 (r = 0.6, p < 0.0001) and Day 28 (r = 0.2, p = 0.0015) and the haematocrit on Day 28 (r = 0.12, p = 0.00197). Platelet count showed no correlation with temperature, parasite density and leucocyte count. Haematocrit correlated with age (r = 0.4, p < 0.0001); but not with parasite density or temperature. Leucocyte count showed no correlation with age or parasite density. CONCLUSION While thrombocytopenia was the most common haematological finding and may be of diagnostic importance, anaemia and leucocytosis were more common in the under fives.", "title": "Age as a risk factor for thrombocytopenia and anaemia in children treated for acute uncomplicated falciparum malaria." }, { "docid": "25420421", "text": "Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.", "title": "Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome." }, { "docid": "25938221", "text": "A specific retinopathy has been described in African children with cerebral malaria, but in adults this has not been extensively studied. Since the structure and function of the retinal vasculature greatly resembles the cerebral vasculature, study of retinal changes can reveal insights into the pathophysiology of cerebral malaria. A detailed observational study of malarial retinopathy in Bangladeshi adults was performed using high-definition portable retinal photography. Retinopathy was present in 17/27 adults (63%) with severe malaria and 14/20 adults (70%) with cerebral malaria. Moderate or severe retinopathy was more frequent in cerebral malaria (11/20, 55%) than in uncomplicated malaria (3/15, 20%; P=0.039), bacterial sepsis (0/5, 0%; P=0.038) or healthy controls (0/18, 0%; P<0.001). The spectrum of malarial retinopathy was similar to that previously described in African children, but no vessel discolouration was observed. The severity of retinal whitening correlated with admission venous plasma lactate (P=0.046), suggesting that retinal ischaemia represents systemic ischaemia. In conclusion, retinal changes related to microvascular obstruction were common in adults with severe falciparum malaria and correlated with disease severity and coma, suggesting that a compromised microcirculation has important pathophysiological significance in severe and cerebral malaria. Portable retinal photography has potential as a valuable tool to study malarial retinopathy.", "title": "The spectrum of retinopathy in adults with Plasmodium falciparum malaria" }, { "docid": "17168045", "text": "BACKGROUND This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging. METHODS The microcirculation in the rectal mucosa of adult patients with severe malaria was assessed by use of OPS imaging, at admission and then daily. Comparison groups comprised patients with uncomplicated falciparum malaria, patients with bacterial sepsis, and healthy individuals. RESULTS Erythrocyte velocities were measured directly in 43 adult patients with severe falciparum malaria, of whom 20 died. Microcirculatory blood flow was markedly disturbed, with heterogeneous obstruction that was proportional to severity of disease. Blocked capillaries were found in 29 patients (67%) and were associated with concurrent hyperdynamic blood flow (erythrocyte velocity, >750 mm/s) in adjacent vessels in 27 patients (93%). The proportion of blocked capillaries correlated with the base deficit in plasma and with the concentration of lactate. Abnormalities disappeared when the patients recovered. In healthy individuals and in patients with uncomplicated malaria or sepsis, no stagnant erythrocytes were detected, and, in patients with sepsis, hyperdynamic blood flow was prominent. CONCLUSION Patients with severe falciparum malaria show extensive microvascular obstruction that is proportional to the severity of the disease. This finding underscores the prominent role that microvascular obstruction plays in the pathophysiology of severe malaria and illustrates the fundamental difference between the microvascular pathophysiology of malaria and that of bacterial sepsis.", "title": "Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria." }, { "docid": "3929361", "text": "BACKGROUND Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. METHOD AND FINDINGS A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. CONCLUSIONS The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination.", "title": "Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance" }, { "docid": "13959707", "text": "BACKGROUND Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) = 2.7 (95% CI 1.42, 5.01, P = 0.002) but not in those without detectable parasitaemia (HR = 1.0 (95% CI 0.74, 1.42, P = 0.9). CONCLUSIONS We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.", "title": "The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children" }, { "docid": "40900567", "text": "The multiplication rates and invasiveness of Plasmodium falciparum parasites isolated from adult Thai patients hospitalized with uncomplicated malaria (n=34) were compared with those from persons with severe malaria (n=42). To simulate severe malaria and control for host effects, the in vitro cultures were adjusted to 1% parasitemia and used the same red blood cell donor. P. falciparum isolates from persons with severe malaria had initial cycle multiplication rates in vitro that were 3-fold higher than those from uncomplicated malaria (median [95% confidence interval], 8.3 [7. 1-10.5] vs. 2.8 [1.7-3.9]; P=.001). Parasites causing severe malaria exhibited unrestricted red blood cell invasion, whereas those from uncomplicated malaria were restricted to a geometric mean of 40 (31%-53%) of red blood cells. P. falciparum parasites causing severe malaria were less selective and multiplied more at high parasitemias than those causing uncomplicated malaria.", "title": "Parasite multiplication potential and the severity of Falciparum malaria." }, { "docid": "17925632", "text": "We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg (base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria (95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.", "title": "Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria." }, { "docid": "27889071", "text": "The high prevalence of microcytosis (defined here as mean cell haemoglobin<27 pg) with no other abnormality is a principal cause of confusion in screening for haemoglobin disorders. Here we report the results of a small pilot study aiming to resolve this confusion by routinely proceeding to plasma ferritin and HPLC assay, using the original sequestrene blood sample, when microcytosis is detected. Participants comprised a random sample of 1,302 people referred for a full blood count by their General Practitioner (GP) to the laboratory of a North London district general hospital serving a multi-ethnic inner-city population. Ethnicity was established by questionnaire. In North Europeans, microcytosis was present in 3% of males (half were iron-deficient) and 11% of females (most were iron-deficient). Among ethnic minorities, microcytosis was present in 35% of males (one tenth were iron-deficient), and 45% of females (less than half were iron-deficient): an exclusion diagnosis of \"probable alpha thalassaemia\" could be made in the remainder. We conclude that when microcytosis is present, routine further analysis of the original sequestrene sample by plasma ferritin assay and haemoglobinopathy screening could lead to a more efficient and cost-effective laboratory service for primary care and maternity services.", "title": "Microcytosis, iron deficiency and thalassaemia in a multi-ethnic community: a pilot study." }, { "docid": "42373943", "text": "BACKGROUND Malaria is considered as the main differential diagnosis of acute febrile illness in the tropics, and alteration of various hematological parameters has been observed in patients with malaria. AIM To ascertain if certain hematological parameters increase the probability of malaria in patients with acute febrile illnesses. SETTINGS AND DESIGN Hospital based, prospective cohort study. METHODS AND MATERIAL All consecutive in patients with fever of less than seven days in duration were included in the study. Patients where localizing cause for fever could be determined were excluded. Hematological parameters (Hemoglobin, Red cell distribution width (RDW), Leukocyte count, and platelet counts) were determined by using automated counter, and peripheral smear examination for malarial parasite was taken as gold standard for the diagnosis of malaria. STATISTICAL ANALYSIS USED Diagnostic accuracy was measured by computing sensitivity, specificity, predictive values and likelihood ratios. The precision of these estimates was evaluated using 95% confidence intervals. RESULTS AND CONCLUSIONS A total of 184 patients were included in the study and 70 (38%) had a positive peripheral smear for malarial parasite. Thrombocytopenia alone (platelet countless than 150,000/mm3) was a predictor for malaria (Sn 60%, Sp 88%, LR+ 5.04) and in combination with anemia (Hb < 10 g/dl) it was next best parameter (Sn 69%, Sp 74%, LR+ 2.77). RDW and leukocyte count were not predictive. The conclusion of this study is that the presence of thrombocytopenia in a patient with acute febrile illness increases the probability of malarial infection.", "title": "Can hematological parameters discriminate malaria from nonmalarious acute febrile illness in the tropics?" }, { "docid": "1805641", "text": "BACKGROUND Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas. METHODS AND FINDINGS We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting. CONCLUSIONS Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.", "title": "Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity" }, { "docid": "6503185", "text": "Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.", "title": "Malaria biology and disease pathogenesis: insights for new treatments" }, { "docid": "20761364", "text": "Artemisinins are peroxidic antimalarial drugs known to be very potent but highly chemically unstable; they degrade in the presence of ferrous iron, Fe(II)-heme, or biological reductants. Less documented is how this translates into chemical stability and antimalarial activity across a range of conditions applying to in vitro testing and clinical situations. Dihydroartemisinin (DHA) is studied here because it is an antimalarial drug on its own and the main metabolite of other artemisinins. The behaviors of DHA in phosphate-buffered saline, plasma, or erythrocyte lysate at different temperatures and pH ranges were examined. The antimalarial activity of the residual drug was evaluated using the chemosensitivity assay on Plasmodium falciparum, and the extent of decomposition of DHA was established through use of high-performance liquid chromatography with electrochemical detection analysis. The role of the Fe(II)-heme was investigated by blocking its reactivity using carbon monoxide (CO). A significant reduction in the antimalarial activity of DHA was seen after incubation in plasma and to a lesser extent in erythrocyte lysate. Activity was reduced by half after 3 h and almost completely abolished after 24 h. Serum-enriched media also affected DHA activity. Effects were temperature and pH dependent and paralleled the increased rate of decomposition of DHA from pH 7 upwards and in plasma. These results suggest that particular care should be taken in conducting and interpreting in vitro studies, prone as their results are to experimental and drug storage conditions. Disorders such as fever, hemolysis, or acidosis associated with malaria severity may contribute to artemisinin instability and reduce their clinical efficacy.", "title": "Stability of the antimalarial drug dihydroartemisinin under physiologically relevant conditions: implications for clinical treatment and pharmacokinetic and in vitro assays." }, { "docid": "2264455", "text": "There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.", "title": "Vaccines against malaria" }, { "docid": "37205685", "text": "Malaria resistant to chloroquine has now been confirmed in more than 40 countries. The drug was introduced in 1934, but was not in large-scale use until the early 1950s. Anecdotal reports suggest that resistance emerged as early as 1957 both in Colombia and along the then Cambodia-Thailand border area. But by 1960, resistance in these areas was confirmed - and may represent two separate events. Resistance spread rapidly, with a new focus of resistance confirmed in East Africa by 1977. Chloroquine resistance represents a severe problem both for prophylaxis and treatment of malaria. In this aricle, David Payne traces the spread of resistance and discusses some of its implications.", "title": "Spread of chloroquine resistance in Plasmodium falciparum." }, { "docid": "12409683", "text": "BACKGROUND Artemisinin combination therapies (ACT), which are increasingly being introduced for treatment of Plasmodium falciparum malaria, are more effective against sexual stage parasites (gametocytes) than previous first-line antimalarials and therefore have the potential to reduce parasite transmission. The size of this effect is estimated in symptomatic P. falciparum infections. METHODS Data on 3,174 patients were pooled from six antimalarial trials conducted in The Gambia and Kenya. Multivariable regression was used to investigate the role of ACT versus non-artemisinin antimalarial treatment, treatment failure, presence of pre-treatment gametocytes and submicroscopic gametocytaemia on transmission to mosquitoes and the area under the curve (AUC) of gametocyte density during the 28 days of follow up. RESULTS ACT treatment was associated with a significant reduction in the probability of being gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26), transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means 0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the difference between ACT and non-artemisinin impact. The presence of slide-positive gametocytaemia prior to treatment significantly reduced ACT impact on gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia reduced estimates of ACT impact in a high transmission setting in Kenya, but not in a lower transmission setting in the Gambia. CONCLUSION Treatment with ACT significantly reduces infectiousness of individual patients with uncomplicated falciparum malaria compared to previous first line treatments. Rapid treatment of cases before gametocytaemia is well developed may enhance the impact of ACT on transmission.", "title": "Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials" }, { "docid": "4336849", "text": "CHLOROQUINE is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function14. Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles5. The discovery that verapamil partially reverses chloroquine resistance in vitro 6 led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant (mdr) tumor cell lines. Indeed, Plasmodium falciparum contains at least two mdr-like genes7,8, one of which has been suggested to confer the chloroquine resistant (CQR) phenotype7,9,10. To determine if either of these genes is linked to chloroquine resistance, we performed a genetic cross between CQR and chloroquine-susceptible (CQS) clones of P. falciparum. Examination of 16 independent recombinant progeny indicated that the rapid efflux phenotype is controlled by a single gene or a closely linked group of genes. But, there was no linkage between the rapid efflux, CQR phenotype and either of the mdr-like P. falciparum genes or amplification of those genes. These data indicate that the genetic locus governing chloroquine efflux and resistance is independent of the known mdr-like genes.", "title": "Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross" }, { "docid": "8373753", "text": "The seasonal dynamics and spatial distributions of Anopheles mosquitoes and Plasmodium falciparum parasites were studied for one year at 30 villages in Malindi, Kilifi, and Kwale Districts along the coast of Kenya. Anopheline mosquitoes were sampled inside houses at each site once every two months and malaria parasite prevalence in local school children was determined at the end of the entomologic survey. A total of 5,476 Anopheles gambiae s.l. and 3,461 An. funestus were collected. Species in the An. gambiae complex, identified by a polymerase chain reaction, included 81.9% An. gambiae s.s., 12.8% An. arabiensis, and 5.3% An. merus. Anopheles gambiae s.s. contributed most to the transmission of P. falciparum along the coast as a whole, while An. funestus accounted for more than 50% of all transmission in Kwale District. Large spatial heterogeneity of transmission intensity (< 1 up to 120 infective bites per person per year) resulted in correspondingly large and significantly related variations in parasite prevalence (range = 38-83%). Thirty-two percent of the sites (7 of 22 sites) with malaria prevalences ranging from 38% to 70% had annual entomologic inoculation rates (EIR) less than five infective bites per person per year. Anopheles gambiae s.l. and An. funestus densities in Kwale were not significantly influenced by rainfall. However, both were positively correlated with rainfall one and three months previously in Malindi and Kilifi Districts, respectively. These unexpected variations in the relationship between mosquito populations and rainfall suggest environmental heterogeneity in the predominant aquatic habitats in each district. One important conclusion is that the highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys. The field-based estimate of entomologic parameters on a district level does not provide a sensitive indicator of transmission intensity in this study.", "title": "Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast." }, { "docid": "10617916", "text": "Background. Artemisinin-based combination therapy (ACT) reduces microscopically confirmed gametocytemia and mosquito infection. However, molecular techniques have recently revealed high prevalences of submicroscopic gametocytemia. Our objective here was to determine the effect of sulfadoxine-pyrimethamine (SP) monotherapy and treatment with SP plus amodiaquine (AQ), SP plus artesunate (AS), and artemether-lumefantrine (AL; Coartem) on submicroscopic gametocytemia and infectiousness. Methods. Kenyan children (n=528) 6 months-10 years of age were randomized to 4 treatment arms. Gametocytemia was determined by both microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. Results. Gametocyte prevalence, as determined by Pfs25 QT-NASBA, was 89.4% (219/245) at enrollment and decreased after treatment with SP plus AS, SP plus AQ, and AL. Membrane-feeding assays for a group of randomly selected children revealed that the proportion of infectious children was as much as 4-fold higher than expected when based on microscopy. ACT did not significantly reduce the proportion of infectious children but did reduce the proportion of infected mosquitoes. Conclusions. Submicroscopic gametocytemia is common after treatment and contributes considerably to mosquito infection. Our findings should be interpreted in the context of transmission intensity, but the effect of ACT on malaria transmission appears to be moderate and restricted to the duration of gametocyte carriage and the proportion of mosquitoes that are infected by carriers.", "title": "Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum." }, { "docid": "25069745", "text": "OBJECTIVE To describe the epidemiology of urban malaria, an emerging problem in sub-Saharan Africa. METHOD Cross-sectional surveys of communities in Accra and Kumasi, Ghana, determining risk factors for malaria infection and anaemia in children aged 6-60 months. RESULTS Malaria prevalence rates ranged from 2% to 33% between urban communities. 47.1% of children were anaemic (Hb<11.0 g/dl). Factors associated with malaria prevalence were low socio-economic status, age and anaemia. The attributable risks of anaemia and severe anaemia (Hb<8.0 g/dl) caused by malaria were 5% and 23% respectively. CONCLUSIONS Malaria in urban areas displayed a heterogeneity and complexity that differed from the rural environment, which has important implications for malaria control. Marked intra-city variation indicates the importance of targeting specific areas or districts. The most vulnerable group, the urban poor, should be prioritized when designing control measures. This would require careful assessment of the malaria risk pattern in any city to guide an integrated control program.", "title": "Urban malaria and anaemia in children: a cross-sectional survey in two cities of Ghana." }, { "docid": "14806256", "text": "CONTEXT Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus. OBJECTIVES To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development. DESIGN Prospective cohort study. SETTING University-based urban HIV clinic. PATIENTS A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively. MAIN OUTCOME MEASURE Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy. RESULTS Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9% -44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %). Although chronicviral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 x 10(9)/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity. CONCLUSIONS Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus.", "title": "Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection." }, { "docid": "18344910", "text": "Objectives. To evaluate the predictive value of thrombocytopenia in malaria. Patients and Methods. It was a prospective observational study on all febrile patients with thrombocytopenia presenting to the Medical Unit of Hayat Abad Medical Complex during November 2008 to November 2010. Results. Of the total of 228 patients with fever and thrombocytopenia, 121 patients (53%) proved to be suffering from malaria. Of them 82 patients (68%) had falciparum malaria while 39 patients (32%) had vivax infection. Of these 121 patients, platelet counts ranged between 25,000 and 150,000/dL with a mean value of 101,000/dL (SD ± 47, 500) and a median of 75,000/dL. Of the 107 patients who were not suffering from malaria, the counts ranged between 10,000 and 150,000/dL with a mean value of 58,000/dL (SD ± 54, 000) and median of 50,000/dL. Conclusions. The presence of thrombocytopenia may be a predictor of malaria in adult population.", "title": "Thrombocytopenia as an Indicator of Malaria in Adult Population" }, { "docid": "45218443", "text": "The hemoglobinopathies are probably the world's most common genetic diseases: The World Health Organization has estimated that at least 5% of the population are carriers for one or other of the most serious forms, the alpha- and beta-thalassemias and the structural variant hemoglobins S, C, and E, which are found at polymorphic frequencies in many countries. All these hemoglobinopathies are believed to provide protection against malaria, and it is thought that, in malarial regions of the world, natural selection has been responsible for elevating and maintaining their gene frequencies, an idea first proposed 50 years ago by J.B.S. Haldane. Epidemiological studies undertaken in the 1950s on hemoglobin S in Africa provided support for the \"malaria hypothesis,\" but until recently it has proved extremely difficult to verify it for the thalassemias. The application of molecular methods has, however, provided new opportunities to address this old question. Population and molecular genetic analysis of thalassemia variants, and microepidemiological studies of the relationship between alpha-thalassemia and malaria in the southwest Pacific, have provided unequivocal evidence for protection. Surprisingly, some of this protection appears to derive from enhanced susceptibility in very young thalassemic children to both Plasmodium falciparum and, especially, P. vivax, and this early exposure appears to provide the basis for better protection in later life.", "title": "Thalassemia and malaria: new insights into an old problem." }, { "docid": "17077004", "text": "OBJECTIVES To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART). DESIGN Prospective cohort study of adults with HIV (Swiss HIV cohort study). SETTING Seven outpatient clinics throughout Switzerland. PARTICIPANTS The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years). MAIN OUTCOME MEASURES Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound. RESULTS During follow up 2985 (80%) participants reported a stable partnership on at least one occasion. When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership. In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without. Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/microl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression. CONCLUSIONS A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.", "title": "Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study." }, { "docid": "17433284", "text": "BACKGROUND According to willingness of the Ministry of Health, Iran and presence of appropriate conditions for disease elimination, national malaria control program decided to conduct a research to clarify malaria status in 2007 and to provide required information to perform the elimination program. This review is comprised of the basis of national malaria elimination program in vision of 2025, which was started in 2010. METHODS In this descriptive study, data were analyzed by applications of different variables at district level. All districts in the three south eastern provinces, in which malaria has local transmission, were considered. Malaria cases has been determined and studied based on the national malaria surveillance system. RESULTS Since vivax malaria is predominant in Sistan & Baluchestan Province, number of vivax cases is equal to malaria positive cases approximately. The important point is that Nikshahr contains the maximum number of local vivax cases in this province and the maximum number of falciparum cases is reported from Sarbaz district. Among all districts of Hormozgan Province, no case of autochthonous falciparum was detected except in Bandar Jask and one case in Minab. There was no case of autochthonous falciparum in Kerman Province, except in Kahnoj and Ghale Ganj that each of them had one case in 2007. CONCLUSION It appears that the report of locally transmitted cases in Iran is increasing over the past few years, before starting malaria elimination plan. Since the Afghan refugees started to return to their own country so the main source of reporting of imported malaria cases reduced and local cases would be demonstrated more clearly.", "title": "Determination of Malaria Epidemiological Status in Iran’s Malarious Areas as Baseline Information for Implementation of Malaria Elimination Program in Iran" }, { "docid": "21479231", "text": "RATIONALE The outcome of fully intermittent thrice-weekly antituberculosis treatment of various durations in HIV-associated tuberculosis is unclear. OBJECTIVES To compare the efficacy of an intermittent 6-month regimen (Reg6M: 2EHRZ(3)/4HR(3) [ethambutol, 1,200 mg; isoniazid, 600 mg; rifampicin, 450 or 600 mg depending on body weight <60 or > or =60 kg; and pyrazinamide, 1,500 mg for 2 mo; followed by 4 mo of isoniazid and rifampicin at the same doses]) versus a 9-month regimen (Reg9M: 2EHRZ(3)/7HR(3)) in HIV/tuberculosis (TB). METHODS HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were randomly assigned to Reg6M (n = 167) or Reg9M (n = 160) and monitored by determination of clinical, immunological, and bacteriological parameters for 36 months. Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up, whereas the secondary outcome was death. Intent-to-treat and on-treatment analyses were performed. All patients were antiretroviral treatment-naive during treatment. MEASUREMENTS AND MAIN RESULTS Of the patients, 70% had culture-positive pulmonary TB; the median viral load was 155,000 copies/ml and the CD4(+) cell count was 160 cells/mm(3). Favorable response to antituberculosis treatment was similar by intent to treat (Reg6M, 83% and Reg9M, 76%; P = not significant). Bacteriological recurrences occurred significantly more often in Reg6M than in Reg9M (15 vs. 7%; P < 0.05) although overall recurrences were not significantly different (Reg6M, 19% vs. Reg9M, 13%). By 36 months, 36% of patients undergoing Reg6M and 35% undergoing Reg9M had died, with no significant difference between regimens. All 19 patients who failed treatment developed acquired rifamycin resistance (ARR), the main risk factor being baseline isoniazid resistance. CONCLUSIONS Among antiretroviral treatment-naive HIV-infected patients with TB, a 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen. ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment. Clinical Trials Registry Information: ID# NCT00376012 registered at www.clinicaltrials.gov.", "title": "Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial." }, { "docid": "1173667", "text": "Experience gained from the Global Malaria Eradication Program (1955-72) identified a set of shared technical and operational factors that enabled some countries to successfully eliminate malaria. Spatial data for these factors were assembled for all malaria-endemic countries and combined to provide an objective, relative ranking of countries by technical, operational, and combined elimination feasibility. The analysis was done separately for Plasmodium falciparum and Plasmodium vivax, and the limitations of the approach were discussed. The relative rankings suggested that malaria elimination would be most feasible in countries in the Americas and Asia, and least feasible in countries in central and west Africa. The results differed when feasibility was measured by technical or operational factors, highlighting the different types of challenge faced by each country. The results are not intended to be prescriptive, predictive, or to provide absolute assessments of feasibility, but they do show that spatial information is available to facilitate evidence-based assessments of the relative feasibility of malaria elimination by country that can be rapidly updated.", "title": "Ranking of elimination feasibility between malaria-endemic countries" }, { "docid": "2526777", "text": "Falciparum malaria kills, and it particularly kills the rural poor. Artemisinin derivatives, such as artesunate, are a vital component of Plasmodium falciparum malaria treatment and control in the face of globally increasing antimalarial drug resistance. Since 1998 a worsening epidemic of sophisticated counterfeit “artesunate” tablets (containing no artesunate) has plagued mainland Southeast Asia (see Figure S1). In some countries, most of the available artesunate is fake [ 1–5]. Artemisinin derivatives are remarkably rapid in their antimalarial effects, and they are very well tolerated. So where these medicines are available, they are sought after. But as they are relatively expensive, a demand is created for cheaper versions amongst the poorest and most vulnerable people, upon whom the counterfeiters have preyed–with fatal results.", "title": "Manslaughter by Fake Artesunate in Asia—Will Africa Be Next?" }, { "docid": "28806780", "text": "Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.", "title": "Poverty, Hunger, Education, and Residential Status Impact Survival in HIV" } ]
5a8810d65542997e5c09a591	Which Opera has more acts Nabucco or Mitridate, re di Ponto ?	[ { "docid": "4435955", "text": "Mitridate, re di Ponto (\"Mithridates, King of Pontus\"), K. 87 (74a), is an early opera seria in three acts by Wolfgang Amadeus Mozart. The libretto is by after Giuseppe Parini's Italian translation of Jean Racine's play \"Mithridate\".", "title": "" }, { "docid": "1192212", "text": "Nabucco (] ; short for Nabucodonosor ] ~] , English Nebuchadnezzar) is an Italian-language opera in four acts composed in 1841 by Giuseppe Verdi to an Italian libretto by Temistocle Solera. The libretto is based on biblical books of Jeremiah and Daniel and the 1836 play by Auguste Anicet-Bourgeois and Francis Cornue, although Antonio Cortese's ballet adaptation of the play (with its necessary simplifications), given at La Scala in 1836, was a more important source for Solera than the play itself. Under its original name of \"Nabucodonosor\", the opera was first performed at La Scala in Milan on 9 March 1842.", "title": "" } ]	[ { "docid": "21264645", "text": "The Teatro Regio Ducal (Italian, \"Royal Ducal Theatre\") was the opera house in Milan from 26 December 1717 until 25 February 1776, when it was burned down following a carnival gala. Many famous composers and their operas are associated with it, including the premieres of Mozart's \"Ascanio in Alba\", \"Mitridate, re di Ponto\", and \"Lucio Silla\". The opera house also saw the premiere of Maria Teresa Agnesi Pinottini's \"Ciro in Armenia\" in 1753; one of the earliest successfully received operas by a female composer. Variant forms such as \"Regio-Ducal Teatro\" and \"Teatro Regio Ducale\" are also seen.", "title": "" }, { "docid": "18602481", "text": "Il Mitridate Eupatore (\"Mithridates Eupator\") is an opera seria in five acts by the Italian composer Alessandro Scarlatti with a libretto by Girolamo Frigimelica Roberti. It was first performed at the Teatro San Giovanni Grisostomo, Venice on 5 January, 1707. A failure at its premiere, \"Mitridate Eupatore\" is now considered one of the finest of Scarlatti's operas.", "title": "" }, { "docid": "40584928", "text": "David Serero (born 22 April 1981) is a French baritone opera singer, actor, producer and philanthropist. He has played more than 1,000 concerts worldwide, and has performed lead roles in opera, theater and musicals such as Shylock (\"Merchant of Venice\"), Othello (\"Othello\"), Nabucco (\"Nabucco\"), Don Quixote (\"Man of La Mancha\"), Escamillo (\"Carmen\"), Enrico (\"Lucia di Lammermoor\"), Amonasro (\"Aida\"), the title roles of Don Giovanni and Rigoletto and starred in more than 100 films and TV series. In 2017, David Serero is honored in the Who's Who America for outstanding achievement in the entertainment world and for his contribution for the betterment of contemporary society.", "title": "" }, { "docid": "19078719", "text": "Arsilda, regina di Ponto is a dramma per musica by Antonio Vivaldi. The opera was first performed at the Teatro Sant'Angelo in Venice on 27 or 28 October 1716.", "title": "" }, { "docid": "55303000", "text": "Mitridate is an opera by Nicola Antonio Porpora to a libretto by Filippo Vanstriper premiered in Rome in 1730. Porpora and revived and revised the work for London (1736) with actor-manager and librettist Colley Cibber in direct competition with Handel's opera house. The London version of the opera will be performed for the 250th anniversary of Porpora's death at the Schwetzingen Festival in November 2017.", "title": "" }, { "docid": "37762026", "text": "Christian Van Horn (born 1978 in Rockville Centre, New York) is an American operatic bass-baritone and has appeared with many of the world's most prestigious opera companies, including San Francisco Opera, The Metropolitan Opera, Lyric Opera of Chicago, Bayerische Staatsoper, Teatro dell'Opera di Roma, Netherlands Opera, Salzburg Festival, Los Angeles Opera, The Grand Théâtre du Genève, and Canadian Opera Company. His roles include the title role in Le nozze di Figaro, the Four Villains in Les Contes d'Hoffmann, Mephistopheles in Faust, Zaccaria in Nabucco, Escamillo in Carmen, Raimondo in Lucia di Lammermoor, Banquo in Macbeth, Colline in La Bohème, and Claudio in Aggrippina. Van Horn has also appeared as a concert soloist with the Berlin Philharmonic, Chicago Symphony Orchestra, San Francisco Symphony. Melbourne Symphony Orchestra, and the Los Angeles Philharmonic among others.", "title": "" }, { "docid": "51581800", "text": "Artaserse is an opera (\"dramma per musica\") in three acts composed by Johann Adolph Hasse to an Italian libretto adapted from that by Metastasio by Giovanni Boldini. It premiered at the Teatro di San Giovanni Grisostomo in Venice on 11 February 1730, shortly after the libretto's first setting by Leonardo Vinci premiered in Rome 6 days earlier. Metastasio's libretto, \"Artaserse\", has been used in more than 90 works. Hasse himself would later re-work the score for performances at the Opernhaus am Zwinger in Dresden (1740) and the Teatro di San Carlo in Naples (1760).", "title": "" }, { "docid": "9613655", "text": "Norine Burgess is a Canadian singer. She is a graduate of the University of Calgary and the University of Toronto’s Opera School, mezzo-soprano. She received additional training as a member of the Canadian Opera Company (COC) Ensemble where she appeared in Electra, Suor Angelica, Lulu and Der Rosenkavalier. Ms. Burgess also performed Le Nozze di Figaro(Cherubino), Ariadne auf Naxos (Dryad), La Traviata(Flora) and Die Zauberflöte (Second Lady) with the COC. Additional operatic successes include Le Nozze di Figaro (Cherubino) and Carmen (Mercedes) with the Vancouver Opera, Fenena in Nabucco with Manitoba Opera, Albert Herring (Nancy) with the Calgary Opera and many appearances with the Edmonton Opera.", "title": "" }, { "docid": "1944828", "text": "Giovanna d'Arco (\"Joan of Arc\") is an operatic \"dramma lirico\" with a prologue and three acts by Giuseppe Verdi set to an Italian libretto by Temistocle Solera, who had prepared the libretti for both \"Nabucco\" and \"I Lombardi\". It is Verdi's seventh opera.", "title": "" }, { "docid": "31256016", "text": "Seleuco, re di Siria (\"Seleucus, King of Syria\") is an \"opera seria\" in three acts by Francesco Bianchi. The libretto was by Mattia Botturini, after \"Antioco\" by Apostolo Zeno and Pietro Pariati, a libretto first set by Francesco Gasparini in 1705.", "title": "" }, { "docid": "28151809", "text": "Siroe is a dramma per musica or opera seria in 3 Acts by composer Pasquale Errichelli. The opera uses an Italian language libretto by Pietro Metastasio. The opera premiered at the Teatro di San Carlo in Naples on 26 December 1758. Vincenzo Re designed the sets for the premiere production.", "title": "" }, { "docid": "6781304", "text": "\"Va, pensiero \" (] ), also known in English as the \"Chorus of the Hebrew Slaves\", is a chorus from the third act of the opera \"Nabucco\" (1842) by Giuseppe Verdi, with a libretto by Temistocle Solera, inspired by Psalm 137. It recollects the period of Babylonian captivity after the loss of the First Temple in Jerusalem in c. 500 BCE. The opera with its powerful chorus established Verdi as a major composer in 19th-century Italy. The full incipit is \"Va, pensiero, sull'ali dorate\", meaning \"Go, thought, on golden wings\".", "title": "" }, { "docid": "6793778", "text": "\"Di quella pira \" is a short tenor aria (or more specifically, a cabaletta) sung by Manrico in act 3, scene 2, of Giuseppe Verdi's opera \"Il trovatore\". It is the last number of the act.", "title": "" }, { "docid": "27248431", "text": "Nigel Levings is an Australian stage lighting designer. He has designed lights for over 400 productions. He works extensively on operas, and has designed a large portion of Opera Australia's repertoire. Some of his most significant works include operas such as \"The Demon\" at the Bregenz Festival and for Zurich Opera; \"Billy Budd\" for the Welsh National Opera, Opera Australia, Canadian Opera Company, and for the English National Opera; \"Nabucco\" for Opera Australia; \"Wozzeck\" for Opera Australia; \"L'Orfeo\" for Innsbrucker Festwochen der Alten Musik and the Berlin State Opera; \"A Midsummer Night's Dream\" for the 1994 Edinburgh Festival; \"La Belle Vivette\" for the English National Opera; \"Simon Boccanegra\" for the Royal Opera House, Washington National Opera, and Dallas Opera; \"Falstaff\" for Théâtre du Châtelet; \"Idomeneo\", \"Turandot\", and \"The Barber of Seville\" for the Houston Grand Opera; and \"Queen of Spades\" for the Dallas Opera.", "title": "" }, { "docid": "39014617", "text": "Caritea, regina di Spagna, ossia La morte di Don Alfonso re di Portogallo (\"Caritea, Queen of Spain, or, The Death of Don Alfonso, King of Portugal\"), is an opera in two acts by Saverio Mercadante, with a libretto by Paolo Pola. It was premiered at Teatro La Fenice in Venice on 21 February 1826.", "title": "" }, { "docid": "113319", "text": "Lulu (composed from 1929–1935, premièred incomplete in 1937 and complete in 1979) is an opera in three acts by Alban Berg. The German-language libretto was adapted by Berg himself from Frank Wedekind's two \"Lulu\" plays, \"Erdgeist\" (\"Earth Spirit\", 1895) and \"Die Büchse der Pandora\" (\"Pandora's Box\", 1904). Berg died before completing the third and final act, and in the following decades, the opera was typically performed incomplete. Since its publication in 1979, however, the Friedrich Cerha orchestration has become popular. Theodor W. Adorno wrote \"The opera \"Lulu\" is one of those works that reveals the extent of its quality the longer and more deeply one immerses oneself in it.\"", "title": "" }, { "docid": "8374179", "text": "Adelaide di Borgogna, ossia Ottone, re d'Italia (Adelaide of Burgundy, or Otto, King of Italy) is a two-act opera composed by Gioachino Rossini (with contributions by Michele Carafa) to a libretto by Giovanni Schmidt. It was premièred at the Teatro Argentina in Rome on 27 December 1817.", "title": "" }, { "docid": "27743157", "text": "Maria Christova is a Russian soprano. She won the Toulouse International Singing Competition in 1961. In 1970, she was a member of the company of the Royal Flemish Opera, performing in Nabucco and The Magic Flute. She has recorded for Nonesuch Records and Terpsichore.", "title": "" }, { "docid": "22348", "text": "Opera (] ; English plural: \"operas\"; Italian plural: \"opere\" ] ) is an art form in which singers and musicians perform a dramatic work combining text (libretto) and musical score, usually in a theatrical setting. In traditional opera, singers do two types of singing: recitative, a speech-inflected style and arias, a more melodic style, in which notes are sung in a sustained fashion. Opera incorporates many of the elements of spoken theatre, such as acting, scenery, and costumes and sometimes includes dance. The performance is typically given in an opera house, accompanied by an orchestra or smaller musical ensemble, which since the early 19th century has been led by a conductor.", "title": "" }, { "docid": "13617705", "text": "Statira principessa di Persia (\"Stateira, Princess of Persia\") is an opera - more specifically, a dramma per musica - in a prologue and three acts by Francesco Cavalli, set to a libretto by Giovanni Francesco Busenello. The opera was first performed in Venice at the Teatro SS. Giovanni e Paolo, on 18 January 1656.", "title": "" }, { "docid": "44939653", "text": "Re Enzo (\"King Enzo\") is an opera in three acts by Ottorino Respighi to a libretto by Alberto Donini (a student friend of Respighi). \"Re Enzo\" premiered on 12 March 1905 at the Teatro del Corso in Bologna. The singers were amateurs selected in the world of the Bolognese students; among them, Rosina Giovannoni Zacchi as Lauretta and Ernesto Lavarello as Leonzio. Following the will of the composer, there was a single performance, which obtained a good success.", "title": "" }, { "docid": "55085751", "text": "Gustavo primo, re di Svezia (\"Gustavus the First, King of Sweden\") is a three act opera seria by Baldassare Galuppi, with a libretto by Carlo Goldoni, fictionalising events in the life of Gustav I of Sweden. Composed in honour of the Genoese nobleman marchese Giovanni Giacomo Grimaldi, it premiered on 25 May 1740 at Venice's Teatro San Samuele. It was first recorded in 2003 by Karoly, Gonzalez, Cecchetti and the Capella Savaria Baroque Orchestra, conducted by Fabio Pirona.", "title": "" }, { "docid": "14141643", "text": "La figlia di Iorio (\"The Daughter of Iorio\"), sometimes written as La figlia di Jorio, is an opera in three acts by Alberto Franchetti to a libretto by Gabriele D'Annunzio. The libretto is a very close rendering of D'Annunzio's play of the same name. \"La figlia di Iorio\" premiered at La Scala on 29 March 1906, conducted by Leopoldo Mugnone. Although the play, which had premiered two years earlier, was considered one of D'Annunzio's greatest works, the opera did not achieve a comparable success and has been rarely performed since its day.", "title": "" }, { "docid": "2632909", "text": "Amadigi di Gaula (HWV 11) is a \"magic\" opera in three acts, with music by George Frideric Handel. It was the fifth Italian opera that Handel wrote for London and was composed during his stay at Burlington House in 1715. It is based on \"Amadis de Grèce\", a French tragédie-lyrique by André Cardinal Destouches and Antoine Houdar de la Motte. Charles Burney maintained near the end of the eighteenth century, \"Amadigi\" contained \"...more invention, variety and good composition, than in any one of the musical dramas of Handel which I have yet carefully and critically examined.”", "title": "" }, { "docid": "32710344", "text": "Il borgomastro di Saardam (The mayor of Saardam) is an 1827 melodramma giocoso (opera buffa) in two acts by Gaetano Donizetti. The libretto, by Domenico Gilardoni, was based on the 1818 play \"Le bourgmestre de Sardam, ou Les deux Pierres \" by Mélesville, Jean-Toussaint Merle and Eugène Cantiran de Boirie. Albert Lortzing's 1837 opera \"Zar und Zimmermann\" is ultimately based, via a German translation, on the same French play. The plot concerns a famous episode in the life of Peter the Great, in which he disguised himself under an assumed name as a worker in the shipyards of Saardam, and has certain similarities to Donizetti's earlier 1-act farce \"Il falegname di Livonia\".", "title": "" }, { "docid": "41334669", "text": "Charlotte Corday is an opera in three acts by Lorenzo Ferrero to an Italian-language libretto by Giuseppe Di Leva, written on commission from the Teatro dell'Opera di Roma for the 200th anniversary of the French Revolution which was commemorated in 1989.", "title": "" }, { "docid": "30860052", "text": "Admeto, re di Tessaglia (\"Admetus, King of Thessaly\", HWV 22) is a three-act opera written for the Royal Academy of Music with music composed by George Frideric Handel to an Italian-language libretto prepared by Nicola Haym. The story is partly based on Euripides' \"Alcestis\". The opera's first performance was at the Haymarket Theatre in London on 31 January 1727. The original cast included Faustina Bordoni as Alcestis and Francesca Cuzzoni as Antigona, as \"Admeto\" was the second of the five operas that Handel composed to feature specifically these two \"prime donne \" of the day.", "title": "" }, { "docid": "4828184", "text": "Poro, re dell'Indie (\"Porus, King of the Pakistani region\", HWV 28) is an opera seria in three acts by George Frideric Handel. The Italian-language libretto was adapted from \"Alessandro nell'Indie\" by Metastasio, and based on Alexander the Great's encounter with King Porus in 326 BC. The libretto had already been set to music by Leonardo Vinci in 1729 and by Antonio Vivaldi among others and was used as the text for more than sixty operas throughout the 18th century.", "title": "" }, { "docid": "3623194", "text": "The Nabucco-West pipeline (also referred to as the Turkey–Austria gas pipeline) was a proposed natural gas pipeline from the Turkish-Bulgarian border to Austria. It is a modification of the original Nabucco Pipeline project, which was to run from Erzurum in Turkey to Baumgarten an der March in Austria. The aim of the Nabucco pipeline is to diversify the natural gas suppliers and delivery routes for Europe, thus reducing European dependence on Russian energy. The original project was backed by several European Union member states and by the United States, and was seen as a rival to the South Stream pipeline project. The main supplier was expected to be Iraq, with potential supplies from Azerbaijan, Turkmenistan, and Egypt. The main supply for the Nabucco West was to be Shah Deniz gas through the proposed Trans-Anatolian gas pipeline (TANAP).", "title": "" }, { "docid": "38039560", "text": "Salvatore Giuliano is an opera in one act by Lorenzo Ferrero to an Italian-language libretto by Giuseppe Di Leva, which was conceived to be performed in tandem with Pietro Mascagni's \"Cavalleria rusticana\". The work was commissioned by the Teatro dell'Opera di Roma and premiered there on 25 January 1986.", "title": "" } ]
PLAIN-646	baked beans	[ { "docid": "MED-4509", "text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.", "title": "A meta-analysis of the effect of soy protein supplementation on serum lipids." }, { "docid": "MED-4510", "text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.", "title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials" } ]	[ { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-4991", "text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.", "title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..." }, { "docid": "MED-925", "text": "We present a case of a six-week-old infant who developed life-threatening complications after unintentional sodium bicarbonate intoxication. Baking soda was being used by the mother as a home remedy to \"help the baby burp.\" A review of the literature regarding the use (or misuse) of baking soda follows. Our patient, along with the other noted case reports, emphasizes the need for warnings on baking soda products whose labels recommend its use as an antacid. Poisonings must be high in the differential diagnosis of any patient, regardless of age, who presents with altered mental status or status epilepticus.", "title": "Baking soda: a potentially fatal home remedy." }, { "docid": "MED-2191", "text": "The effects of baking and boiling on the nutritional and antioxidant properties of three sweet potato cultivars (Beniazuma, Koganesengan, Kotobuki) cultivated in Turkey were investigated. The samples were analyzed for proximate composition, total phenolic content, ascorbic acid, β-carotene, antiradical activity, and free sugars. The dry matter, protein, and starch contents of the sweet potatoes were significantly changed by the treatments while the ash and crude fiber contents did not differ as significantly. The β-carotene contents of baked and boiled sweet potatoes were lower than those of fresh sweet potatoes; however, the total phenolic and ascorbic acid contents of the baked and boiled sweet potatoes were higher than those of the fresh samples. Generally, the antiradical activity of the sweet potatoes increased with the treatments. Sucrose, glucose, and fructose were quantified as free sugars in all fresh sweet potatoes; however, maltose was determined in the treated samples. In terms of the analyzed parameters, there were no explicit differences among the sweet potato cultivars.", "title": "Effects of baking and boiling on the nutritional and antioxidant properties of sweet potato [Ipomoea batatas (L.) Lam.] cultivars." }, { "docid": "MED-4782", "text": "A survey of a broad range of chocolate- and cocoa-containing products marketed in the United States was conducted to provide a more detailed analysis of flavan-3-ol monomers, oligomers, and polymers, which can be grouped into a class of compounds called procyanidins. Samples consisted of the three or four top-selling products within the following six categories: natural cocoa powder, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized for percent fat (% fat), percent nonfat cocoa solids (% NFCS), antioxidant level by ORAC, total polyphenols, epicatechin, catechin, total monomers, and flavan-3-ol oligomers and polymers (procyanidins). On a gram weight basis epicatechin and catechin content of the products follow in decreasing order: cocoa powder > baking chocolate > dark chocolate = baking chips > milk chocolate > chocolate syrup. Analysis of the monomer and oligomer profiles within product categories shows there are two types of profiles: (1) products that have high monomers with decreasing levels of oligomers and (2) products in which the level of dimers is equal to or greater than the monomers. Results show a strong correlation (R(2) = 0.834) of epicatechin to the level of % NFCS and also very good correlations for N = 2-5 oligomers to % NFCS. A weaker correlation was observed for catechin to % NFCS (R(2) = 0.680). Other analyses show a similar high degree of correlation with epicatechin and N = 2-5 oligomers to total polyphenols, with catechin being less well correlated to total polyphenols. A lesser but still good correlation exists between the calculated percent cacao (calcd % cacao) content, a proxy for percent cacao, and these same flavanol measures, with catechin again showing a lesser degree of correlation to calcd % cacao. Principal component analysis (PCA) shows that the products group discretely into five classes: (1) cocoa powder, (2) baking chocolate, (3) dark chocolate and semisweet chips, (4) milk chocolates, and (5) syrup. PCA also shows that most factors group closely together including the antioxidant activity, total polyphenols, and the flavan-3-ol measures with the exception of catechin and % fat in the product, which group separately. Because catechin distribution appears to be different from the other flavan-3-ol measures, an analysis of the epicatechin to catechin ratio was done, indicating there is a >5-fold variation in this measure across the products studied. The cocoa-containing products tested range from cocoa powder with 227.34 +/- 17.23 mg of procyanidins per serving to 25.75 +/- 9.91 mg of procyanidins per serving for chocolate syrup. These results are discussed with respect to other studies on commercial products, the bioavailability of the flavanols, and the possible role of processing on the amount of catechin in products.", "title": "Survey of commercially available chocolate- and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat co..." }, { "docid": "MED-924", "text": "Oral ingestion of baking soda (sodium bicarbonate) has been used for decades as a home remedy for acid indigestion. Excessive bicarbonate ingestion places patients at risk for a variety of metabolic derangements including metabolic alkalosis, hypokalemia, hypernatremia, and even hypoxia. The clinical presentation is highly variable but can include seizures, dysrhythmias, and cardiopulmonary arrest. We present two cases of severe metabolic alkalosis in patients with unsuspected antacid overdose. The presentation and pathophysiology of antacid-related metabolic alkalosis is reviewed.", "title": "Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose." }, { "docid": "MED-3584", "text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.", "title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults" }, { "docid": "MED-2140", "text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253", "title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study" }, { "docid": "MED-2209", "text": "This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.", "title": "Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica" }, { "docid": "MED-1880", "text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)." }, { "docid": "MED-3141", "text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.", "title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome." }, { "docid": "MED-5079", "text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.", "title": "Pinto bean consumption reduces biomarkers for heart disease risk." }, { "docid": "MED-2570", "text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(IcAs)483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(IcAs)483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(IcAs)483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.", "title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..." }, { "docid": "MED-4916", "text": "Agaritine (N-(gamma-L(+)-glutamyl)-4-hydroxymethyl-phenylhydrazine) was identified and quantified by high-pressure liquid chromatography and used as a marker for the occurrence of phenylhydrazine derivatives in the cultivated Agaricus bitorquis and A. garicus hortensis mushrooms. Although relatively high levels of agaritine (around 700 mg kg(-1)) could be found in freshly harvested A. bitorquis from early flushes, samples from supermarkets contained less agaritine. The content of 28 samples varied between 165 and 457 mg kg(-1), on average being 272 +/- 69 mg kg(-1). The highest amounts of agaritine were found in the skin of the cap and in the gills, the lowest being in the stem. There was no significant difference in agaritine content of the two mushroom species in our study. Pronounced reduction in agaritine content was observed during storage of mushrooms in the refrigerator or freezer, as well as during drying of the mushrooms. The degree of reduction was dependent on the length and condition of storage and was usually in the region 20-75%. No reduction in agaritine content was observed during freeze-drying. Depending on the cooking procedure, household processing of cultivated Agaricus mushrooms reduced the agaritine content to various degrees. Boiling extracted around 50% of the agaritine content into the cooking broth within 5min and degraded 20-25% of the original agaritine content of the mushrooms. Prolonged boiling, as when preparing a sauce, reduced the content in the solid mushroom further (around 10% left after 2h). Dry baking of the cultivated mushroom, a process similar to pizza baking, reduced the agaritine content by approximately 25%, whereas frying in oil or butter or deep frying resulted in a more marked reduction (35-70%). Microwave processing of the cultivated mushrooms reduced the agaritine content to one-third of the original level. Thus, the exposure to agaritine was substantially less when consuming processed Agaricus mushrooms as compared with consuming the raw mushrooms. However, it is not yet known to what extent agaritine and other phenylhydrazine derivatives occurring in the cultivated mushroom are degraded into other biologically active compounds during the cooking procedure.", "title": "Influence of storage and household processing on the agaritine content of the cultivated Agaricus mushroom." }, { "docid": "MED-3136", "text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.", "title": "Influence of frequent and long-term bean consumption on colonic function and fermentation." }, { "docid": "MED-2147", "text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.", "title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects." }, { "docid": "MED-2580", "text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.", "title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial" }, { "docid": "MED-2144", "text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.", "title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents." }, { "docid": "MED-2010", "text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.", "title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review." }, { "docid": "MED-5078", "text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.", "title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans." }, { "docid": "MED-2141", "text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population." }, { "docid": "MED-5080", "text": "Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.", "title": "Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities." }, { "docid": "MED-926", "text": "A case of severe metabolic alkalosis (MA) resulting from ingestion of baking soda (sodium bicarbonate) is presented. On admission to the emergency department, the patient was alert and stable with an initial examination that was remarkable only for carpopedal spasm. Shortly thereafter, the patient had a sudden, unexpected cardiopulmonary arrest. Following resuscitation, without administration of sodium bicarbonate, the arterial blood gas revealed a pH of 7.73, pO2 of 51 mm Hg, and pCO2 of 52 mm Hg. After admission to the intensive care unit, the patient's MA was corrected using IV 0.25 N hydrochloric acid. The patient remained comatose as a result of severe anoxic encephalopathy and died two weeks after admission. We believe this is the first reported case of severe MA resulting in sudden cardiopulmonary arrest in a previously ambulatory patient.", "title": "Severe metabolic alkalosis in the emergency department." }, { "docid": "MED-3810", "text": "The typical spices used in winter include nutmeg, cinnamon, clove and anise. These spices contain two groups of chemicals, the allylbenzenes and their isomers, the propenylbenzenes. It was suggested 40 years ago by Alexander Shulgin that these substances act as metabolic precursors of amphetamines. The biotransformation of these precursors to nitrogen-containing metabolites is reviewed. These reactions have not been reported in humans. Whether or not the pharmacology and toxicology of spices such as nutmeg can be explained on the basis of their allylbenzene or propenylbenzene content is speculative. Humans may be exposed to amphetamines derived from these precursors in forno, the formation during baking and cooking, for example in the preparation of Lebkuchen, or Christmas gingerbread. It is possible that this may be responsible, in part, for uplifting our mood in winter. However, the role of these aromatic substances, acting simply as odours, evoking old memories of winters past, cannot be ignored. Whether spices have a true pharmacological effect or they act as aromatherapy remains to be elucidated through clinical and laboratory studies.", "title": "Christmas gingerbread (Lebkuchen) and Christmas cheer--review of the potential role of mood elevating amphetamine-like compounds formed in vivo and..." }, { "docid": "MED-884", "text": "Approximately 75% of all kidney stones are composed primarily of calcium oxalate, and hyperoxaluria is a primary risk factor for this disorder. Nine types of raw and cooked vegetables were analyzed for oxalate using an enzymatic method. There was a high proportion of water-soluble oxalate in most of the tested raw vegetables. Boiling markedly reduced soluble oxalate content by 30-87% and was more effective than steaming (5-53%) and baking (used only for potatoes, no oxalate loss). An assessment of the oxalate content of cooking water used for boiling and steaming revealed an approximately 100% recovery of oxalate losses. The losses of insoluble oxalate during cooking varied greatly, ranging from 0 to 74%. Because soluble sources of oxalate appear to be better absorbed than insoluble sources, employing cooking methods that significantly reduce soluble oxalate may be an effective strategy for decreasing oxaluria in individuals predisposed to the development of kidney stones.", "title": "Effect of different cooking methods on vegetable oxalate content." }, { "docid": "MED-2185", "text": "Orange fleshed sweet potato (OFSP) has been identified as a good source of beta-carotene but the beta-carotene bioaccessibility is affected by processing. In this study, the effect of traditional heat processing methods on the microstructure and in vitro bioaccessibility of beta-carotene from OFSP were investigated. Bioaccessibility was determined using simulated in vitro digestion model followed by membrane filtration to separate the micellar fraction containing bioaccessible beta-carotene. Processing led to decrease in the amount of all-trans-beta-carotene and increase in 13-cis-beta-carotene. Processed OFSP had significantly higher (P < 0.05) bioaccessible beta-carotene compared to the raw forms. Bioaccessibility varied with processing treatments in the order; raw < baked < steamed/boiled < deep fried. Light microscopy showed that the microstructure of OFSP was disrupted by the processing methods employed. The cell walls of OFSP were sloughed by the traditional heat processing methods applied. The findings show that heat processing improves bioaccessibility of beta-carotene in OFSP and this was probably due to disruption of the tissue microstructure.", "title": "Microstructure and in vitro beta carotene bioaccessibility of heat processed orange fleshed sweet potato." }, { "docid": "MED-3132", "text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.", "title": "Legume promotion in counselling: an e-mail survey of dietitians." }, { "docid": "MED-4053", "text": "Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Occurrence of heterocyclic amines in cooked meat products." }, { "docid": "MED-2085", "text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.", "title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables." }, { "docid": "MED-5118", "text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.", "title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial." } ]
PLAIN-780	burgers	[ { "docid": "MED-4450", "text": "Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.", "title": "Post-diagnosis dietary factors and survival after invasive breast cancer" }, { "docid": "MED-3053", "text": "BACKGROUND: The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. OBJECTIVE: The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. DESIGN: Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. RESULTS: High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. CONCLUSIONS: The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at clinicaltrials.gov as NCT01516021.", "title": "Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans." }, { "docid": "MED-1253", "text": "OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19", "title": "Effects of soy as tofu vs meat on lipoprotein concentrations." }, { "docid": "MED-1615", "text": "Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors." }, { "docid": "MED-1252", "text": "The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol, 218 to 307 mg/dl. The diets were low in cholesterol, 200 mg/day, with 13 to 16% of energy as protein, 30 to 35% as fat, and a polyunsaturated to saturated fat ratio of 0.5. Of protein 65% was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats. Fresh egg yolk was added to balance the cholesterol content of the diets. Proteins from grains and vegetables were identical in both menus and contributed about 35% of dietary protein. Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol. Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups. Mean decreases in plasma cholesterol, 16 and 13%, for responders in the animal and soy groups were significant, p less than 0.01 and 0.05, respectively. Responders in both groups had higher initial plasma cholesterol values than nonresponders. Although plasma high-density lipoprotein cholesterol decreased slightly, the high-density lipoprotein cholesterol to cholesterol ratio (high-density lipoprotein cholesterol/total cholesterol) remained constant for most individuals. The hypocholesterolemic effects were similar for both animal and soy protein (p less than 0.05) and fat (p less than 0.05) while on the experimental diet. All groups significantly decreased dietary cholesterol (p less than 0.001).", "title": "Determinants of hypocholesterolemic response to soy and animal protein-based diets." }, { "docid": "MED-1257", "text": "Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.", "title": "Protein and coronary heart disease: the role of different protein sources." }, { "docid": "MED-1492", "text": "BACKGROUND: The benefits of reducing blood pressure are well established, but there remains uncertainty about whether the magnitude of the effect varies with the initial blood pressure level. The objective was to compare the risk reductions achieved by different blood pressure-lowering regimens among individuals with different baseline blood pressures. METHODS: Thirty-two randomized controlled trials were included and seven comparisons between different types of treatments were made. For each comparison, the primary prespecified analysis included calculation of summary estimates of effect using random-effects meta-analysis for major cardiovascular events in four groups defined by baseline SBP (<140, 140-159, 160-179, and ≥ 180 mmHg). RESULTS: There were 201 566 participants among whom 20 079 primary outcome events were observed. There was no evidence of differences in the proportionate risk reductions achieved with different blood pressure-lowering regimens across groups defined according to higher or lower levels of baseline SBP (all P for trend > 0.17). This finding was broadly consistent for comparisons of different regimens, for DBP categories, and for commonly used blood pressure cut-points. CONCLUSION: It appears unlikely that the effectiveness of blood pressure-lowering treatments depends substantively upon starting blood pressure level. As the majority of patients in the trials contributing to these overviews had a history of hypertension or were receiving background blood pressure-lowering therapy, the findings suggest that additional blood pressure reduction in hypertensive patients meeting initial blood pressure targets will produce further benefits. More broadly, the data are supportive of the utilization of blood pressure-lowering regimens in high-risk patients with and without hypertension.", "title": "The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline bloo..." }, { "docid": "MED-1858", "text": "As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as \"cup versus straw,\" and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.", "title": "Influence of drinking patterns of carbonated beverages on dental erosion." }, { "docid": "MED-4746", "text": "Americans consume about 5 billion hamburgers a year. It is presumed that most hamburgers are composed primarily of meat. The purpose of this study is to assess the content of 8 fast food hamburger brands using histologic methods. Eight different brands of hamburgers were evaluated for water content by weight and microscopically for recognizable tissue types. Glial fibrillary acidic protein (GFAP) staining was used to evaluate for brain tissue. Water content by weight ranged from 37.7% to 62.4% (mean, 49%). Meat content in the hamburgers ranged from 2.1% to 14.8% (median, 12.1%). The cost per gram of hamburger ranged from $0.02 to $0.16 (median, $0.03) and did not correlate with meat content. Electron microscopy showed relatively preserved skeletal muscle. A variety of tissue types besides skeletal muscle were observed including connective tissue (n = 8), blood vessels (n = 8), peripheral nerve (n = 8), adipose tissue (n = 7), plant material (n = 4), cartilage (n = 3), and bone (n = 2). In 2 hamburgers, intracellular parasites (Sarcocystis) were identified. The GFAP immunostaining was not observed in any of the hamburgers. Lipid content on oil-red-O staining was graded as 1+ (moderate) in 6 burgers and 2+ (marked) in 2 burgers. Fast food hamburgers are comprised of little meat (median, 12.1%). Approximately half of their weight is made up of water. Unexpected tissue types found in some hamburgers included bone, cartilage, and plant material; no brain tissue was present. Sarcocystis parasites were discovered in 2 hamburgers.", "title": "Fast food hamburgers: what are we really eating?" }, { "docid": "MED-4602", "text": "The strategy of \"manufacturing uncertainty\" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called \"product defense\" or \"litigation support.\" As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.", "title": "Manufactured uncertainty: protecting public health in the age of contested science and product defense." }, { "docid": "MED-1609", "text": "To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.", "title": "High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults." }, { "docid": "MED-702", "text": "AIM OF THE REVIEW: To systematically analyze the efficacy and safety of liraglutide for the treatment of diabetes mellitus in comparison to other mono- and combination therapies. METHOD: PubMed (any date) and EMBASE (all years) search was conducted with liraglutide as a search term. Phase III clinical trials retrieved by the two databases and resources posted in Drug@FDA website were evaluated with regard to outcomes of efficacy and safety. RESULTS: Eight Phase III clinical studies compared the efficacy and safety of liraglutide to other monotherapies or combinations. Liraglutide as monotherapy in doses of 0.9 mg or above showed a significantly superior reduction in HbA1C compared to monotherapies with glimepiride or glyburide. When liraglutide was used as add-on therapy to glimepiride in doses of 1.2 mg or above, the reduction of HbA1C was greater than that in the combination therapy of glimepiride and rosiglitazone. However, liraglutide as add-on therapy to metformin failed to show benefit over combination of metformin and glimepiride. Triple therapy of using liraglutide in addition to metformin plus either glimepiride or rosiglitazone resulted in additional benefit in HbA1C reduction. Most common adverse events were gastrointestinal disturbance such as nausea, vomit, diarrhea, and constipation. During the eight clinical studies, six cases of pancreatitis and five cases of cancer were reported in liraglutide arm, whereas there was one case of each of pancreatitis in exenatide and glimepiride arms, respectively, and one case of cancer in metformin plus sitagliptin arm. CONCLUSION: Liraglutide is a new therapeutic option to improve glycemic control in patients with type 2 diabetes. However, the present lack of evidence of durability of efficacy and long-term safety appear to limit its utility in the general treatment of type 2 diabetes at this time.", "title": "The efficacy and safety of liraglutide." }, { "docid": "MED-4451", "text": "Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.", "title": "Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish." }, { "docid": "MED-3228", "text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.", "title": "Dietary protein and bone health: harmonizing conflicting theories." }, { "docid": "MED-2726", "text": "The 2011 UN high-level meeting on non-communicable diseases (NCDs) called for multisectoral action including with the private sector and industry. However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent harm caused by the unhealthy commodity industries. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Profits and pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and drink industries." }, { "docid": "MED-4560", "text": "The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.", "title": "Preventing and arresting coronary atherosclerosis." }, { "docid": "MED-1611", "text": "A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.", "title": "Latest insights into the risk of cancer in diabetes" }, { "docid": "MED-4027", "text": "Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.", "title": "Dietary behavior and knowledge of dental erosion among Chinese adults" }, { "docid": "MED-4205", "text": "Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the \"chemical safety of meat and meat products\" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.", "title": "Chemical safety of meat and meat products." }, { "docid": "MED-2221", "text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.", "title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?" }, { "docid": "MED-4472", "text": "N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.", "title": "N-Nitroso compounds in the diet." }, { "docid": "MED-1801", "text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.", "title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein." }, { "docid": "MED-3054", "text": "The relationship between overeating, substance abuse and (behavioral) addiction is controversial. Medically established forms of addiction so far pertain to substance use disorders only. But the preliminary Diagnostic and Statistical Manual for Mental Disorders V (DSM V) suggests replacing the previous category 'Substance-Related Disorders' with 'Addiction and Related Disorders', thus for the first time allowing the diagnosis of behavioral addictions. In the past psychiatrists and psychologists have been reluctant to systematically delineate and classify the term behavioral addiction. However, there is a broad overlap between chemical and behavioral addiction including phenomenological, therapeutic, genetic, and neurobiological aspects. It is of interest to point out that the hormone leptin in itself has a pronounced effect on the reward system, thus suggesting an indirect link between overeating and 'chemical' addiction. Thus, leptin-deficient individuals could be classified as fulfilling criteria for food addiction. In our overview we first review psychological findings in chemical (substance-based) and subsequently in behavioral addiction to analyze the overlap. We discuss the diagnostic validity of food addiction, which in theory can be chemically and/or behaviorally based. Copyright © 2012 S. Karger GmbH, Freiburg.", "title": "Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction." }, { "docid": "MED-3237", "text": "The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "title": "Diet-induced metabolic acidosis." }, { "docid": "MED-5090", "text": "OBJECTIVE: To examine associations between the prevalence of degenerative arthritis and soft tissue disorders and consumption of meat and other foods among participants in the Adventist Health Study. METHODS: Unconditional logistic regression analysis is used to examine cross-sectional associations, adjusting for the effects of age, smoking, alcohol consumption, body mass index, use of sex hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft tissue disorders was 22.60 percent. Women had a higher prevalence than men and prevalence increased greatly with age. Smoking, higher body mass index, never use of contraceptive pills, and current hormone replacement therapy are associated with a higher prevalence of these disorders on multivariate analysis. Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and fruit consumption were weakly associated with increased risk. There were protective associations with nut and salad consumption. CONCLUSIONS: Greater meat consumption is associated with a higher prevalence of degenerative arthritis and soft tissue disorders in both male and female subjects of this population, as is hormone replacement therapy in women.", "title": "Associations between meat consumption and the prevalence of degenerative arthritis and soft tissue disorders in the adventist health study, Califor..." }, { "docid": "MED-1619", "text": "BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.", "title": "No evidence of insulin resistance in normal weight vegetarians. A case control study." }, { "docid": "MED-3226", "text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.", "title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load" }, { "docid": "MED-3052", "text": "Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.", "title": "Obesity and addiction: neurobiological overlaps." }, { "docid": "MED-1134", "text": "BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.", "title": "Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis." }, { "docid": "MED-3058", "text": "Recent research indicates similarities between obesity and addictive disorders on both the phenomenological and neurobiological level. In particular, neuroendocrine and imaging studies suggest a close link between the homeostatic regulation of appetite on the on hand, and motivation and reward expectancy on the other. In addition, findings from neuropsychological studies additionally demonstrate alterations of cognitive function in both obesity and addictive disorders that possibly contribute to a lack of control in resisting consumption. In this review, recent findings on overlapping neurobiological and phenomenological pathways are summarized and the impact with regard to new treatment approaches for obesity is discussed. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.", "title": "Implications from addiction research towards the understanding and treatment of obesity." }, { "docid": "MED-1254", "text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.", "title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation." }, { "docid": "MED-1853", "text": "PURPOSE: To measure the pH, titratable acidity, fluoride concentration and erosive potential of brewed teas. METHODS: Bag teas were purchased to represent black, green, citrus, fruity, and floral tea flavors from Tulsi, Bigelow, HyVee, Tazo, and Yogi brands and brewed (1 bag/240 ml) in boiling water for 3 minutes. The pH, titratable acidity, and fluoride concentrations were measured. Following these measurements, a representative tea from each flavor was selected for investigation of erosion potential. Six extracted human molars were randomly assigned to each tea. Teeth were painted with fingernail polish to expose a 1 x 4 mm window and then soaked in tea for a total of 25 hours with teas refreshed every 5 hours. Teeth were then sectioned using a microtome and photographed using a polarized light microscope. Lesion depths (i.e., eroded surfaces) were measured using Image Pro Plus software. Differences in physiochemical properties and lesion depths between beverages were investigated using one-way ANOVA with post-hoc Tukey's HSD test. Relationships among lesion depths and physiochemical properties were evaluated using the Pearson correlation test. RESULTS: pH, titratable acidity and fluoride concentrations differed between tea flavors (P < 0.05) and between brands (P < 0.05). Lesion depths produced by the citrus tea (83.1 +/- 10.3 microm) were greater than those produced by the fruity tea (56.5 +/- 6.1 microm); both teas produced greater depths than black (30.1 +/- 7.4 microm), floral (25.0 +/- 3.2 microm) or green (22.3 +/- 6.3 microm) teas (P < 0.05). pH (r = -0.96; P = 0.009) was inversely and titratable acidity (r = 0.97; P = 0.006) was positively associated with lesion depths.", "title": "Erosive potentials of brewed teas." }, { "docid": "MED-4408", "text": "The influence of protein oxidation, as measured by the dinitrophenylhydrazine (DNPH) method, on colour and texture changes during chill storage (2 degrees C, 12days) of cooked burger patties was studied. Extracts from arbutus-berries (Arbutus unedoL., AU), common hawthorns (Crataegus monogynaL., CM), dog roses (Rosa caninaL., RC) and elm-leaf blackberries (Rubus ulmifoliusSchott., RU) were prepared, added to burger patties (3% of total weight) and evaluated as inhibitors of protein oxidation and colour and texture changes. Negative (no added extract, C) and positive control (added quercetin; 230mg/kg, Q) groups were also considered. The significant increase of protein carbonyls during chill storage of control burger patties reflect the intense oxidative degradation of the muscle proteins. Concomitantly, an intense loss of redness and increase of hardness was found to take place in burger patties throughout refrigerated storage. Most fruit extracts as well as Q significantly reduced the formation of protein carbonyls and inhibited colour and texture deterioration during chill storage. Likely mechanisms through which protein oxidation could play a major role on colour and texture changes during chill storage of burger patties are discussed. Amongst the extracts, RC was most suitable for use as a functional ingredient in processed meats since it enhanced oxidative stability, colour and texture properties of burger patties with no apparent drawbacks. Copyright 2010 Elsevier Ltd. All rights reserved.", "title": "Protein oxidation in emulsified cooked burger patties with added fruit extracts: Influence on colour and texture deterioration during chill storage." }, { "docid": "MED-3230", "text": "OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.", "title": "Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores." }, { "docid": "MED-3235", "text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.", "title": "Alkaline diets favor lean tissue mass in older adults" }, { "docid": "MED-1618", "text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.", "title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..." }, { "docid": "MED-4203", "text": "Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.", "title": "Evolution of dietary antioxidants." }, { "docid": "MED-1494", "text": "Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈ 10 mm Hg lower, and DBP was ≈ 7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥ 140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.", "title": "Potent antihypertensive action of dietary flaxseed in hypertensive patients." }, { "docid": "MED-1136", "text": "1. Studies were carried out on six normal male subjects to determine the short-term effect of increasing the dietary consumption of animal protein on the urinary risk factors for stone-formation, namely, volume, pH, calcium oxalate, uric acid and glycosaminoglycans. 2. An increase of 34 g/day of animal protein in the diet significantly increased urinary calcium (23%) and oxalate (24%). Total urinary nitrogen increased by an average of 368 mmol/day. The accompanying increase in dietary purine (11 mmol of purine nitrogen/day) caused a 48% increase in the excretion of uric acid. 3. The overall relative probability of forming stones, calculated from a combination of the risk factors, was markedly increased (250%) throughout the period of high animal protein ingestion.", "title": "The effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract." }, { "docid": "MED-1137", "text": "The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.", "title": "Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)." }, { "docid": "MED-1610", "text": "The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite." }, { "docid": "MED-3051", "text": "The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI) studies have indicated that glucose consumption has some effect on the neuronal activity levels in the hypothalamus, this matter has not been investigated extensively yet. For instance, dose-dependency of the hypothalamic responses to glucose ingestion has not been addressed. We measured the effects of two different glucose loads on neuronal activity levels in the human hypothalamus using fMRI. After an overnight fast, the hypothalamus of 15 normal weight men was scanned continuously for 37 min. After 7 min, subjects ingested either water or a glucose solution containing 25 or 75 g of glucose. We observed a prolonged decrease of the fMRI signal in the hypothalamus, which started shortly after subjects began drinking the glucose solution and lasted for at least 30 min. Moreover, the observed response was dose-dependent: a larger glucose load resulted in a larger signal decrease. This effect was most pronounced in the upper anterior hypothalamus. In the upper posterior hypothalamus, the signal decrease was similar for both glucose loads. No effect was found in the lower hypothalamus. We suggest a possible relation between the observed hypothalamic response and changes in the blood insulin concentration.", "title": "Functional MRI of human hypothalamic responses following glucose ingestion." }, { "docid": "MED-4471", "text": "Some indoor activities increase the number concentration of small particles and, hence, enhance the dose delivered to the lungs. The received particle dose indoors may exceed noticeably the dose from ambient air under routine in-house activities like cooking. In the present work, the internal dose by inhalation of ultrafine and fine particles is assessed, using an appropriate mechanistic model of lung deposition, accommodating aerosol, and inhalation dynamics. The analysis is based on size distribution measurements (10-350 nm) of indoor and outdoor aerosol number concentrations in a typical residence in Athens, Greece. Four different cases are examined, namely, a cooking event, a no activity period indoors and the equivalent time periods outdoors. When the cooking event (frying of bacon-eggs with a gas fire) occurred, the amount of deposited particles deep into the lung of an individual indoors exceeded by up to 10 times the amount received by an individual at the same time period outdoors. The fine particle deposition depends on the level of physical exertion and the hygroscopic properties of the inhaled aerosol. The dose is not found linearly dependant on the indoor/outdoor concentrations during the cooking event, whereas it is during the no activity period. PRACTICAL IMPLICATIONS: The necessity for determining the dose in specific regions of the human lung, as well as the non-linear relationship between aerosol concentration and internal dose makes the application of dosimetry models important. Lung dose of fine and ultrafine particles, during a cooking event, is compared with the dose at no indoor activity and the dose received under outdoor exposure conditions. The dose is expressed in terms of number or surface of deposited particles. This permits to address the dosimetry of very small particles, which are released by many indoor sources but represent a slight fraction of the particulate matter mass. The enhancement of the internal dose resulting from fine and ultrafine particles generated during the cooking event vs. the dose when no indoor source is active is assessed. The results for those cases are also compared with the dose calculated for the measured aerosol outdoors.", "title": "Lung deposition of fine and ultrafine particles outdoors and indoors during a cooking event and a no activity period." }, { "docid": "MED-4355", "text": "Sixty percent of the U.S. population experiences acute diarrheal illness each year, but little is understood regarding public knowledge and beliefs about the causes and treatment of these diseases. We performed a telephone survey of 2117 Tennessee residents regarding knowledge and practices associated with diarrheal illness. Bloody stool, dehydration, and persistent symptoms were the most common reasons for which the respondents would seek medical care. Although most acute diarrheal disease is self-limited, overuse of antimicrobials for treatment is common. Few people believed that stool cultures (4.5%) or antibiotics (6.9%) are routinely necessary for diarrhea. Over 60% of respondents believed that food is the most common source of diarrhea. Three-fourths believed that it is normal for uncooked meat to contain bacteria, and 45% believed it is legal to sell such products. These results have implications for medical providers, regulators, and public health in the management and prevention of diarrheal disease.", "title": "Public knowledge and beliefs about diarrheal disease." }, { "docid": "MED-3046", "text": "Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.", "title": "Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study." }, { "docid": "MED-3059", "text": "AIMS: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling, but no studies have compared the effects of glucose and fructose. We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process. METHODS: Nine healthy, normal weight subjects underwent blood oxygenation level dependent (BOLD) fMRI measurements during either intravenous (IV) glucose (0.3 mg/kg), fructose (0.3 mg/kg) or saline, administered over 2 min in a randomized, double-blind, crossover study. Blood was sampled every 5 min during a baseline period and following infusion for 60 min in total for glucose, fructose, lactate and insulin levels. RESULTS: No significant brain BOLD signal changes were detected in response to IV saline. BOLD signal in the cortical control areas increased during glucose infusion (p = 0.002), corresponding with increased plasma glucose and insulin levels. In contrast, BOLD signal decreased in the cortical control areas during fructose infusion (p = 0.006), corresponding with increases of plasma fructose and lactate. Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus. CONCLUSION: In normal weight humans, cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose. Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake. © 2011 Blackwell Publishing Ltd.", "title": "Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans." }, { "docid": "MED-4407", "text": "Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice." }, { "docid": "MED-1860", "text": "To compare the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients, this double-blind randomized controlled trial was carried out. Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4+/-11.8 mm Hg at the beginning of the study to 112.7+/-5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6+/-14.9 to 127.3+/-8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group. The mean pulse pressure (PP) of the patients in the ST group decreased from 52.2+/-12.2 to 34.5+/-9.3 mm Hg (P-value <0.001) during the study, whereas in the BT group, it increased from 41.9+/-11.7 to 47.3+/-9.6 mm Hg (P-value=0.01). In conclusion, consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension. This study supports the results of similar studies in which antihypertensive effects have been shown for ST.", "title": "The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes." }, { "docid": "MED-1256", "text": "BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.", "title": "A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption." }, { "docid": "MED-3038", "text": "The effects of 50 mg naltrexone on eating and subjective appetite were assessed in a double-blind placebo-controlled study with 20 male volunteers. Appetite was monitored using a disguised digital balance connected to a micro-computer, which constantly monitored the amount of food remaining, and which automatically interrupted feeding for 30 s after every 50 g consumed to allow appetite ratings to be made. Half the subjects ate pasta with a cheese sauce, and the remainder pasta with a tomato sauce. Subjects ate significantly less of both foods after 50 mg naltrexone than in either the placebo condition or on the initial (familiarisation) day. Naltrexone also reduced the rated pleasantness of both foods, and reduced overall eating rate. When best-fit quadratic functions were used to describe changes in rated hunger in relation to intake within the meal, naltrexone abolished the positive linear component reflecting the initial stimulation of appetite without altering either intercept or the negative quadratic function. Although mood ratings suggested that naltrexone had a mild sedative effect, mood changes alone could not explain the effects of naltrexone on appetite. Overall, these data suggest a specific role for opioids in the stimulation of appetite through palatability.", "title": "Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect." }, { "docid": "MED-1650", "text": "Short abstract Campaigns to promote healthy eating are undermined by the ubiquity of processed, energy dense foods. A global strategy is now needed to tackle the rising prevalence of obesity", "title": "Tobacco and obesity epidemics: not so different after all?" }, { "docid": "MED-3597", "text": "Background Dietary trans fatty acids (dTFA) are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. Methodolgy/Prinicpal Findings We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999–2004) were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking). Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld with adjustment for confounders, was preserved across sex, age, and ethnicity strata, and held cross-sectionally and prospectively. Conclusions/Significance This study provides the first evidence linking dTFA with behavioral irritability and aggression. While confounding is always a concern in observational studies, factors including strength and consistency of association, biological gradient, temporality, and biological plausibility add weight to the prospect of a causal connection. Our results may have relevance to public policy determinations regarding dietary trans fats. Clinicaltrials.gov # NCT00330980", "title": "Trans Fat Consumption and Aggression" }, { "docid": "MED-4337", "text": "The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-α and IL-6 from human monocytes in vitro. To investigate what may differentiate inflammatory from non-inflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-α-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-α secretion in monocytes correlated with the content of both TLR2 (r 0·837) and TLR4 stimulants (r 0·748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.", "title": "The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like r..." }, { "docid": "MED-1871", "text": "In order to compare the antihypertensive effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa with captopril, a controlled and randomized clinical trial was done. Patients from 30 to 80 years old with diagnosed hypertension and without antihypertensive treatment for at least 1 month before were included. The experimental procedure consisted of the administration of an infusion prepared with 10 g of dry calyx from H. sabdariffa on 0.51 water (9.6 mg anthocyanins content), daily before breakfast, or captopril 25 mg twice a day, for 4 weeks. The outcome variables were tolerability, therapeutic effectiveness (diastolic reduction > or = 10 mm Hg) and, in the experimental group, urinary electrolytes modification. Ninety subjects were included, 15 withdrew from the study due to non-medical reasons; so, the analysis included 39 and 36 patients from the experimental and control group, respectively. The results showed that H. sabdariffa was able to decrease the systolic blood pressure (BP) from 139.05 to 123.73mm Hg (ANOVA p < 0.03) and the diastolic BP from 90.81 to 79.52mm Hg (ANOVA p < 0.06). At the end of the study, there were no significant differences between the BP detected in both treatment groups (ANOVA p > 0.25). The rates of therapeutic effectiveness were 0.7895 and 0.8438 with H. sabdariffa and captopril, respectively (chi2, p > 0.560), whilst the tolerability was 100% for both treatments. A natriuretic effect was observed with the experimental treatment. The obtained data confirm that the H. sabdariffa extract, standardized on 9.6mg of total anthocyanins, and captopril 50 mg/day, did not show significant differences relative to hypotensive effect, antihypertensive effectiveness, and tolerability.", "title": "Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and ..." }, { "docid": "MED-1616", "text": "The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.", "title": "Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials." }, { "docid": "MED-4556", "text": "Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.", "title": "Tolerable upper intake levels for trans fat, saturated fat, and cholesterol." }, { "docid": "MED-3229", "text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.", "title": "Protein intake, calcium balance and health consequences." }, { "docid": "MED-1864", "text": "The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information. HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000 to over 5,000 mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses. There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels. Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hypolipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C. Anthocyanins found in abundance in HS calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit.", "title": "Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies" }, { "docid": "MED-4976", "text": "Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.", "title": "Airborne mutagens produced by frying beef, pork and a soy-based food." }, { "docid": "MED-4676", "text": "A widespread misconception has been developing among the Canadian public and among physicians. It is increasingly believed that consumption of dietary cholesterol and egg yolks is harmless. There are good reasons for long-standing recommendations that dietary cholesterol should be limited to less than 200 mg/day; a single large egg yolk contains approximately 275 mg of cholesterol (more than a day’s worth of cholesterol). Although some studies showed no harm from consumption of eggs in healthy people, this outcome may have been due to lack of power to detect clinically relevant increases in a low-risk population. Moreover, the same studies showed that among participants who became diabetic during observation, consumption of one egg a day doubled their risk compared with less than one egg a week. Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries. Patients at risk of cardiovascular disease should limit their intake of cholesterol. Stopping the consumption of egg yolks after a stroke or myocardial infarction would be like quitting smoking after a diagnosis of lung cancer: a necessary action, but late. The evidence presented in the current review suggests that the widespread perception among the public and health care professionals that dietary cholesterol is benign is misplaced, and that improved education is needed to correct this misconception. Résumé Une idée fausse et généralisée se répand au sein du public canadien et des médecins, qui pensent de plus en plus que la consommation de cholestérol alimentaire et de jaunes d’œuf est inoffensive. Les recommandations de longue date qui préconisent de limiter le cholestérol alimentaire à moins de 200 mg/jour reposent sur de bonnes raisons. Un seul gros jaune d’œuf contient environ 275 mg de cholestérol (plus que la portion quotidienne de cholestérol). Même si certaines études ont démontré que la consommation d’œufs n’est pas nuisible chez les personnes en santé, ce résultat peut découler de l’absence de capacité à déceler des augmentations pertinentes sur le plan clinique au sein d’une population à faible risque. De plus, les mêmes études ont révélé que chez les participants devenus diabétiques pendant la période d’observation, la consommation d’un œuf par jour doublait leur risque par rapport à la consommation de moins d’un œuf par semaine. Le régime ne vise pas à éviter le cholestérol, mais surtout les effets postprandiaux du cholestérol, des gras saturés, du stress oxydant et de l’inflammation. Le fait de se concentrer à tort sur les lipides à jeun occulte trois enjeux. Le cholestérol alimentaire accroît la susceptibilité des lipoprotéines à faible densité à l’oxydation, accroît la lipémie postprandiale et potentialise les effets secondaires des graisses saturées alimentaires. Le cholestérol alimentaire, y compris les jaunes d’œuf, est nuisible pour les artères. Les patients vulnérables aux maladies cardiovasculaires devraient limiter leur consommation de cholestérol. Le fait d’arrêter de consommer des jaunes d’œuf après un accident vasculaire cérébral ou un infarctus du myocarde s’apparenterait à arrêter de fumer après un diagnostic de cancer du poumon : c’est un geste nécessaire, mais entrepris tardivement. D’après les données probantes présentées dans la présente analyse, la perception généralisée du public et des professionnels de la santé selon laquelle le cholestérol alimentaire est un mal bénin est une idée fausse, et une meilleure information s’impose pour la corriger.", "title": "Dietary cholesterol and egg yolks: Not for patients at risk of vascular disease" }, { "docid": "MED-4559", "text": "The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.", "title": "Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?" }, { "docid": "MED-1617", "text": "Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.", "title": "Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women" }, { "docid": "MED-3599", "text": "The dietary intake of industrially-produced trans fatty acids (IP-TFA) was estimated for the US population (aged 2 years or more), children (aged 2-5 years) and teenage boys (aged 13-18 years) using the 2003-2006 National Health and Nutrition Examination Survey (NHANES) food consumption database, market share information and trans fat levels based on label survey data and analytical data for packaged and in-store purchased foods. For fast foods, a Monte Carlo model was used to estimate IP-TFA intake. Further, the intake of trans fat was also estimated using trans fat levels reported in the US Department of Agriculture (USDA) National Nutrient Database for Standard Reference, Release 22 (SR 22, 2009) and the 2003-2006 NHANES food consumption database. The cumulative intake of IP-TFA was estimated to be 1.3 g per person per day (g/p/d) at the mean for the US population. Based on this estimate, the mean dietary intake of IP-TFA has decreased significantly from that cited in the 2003 US Food and Drug Administration (FDA) final rule that established labelling requirements for trans fat (4.6 g/p/d for adults). Although the overall intake of IP-TFA has decreased as a result of the implementation of labelling requirements, individuals with certain dietary habits may still consume high levels of IP-TFA if certain brands or types of food products are frequently chosen.", "title": "Updated estimate of trans fat intake by the US population." }, { "docid": "MED-4831", "text": "Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.", "title": "Effects of plant-based diets on plasma lipids." }, { "docid": "MED-1249", "text": "The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.", "title": "Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women." }, { "docid": "MED-1613", "text": "The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.", "title": "Taiwanese vegetarians have higher insulin sensitivity than omnivores." }, { "docid": "MED-5328", "text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.", "title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2" }, { "docid": "MED-1612", "text": "Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.", "title": "Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load." }, { "docid": "MED-1614", "text": "AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.", "title": "Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores." }, { "docid": "MED-1250", "text": "The effect of plant and animal protein on blood lipid levels was investigated in eight healthy normolipidemic men aged 18 to 27 yr. All subjects were fed both plant and animal protein diets in a cross-over design. Each diet was consumed for a 21-day period. Proteins from commonly used plant sources made up the plant protein diet. Beef protein was substituted for 55% of the plant proteins in the animal protein diet. Fasting venous blood samples were collected at the beginning of the study and at 7-day intervals throughout the 42-day study. Serum was analyzed for total cholesterol and triglycerides. Plasma low-density and high-density lipoprotein cholesterol were determined. There were not any statistically significant differences in mean serum total cholesterol or mean plasma low-density lipoprotein cholesterol when subjects consumed the diets. Mean plasma high-density lipoprotein cholesterol levels were significantly (p less than 0.05) elevated at the end of the 21-day period when the animal protein diet was consumed (48 +/- 3 mg/dl) compared to the period when the plant protein diet was fed (42 +/- 2 mg/dl). Mean serum triglyceride values were significantly (p less than 0.05) increased at day 7 of the plant protein diet period (136 +/- 19 mg/dl) compared to the same time period when the animal protein diet was consumed (84 +/- 12 mg/dl). The results of the study indicated that the ingestion of a diet in which 55% of the protein was supplied by beef protein was not associated with a hypercholesterolemic effect in healthy normolipidemic young men.", "title": "A comparison of the effect of diets containing beef protein and plant proteins on blood lipids of healthy young men." }, { "docid": "MED-1857", "text": "BACKGROUND/OBJECTIVES: Investigations about possible correlations between vegetarian diet and periodontal conditions are rare and characterized by small case numbers. The aim of this clinical study was to investigate the influence of a vegetarian diet on periodontal parameters with an appropriate sample size. SUBJECTS/METHODS: A total of 200 patients, 100 vegetarians and 100 non-vegetarians, were included in the study. All patients were examined including a full mouth assessment of the periodontal and dental conditions. In addition, a questionnaire was handed out to ask for patients' oral hygiene habits and level of education. For statistical analysis the Mann-Whitney Test (χ(2) for analysis of the questionnaire) was applied (level of significance: P<0.05). RESULTS: Well known periodontal risk factors like age, gender and smoking habits were equally distributed within each group (71 females, 29 males, respectively and 10 smokers in each group; mean age: 41.45 years vegetarians versus 41.72 years non-vegetarians). Vegetarians had significantly lower probing pocket depths (P=0.039), bleeding on probing (P=0.001), periodontal screening index (P=0.012), a better hygiene index (P<0.001) and less mobile teeth (P=0.013). Dental examinations revealed significantly less missing teeth (P=0.018) but also more decayed (P=0.001) and eroded (P=0.026) teeth in vegetarians. Furthermore, vegetarians had a higher level of education (P<0.001), but visited dentists significantly less frequent. CONCLUSIONS: Vegetarians revealed better periodontal conditions (less inflammation signs, less periodontal damage and a better dental home care). However, it should be considered that vegetarians are not only avoiding meat in their nutrition but are also characterized by an overall healthier life style.", "title": "Periodontal conditions in vegetarians: a clinical study." }, { "docid": "MED-1620", "text": "Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767", "title": "A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women" }, { "docid": "MED-1133", "text": "Background The last nationally representative assessment of kidney stone prevalence in the United States occurred in 1994. After a 13-yr hiatus, the National Health and Nutrition Examination Survey (NHANES) reinitiated data collection regarding kidney stone history. Objective Describe the current prevalence of stone disease in the United States, and identify factors associated with a history of kidney stones. Design, setting, and participants A cross-sectional analysis of responses to the 2007–2010 NHANES (n = 12 110). Outcome measurements and statistical analysis Self-reported history of kidney stones. Percent prevalence was calculated and multivariable models were used to identify factors associated with a history of kidney stones. Results and limitations The prevalence of kidney stones was 8.8% (95% confidence interval [CI], 8.1–9.5). Among men, the prevalence of stones was 10.6% (95% CI, 9.4–11.9), compared with 7.1% (95% CI, 6.4–7.8) among women. Kidney stones were more common among obese than normal-weight individuals (11.2% [95% CI, 10.0–12.3] compared with 6.1% [95% CI, 4.8–7.4], respectively; p < 0.001). Black, non-Hispanic and Hispanic individuals were less likely to report a history of stone disease than were white, non-Hispanic individuals (black, non-Hispanic: odds ratio [OR]: 0.37 [95% CI, 0.28–0.49], p < 0.001; Hispanic: OR: 0.60 [95% CI, 0.49–0.73], p < 0.001). Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones. Conclusions Kidney stones affect approximately 1 in 11 people in the United States. These data represent a marked increase in stone disease compared with the NHANES III cohort, particularly in black, non-Hispanic and Hispanic individuals. Diet and lifestyle factors likely play an important role in the changing epidemiology of kidney stones.", "title": "Prevalence of Kidney Stones in the United States" }, { "docid": "MED-4975", "text": "BACKGROUND: Children from low-income families may be subject to high exposures to polycyclic aromatic hydrocarbons (PAH) which can lead to respiratory disorders. This study aims to establish methods for assessing total PAH exposure of asthmatic and non-asthmatic children from low-income families; to estimate serum PAH concentrations of these children, and to estimate the relative importance of the environmental pathways for PAH exposure. MATERIALS AND METHODS: A total of 75 (61 asthmatic, 14 non-asthmatic) Saudi children 15 years old and below were included to participate in this cross-sectional study. Each participant answered a generalized questionnaire with dietary questions. Serum PAH were measured using HPLC with UV detection. RESULTS: Serum naphthalene and pyrene were significantly elevated among asthmatic children (p-values = 0.007 and 0.01, respectively). Serum acenaphthylene, fluorine and 1,2-benzanthracene, on the other hand, were significantly higher among non-asthmatics (p-values = 0.001, 0.04 and 0.03, respectively). There was a significant correlation between the presence of a smoker in the family and serum concentrations of carbazole, pyrene, 1,2-benzanthracene and benzacephenanthrylene (R = 0.37, 0.45, 0.43, 0.33; p-values = 0.01, 0.0002, 0.003 and 0.025, respectively). Significant correlations were elicited between daily meat intake and serum levels of acenaphthylene, benzopyrene and 1,2-benzanthracene (R = 0.27, 0.27, 0.33; p-values = 0.02 and < 0.001, respectively). CONCLUSION: Among the children, serum PAH were significantly correlated to meat intake as well as presence of smokers at home. Public health awareness should be enhanced by educating parents to take certain precautions at home, such as preventing indoor smoking and reducing the intake of grilled and smoked meat by children so as to decrease their exposure to carcinogenic PAH.", "title": "Serum polycyclic aromatic hydrocarbons among children with and without asthma: correlation to environmental and dietary factors." }, { "docid": "MED-1138", "text": "PURPOSE: We compared the effect of 3 animal protein sources on urinary stone risk. MATERIALS AND METHODS: A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. RESULTS: Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). CONCLUSIONS: Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "title": "Animal protein and the risk of kidney stones: a comparative metabolic study of animal protein sources." }, { "docid": "MED-4973", "text": "Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for assessing human exposure to PAHs. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) uses OH-PAHs to establish reference range concentrations for the US population, and to set benchmarks for future epidemiologic and biomonitoring studies. For the years 2001 and 2002, 22 OH-PAH metabolites were measured in urine specimens from 2748 NHANES participants. Percentages of samples with detectable levels ranged from nearly 100% for metabolites of naphthalene, fluorene, phenanthrene, and pyrene, to less than 5% for metabolites from parent compounds with higher molecular weight such as chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The geometric mean for 1-hydroxypyrene (1-PYR)--the most commonly used biomarker for PAH exposure--was 49.6 ng/L urine, or 46.4 ng/g creatinine. Children (ages 6-11) generally had higher levels than did adolescents (ages 12-19) or adults (ages 20 and older). Model-adjusted, least-square geometric means for 1-PYR were 87, 53 and 43 ng/L for children, adolescents (ages 12-19) and adults (ages 20 years and older), respectively. Log-transformed concentrations for major detectable OH-PAHs were significantly correlated with each other. The correlation coefficients between 1-PYR and other metabolites ranging from 0.17 to 0.63 support the use of 1-PYR as a useful surrogate representing PAH exposure.", "title": "Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population." }, { "docid": "MED-4411", "text": "Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.", "title": "Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial." }, { "docid": "MED-3050", "text": "Background: Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. Objective: We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream–based milkshake and examined the influence of adipose tissue and the specificity of this relation. Design: Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Results: Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Conclusions: Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.", "title": "Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream–based milkshake" }, { "docid": "MED-1651", "text": "Background Limited information is available regarding the impact of candy consumption on health. The purpose of this study was to investigate associations between typical frequency of candy consumption and body weight status and select cardiovascular risk factors among adults in the United States. Methods Using data collected in the 2003–2006 National Health and Nutrition Examination Surveys (NHANES), adults were categorized as infrequent (≤ 3 eating occasions [EO]/month), moderate (> 3 EO/month and ≤ 3.5 EO/week), or frequent (> 3.5 EO/week) candy consumers based on the combined frequency of chocolate and other candy consumption over the previous 12 months. Weight and adiposity status were analyzed using logistic regression models, and blood pressure, lipids, and insulin sensitivity were analyzed using linear regression models. Models were adjusted for age, sex and race/ethnicity, and also for additional covariates with potential associations with the outcomes. Appropriate statistical weights were used to yield results generalizable to the US population. Results Frequency of candy consumption was not associated with the risk of obesity, overweight/obesity, elevated waist circumference, elevated skinfold thickness, blood pressure, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol, triglycerides, or insulin resistance. Increased frequency of candy consumption was associated with higher energy intakes and higher energy adjusted intakes of carbohydrates, total sugars and added sugars, total fat, saturated fatty acids and monounsaturated fatty acids (p < 0.05), and lower adjusted intakes of protein and cholesterol (p < 0.001). Conclusions Increased frequency of candy consumption among adults in the United States was not associated with objective measures of adiposity or select cardiovascular risk factors, despite associated dietary differences. Given the cross-sectional study design, however, it cannot be concluded that candy consumption does not cause obesity or untoward levels of cardiovascular risk markers. The lack of an association between frequency of candy consumption and cardiovascular risk factors could be due to reduced intake of candy among the overweight due to dieting or a health professional’s recommendations. Additionally, it is important to note that the analysis was based on frequency of candy consumption and not amount of candy consumed. Longitudinal studies are needed to confirm the lack of associations between frequency of candy consumption and cardiovascular risk factors.", "title": "Body weight status and cardiovascular risk factors in adults by frequency of candy consumption" }, { "docid": "MED-3232", "text": "High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: 1) evaluate the cross-sectional relation between DAL and BMD; 2) determine whether calcium intake modifies this association. Men (n=1218) and women (n=907) ≥60y were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2–24h recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3y. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend=0.04). No associations were observed with PRALtotal at any BMD site (P-range: 0.38–0.82). Among men, no significant associations were observed of BMD with NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p=0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men <800 mg/d dietary calcium (p=0.02); and no associations ≥800 mg/d (p=0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intakes in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.", "title": "Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium" }, { "docid": "MED-4333", "text": "OBJECTIVE To evaluate the changes in circulating endotoxin after a high–saturated fat meal to determine whether these effects depend on metabolic disease state. RESEARCH DESIGN AND METHODS Subjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.8 years [mean ± SD], BMI 24.9 ± 3.2 kg/m2, n = 9; obese: age 43.8 ± 9.5 years, BMI 33.3 ± 2.5 kg/m2, n = 15; impaired glucose tolerance [IGT]: age 41.7 ± 11.3 years, BMI 32.0 ± 4.5 kg/m2, n = 12; type 2 diabetic: age 45.4 ± 10.1 years, BMI 30.3 ± 4.5 kg/m2, n = 18). Blood was collected before (0 h) and after the meal (1–4 h) for analysis. RESULTS Baseline endotoxin was significantly higher in the type 2 diabetic and IGT subjects than in NOC subjects, with baseline circulating endotoxin levels 60.6% higher in type 2 diabetic subjects than in NOC subjects (P < 0.05). Ingestion of a high-fat meal led to a significant rise in endotoxin levels in type 2 diabetic, IGT, and obese subjects over the 4-h time period (P < 0.05). These findings also showed that, at 4 h after a meal, type 2 diabetic subjects had higher circulating endotoxin levels (125.4%↑) than NOC subjects (P < 0.05). CONCLUSIONS These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.", "title": "High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects" }, { "docid": "MED-3231", "text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.", "title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?" }, { "docid": "MED-4974", "text": "Roasting is a crucial step for the production of coffee, as it enables the development of color, aroma, and flavor, which are essential for the characterization of the coffee quality. At the same time, roasting may lead to the formation of not desirable compounds, such as polycyclic aromatic hydrocarbons (PAHs). In this paper, we report a method for PAHs determination in coffee brew, based on saponification and liquid-liquid extraction with small volumes of hexane, with exclusion of further processes of purification since we analyze the extract by gas chromatography with mass spectrometric detectors in the single ion monitoring mode (SIM). The total concentration of the 28 compounds investigated, expressed as the sum of concentrations (SigmaPAH), in coffee brew varies from 0.52 to 1.8 microg/l. Carcinogenic PAHs, expressed as B[a]Peq ranged from 0.008 to 0.060 microg/l. The results indicate that coffee contributes with very insignificant quantities to the daily human intake of carcinogenic PAHs. The values of calculated isomeric ratios confirm that the PAHs identified in most of the coffee samples originate from high temperature processes.", "title": "Polycyclic aromatic hydrocarbons (PAHs) in coffee brew samples: analytical method by GC-MS, profile, levels and sources." }, { "docid": "MED-4553", "text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.", "title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?" }, { "docid": "MED-1495", "text": "Response surface methodology was used to study the effect of flaxseed flour (FS) and tomato paste (TP) addition, from 0 to 10% and 0 to 20% respectively, on beef patty quality characteristics. The assessed quality characteristics were color (L, a, and b), pH and texture profile analysis (TPA). Also, sensory analysis was performed for the assessment of color, juiciness, firmness, and general acceptance. FS addition reduced L and a values and decreased weight loss of cooked products (P<0.05). An opposite effect was observed when TP was added (P<0.05). All TPA parameters decreased when percentages of FS and TP were increased in the formulation of beef patties. Furthermore, FS and TP addition adversely affected the sensory characteristics of the cooked product (P<0.05); nevertheless, all sensory characteristics evaluated had an acceptable score (>5.6). Thus FS and TP are ingredients that can be used in beef patty preparation. Copyright © 2014 Elsevier Ltd. All rights reserved.", "title": "Response surface methodology for predicting quality characteristics of beef patties added with flaxseed and tomato paste." }, { "docid": "MED-3236", "text": "A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.", "title": "Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians." }, { "docid": "MED-3227", "text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.", "title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women." }, { "docid": "MED-1491", "text": "The potential to increase n-3 fatty acid (FA) intake via flaxseed fed pork is underestimated when restricted to pure longissimus muscle, whereas a combination of muscle and adipose tissue is typically consumed. Presently, the FA content of pigs fed 0%, 5% and 10% dietary flaxseed for 11 weeks was measured in loin, picnic and butt primals (lean muscle with epimysium (L), L plus seam fat (LS), and LS plus 5 mm backfat (LSS)). The n-3 FA content necessary for an enrichment claim in Canada (300 mg/100 g serving) was exceeded in L from all primals when feeding 5% flaxseed, being 4 fold that of controls (P<0.001), with further enrichment from inclusion of associated adipose tissues (P<0.001). Increasing flaxseed feeding levels in combination with adipose tissue inclusion amplified total long chain n-3 FA (P<0.05), particularly 20:5n-3 and 22:5n-3. Flaxseed-fed n-3 FA enriched pork can contribute substantially to daily long chain n-3 FA intakes, particularly for societies with typically low seafood consumption. © 2013.", "title": "Flaxseed fed pork: n-3 fatty acid enrichment and contribution to dietary recommendations." }, { "docid": "MED-3044", "text": "OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.", "title": "Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli." }, { "docid": "MED-4206", "text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.", "title": "Vegetarian diets and public health: biomarker and redox connections." }, { "docid": "MED-4722", "text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.", "title": "Dietary protein and bone health: a systematic review and meta-analysis." }, { "docid": "MED-1258", "text": "Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.", "title": "The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia." }, { "docid": "MED-1859", "text": "Response surface methodology was used to investigate the effect and interactions of processing variables such as roselle extract (0.1-1.3%), soybean oil (5-20%) on physicochemical, textural and sensory properties of cooked pork patties. It was found that reduction in thickness, pH, L* and b* values decreased; however, water-holding capacity, reduction in diameter and a* values increased, respectively, as the amount of roselle increased. Soybean oil addition increased water-holding capacity, reduction in thickness, b* values of the patties. The hardness depended on the roselle and soybean oil added, as its linear effect was negative at p<0.01. The preference of color, tenderness, juiciness, and overall quality depend on the addition of roselle and soybean oil. The maximum overall quality score (5.42) was observed when 12.5 g of soybean oil and 0.7 g of roselle extract was added. The results of this optimization study would be useful for meat industry that tends to increase the product yield for patties using the optimum levels of ingredients by RSM. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Roselle (Hibiscus sabdariffa L.) and soybean oil effects on quality characteristics of pork patties studied by response surface methodology." }, { "docid": "MED-3057", "text": "The ongoing epidemics of obesity is one main health concern of the present time. Overeating in some obese individuals shares similarities with the loss of control and compulsive behavior observed in drug-addicted subjects, suggesting that obesity may involve food addiction. Here, we review the contributions provided by the use of positron emission tomography to the current understanding of the cerebral control of obesity and food intake in humans. The available studies have shown that multiple areas in the brain are involved with the reward properties of food, such as prefrontal, orbitofrontal, somatosensory cortices, insula, thalamus, hypothalamus, amygdala, and others. This review summarizes the current evidence, supporting the concepts that i) regions involved in the somatosensory response to food sight, taste, and smell are activated by palatable foods and may be hyperresponsive in obese individuals, ii) areas controlling executive drive seem to overreact to the anticipation of pleasure during cue exposure, and iii) those involved in cognitive control and inhibitory behavior may be resistant to the perception of reward after food exposure in obese subjects. All of these features may stimulate, for different reasons, ingestion of highly palatable and energy-rich foods. Though these same regions are similarly involved in drug abusers and game-addicted individuals, any direct resemblance may be an oversimplification, especially as the heterogeneities between studies and the prevalent exclusion of sensitive groups still limit a coherent interpretation of the findings. Further work is required to comprehensively tackle the multifaceted phenotype of obesity and identify the role of food dependency in its pathophysiology. Copyright © 2012 S. Karger GmbH, Freiburg.", "title": "Brain PET imaging in obesity and food addiction: current evidence and hypothesis." }, { "docid": "MED-1493", "text": "Presence of omega-3, omega-6 rich oil, alpha-linoleic acid, dietary fibers, secoisolariciresinol diglucoside, protein and minerals in flaxseed constitute a very strong basis for the utilization of flaxseed in various food preparations as a curative agent. An extensive body of literature illustrates that flaxseed has gained a significant position in the domain of nutritional sciences owing to its pivotal role as an antioxidant agent. The review discusses at length, numerous health benefits of flaxseed typically focusing its preventive role against cardiovascular diseases, cancer, diabetes and enhancement of spatial memory. Massive increase in the size of population with a special emphasize to the developing countries, there is an urge for exploration of the alternative dietary resources that can meet the dietary and nutritional needs of forthcoming generations. With respect to its remarkable nutritional importance, the review in question enables researchers engaged in nutritional sciences to further investigate the therapeutic value of flaxseed functional components and their dietary application in various food products and availability in processed foods as well as in the human cell line.", "title": "Flaxseed - a miraculous defense against some critical maladies." }, { "docid": "MED-1135", "text": "The hypothesis that the incidence of calcium stone disease is related to the consumption of animal protein has been examined. Within the male population, recurrent idiopathic stone formers consumed more animal protein than did normal subjects. Single stone formers had animal protein intakes intermediate between those of normal men and those of recurrent stone formers. A high animal protein intake caused a significant increase in the urinary excretion of calcium, oxalate and uric acid, 3 of the 6 main urinary risk factors for calcium stone formation. The overall relative probability of forming stones, calculated from the combination of the 6 main urinary risk factors, was markedly increased by a high animal protein diet. Conversely, a low animal protein intake, such as taken by vegetarians, was associated with a low excretion of calcium, oxalate and uric acid and a low relative probability of forming stones.", "title": "Should recurrent calcium oxalate stone formers become vegetarians?" }, { "docid": "MED-4299", "text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.", "title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention." }, { "docid": "MED-3055", "text": "Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects-partly mediated by dopamine increases in the limbic system-that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioural inhibition), stress reactivity, and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that shed light on the role of dopamine in drug addiction and in obesity, and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.", "title": "Food and drug reward: overlapping circuits in human obesity and addiction." }, { "docid": "MED-3056", "text": "Opioids are important in reward processes leading to addictive behavior such as self-administration of opioids and other drugs of abuse including nicotine and alcohol. Opioids are also involved in a broadly distributed neural network that regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In this sense, opioids are particularly implicated in the modulation of highly palatable foods, and opioid antagonists attenuate both addictive drug taking and appetite for palatable food. Thus, craving for palatable food could be considered as a form of opioid-related addiction. There are three main families of opioid receptors (µ, ĸ, and δ) of which µ-receptors are most strongly implicated in reward. Administration of selective µ-agonists into the NAcc of rodents induces feeding even in satiated animals, while administration of µ-antagonists reduces food intake. Pharmacological studies also suggest a role for ĸ- and δ-opioid receptors. Preliminary data from transgenic knockout models suggest that mice lacking some of these receptors are resistant to high-fat diet-induced obesity. Copyright © 2012 S. Karger GmbH, Freiburg.", "title": "The opioid system and food intake: homeostatic and hedonic mechanisms." }, { "docid": "MED-3233", "text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.", "title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..." }, { "docid": "MED-3060", "text": "Context Research has implicated an addictive process in the development and maintenance of obesity. Although parallels in neural functioning between obesity and substance dependence have been found, no studies have examined the neural correlates of addictive-like eating behavior. Objective To test the hypothesis that elevated “food addiction” scores are associated with similar patterns of neural activation as substance dependence. Design Between-Subjects fMRI study. Participants Forty-eight healthy adolescent females ranging from lean to obese recruited for a healthy weight maintenance trial. Main Outcome Measure The relation between elevated “food addiction” scores and blood oxygen level-dependent fMRI activation in response to receipt and anticipated receipt of palatable food (chocolate milkshake). Results Food addiction scores (N = 39) correlated with greater activation in the anterior cingulate cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala in response to anticipated receipt of food (P <0.05, false-discovery rate (FDR) corrected for multiple comparisons in small volumes). Participants with higher (n=15) versus lower (n=11) food addiction scores showed greater activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to anticipated receipt of food, but less activation in the lateral OFC in response to receipt of food (pFDR <0.05). Conclusions Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence; elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake.", "title": "The Neural Correlates of “Food Addiction”" }, { "docid": "MED-3598", "text": "Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.", "title": "A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD." } ]	[ { "docid": "MED-4972", "text": "Heterocyclic amines (HCAs), compounds formed when meat is cooked at high temperatures particularly through pan frying, grilling, or barbequing, pose a potential carcinogenic risk to the public. It is unclear whether there is any level at which consumption of HCAs can be considered safe. Efforts to measure these compounds mainly include cooking studies under laboratory conditions and some measurement of home-cooked foods, but analysis of commercially cooked foods has been minimal. Attempts to estimate exposure of the public to these compounds must take into consideration dining outside the home, which could result in significant exposure for some individuals. We surveyed at least 9 locations each of 7 popular chain restaurants (McDonald's, Burger King, Chick-fil-A, Chili's, TGI Friday's, Outback Steakhouse, and Applebee's) in California, collecting one or two entrees from each location. Entrees were analyzed for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using high-performance liquid chromatography tandem mass spectrometry. All 100 samples contained PhIP. Concentrations were variable within and between entrees and ranged from 0.08 to 43.2 ng/g. When factoring in the weight of the entrees, absolute levels of PhIP reached over 1,000 ng for some entrees. Potential strategies for reducing exposure include the avoidance of meats cooked using methods that are known to form PhIP.", "title": "Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California." }, { "docid": "MED-2391", "text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.", "title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA" }, { "docid": "MED-2027", "text": "Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance. © 2014 American Society for Parenteral and Enteral Nutrition.", "title": "Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity." }, { "docid": "MED-4499", "text": "Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy were used to study the cell injury and inactivation of Campylobacter jejuni from exposure to antioxidants from garlic. C. jejuni was treated with various concentrations of garlic concentrate and garlic-derived organosulfur compounds in growth media and saline at 4, 22, and 35°C. The antimicrobial activities of the diallyl sulfides increased with the number of sulfur atoms (diallyl sulfide < diallyl disulfide < diallyl trisulfide). FT-IR spectroscopy confirmed that organosulfur compounds are responsible for the substantial antimicrobial activity of garlic, much greater than those of garlic phenolic compounds, as indicated by changes in the spectral features of proteins, lipids, and polysaccharides in the bacterial cell membranes. Confocal Raman microscopy (532-nm-gold-particle substrate) and Raman mapping of a single bacterium confirmed the intracellular uptake of sulfur and phenolic components. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to verify cell damage. Principal-component analysis (PCA), discriminant function analysis (DFA), and soft independent modeling of class analogs (SIMCA) were performed, and results were cross validated to differentiate bacteria based upon the degree of cell injury. Partial least-squares regression (PLSR) was employed to quantify and predict actual numbers of healthy and injured bacterial cells remaining following treatment. PLSR-based loading plots were investigated to further verify the changes in the cell membrane of C. jejuni treated with organosulfur compounds. We demonstrated that bacterial injury and inactivation could be accurately investigated by complementary infrared and Raman spectroscopies using a chemical-based, “whole-organism fingerprint” with the aid of chemometrics and electron microscopy.", "title": "Investigating Antibacterial Effects of Garlic (Allium sativum) Concentrate and Garlic-Derived Organosulfur Compounds on Campylobacter jejuni by Using Fourier Transform Infrared Spectroscopy, Raman Spectroscopy, and Electron Microscopy" }, { "docid": "MED-1295", "text": "A number of polysaccharides with beta-glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1-->3)-beta-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1-->3)-beta-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the beta-D-glucan chemical structure and transforming it to a soluble form have been published. The beta-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines beta-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of beta-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.", "title": "Natural and modified (1-->3)-beta-D-glucans in health promotion and disease alleviation." }, { "docid": "MED-1185", "text": "Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Sulfite sensitivity: significance in human health." }, { "docid": "MED-5108", "text": "The effectiveness of high-temperature, short holding time (HTST) pasteurization and homogenization with respect to inactivation of Mycobacterium avium subsp. paratuberculosis was evaluated quantitatively. This allowed a detailed determination of inactivation kinetics. High concentrations of feces from cows with clinical symptoms of Johne's disease were used to contaminate raw milk in order to realistically mimic possible incidents most closely. Final M. avium subsp. paratuberculosis concentrations varying from 102 to 3.5 × 105 cells per ml raw milk were used. Heat treatments including industrial HTST were simulated on a pilot scale with 22 different time-temperature combinations, including 60 to 90°C at holding (mean residence) times of 6 to 15 s. Following 72°C and a holding time of 6 s, 70°C for 10 and 15 s, or under more stringent conditions, no viable M. avium subsp. paratuberculosis cells were recovered, resulting in >4.2- to >7.1-fold reductions, depending on the original inoculum concentrations. Inactivation kinetic modeling of 69 quantitative data points yielded an Ea of 305,635 J/mol and an lnk0 of 107.2, corresponding to a D value of 1.2 s at 72°C and a Z value of 7.7°C. Homogenization did not significantly affect the inactivation. The conclusion can be drawn that HTST pasteurization conditions equal to 15 s at ≥72°C result in a more-than-sevenfold reduction of M. avium subsp. paratuberculosis.", "title": "Effective Heat Inactivation of Mycobacterium avium subsp. paratuberculosis in Raw Milk Contaminated with Naturally Infected Feces" }, { "docid": "MED-4002", "text": "The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences (WC) >88 cm (abdominal obesity) were investigated. The randomised, double-blind, clinical trial involved 40 women aged 20-40 years. Groups received daily dietary supplements comprising 30 mL of either soy bean oil (group S; n = 20) or coconut oil (group C; n = 20) over a 12-week period, during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day. Data were collected 1 week before (T1) and 1 week after (T2) dietary intervention. Energy intake and amount of carbohydrate ingested by both groups diminished over the trial, whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged. At T1 there were no differences in biochemical or anthropometric characteristics between the groups, whereas at T2 group C presented a higher level of HDL (48.7 +/- 2.4 vs. 45.00 +/- 5.6; P = 0.01) and a lower LDL:HDL ratio (2.41 +/- 0.8 vs. 3.1 +/- 0.8; P = 0.04). Reductions in BMI were observed in both groups at T2 (P < 0.05), but only group C exhibited a reduction in WC (P = 0.005). Group S presented an increase (P < 0.05) in total cholesterol, LDL and LDL:HDL ratio, whilst HDL diminished (P = 0.03). Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity.", "title": "Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity." }, { "docid": "MED-4933", "text": "Recently, we reported on the analysis of polychlorinated biphenyls (PCBs) and chlorinated pesticides in farmed Atlantic salmon (Salmo salar) from Maine, eastern Canada, and Norway, and wild Alaskan Chinook salmon (Oncorhynchus tshawytscha). In this paper, we extend the analysis to polybrominated diphenyl ethers (PBDEs) in these samples. Total PBDE concentrations in the farmed salmon (0.4-1.4ng/g, wet weight, ww) were not significantly different from those in the wild Alaskan Chinook samples (0.4-1.2ng/g, ww), nor were significant differences found among regions. However, significant intra-regional variations in concentrations of total PBDEs and tetra-BDE 47 were observed in the salmon from the Canadian farms (p<0.01). Congener profiles were dominated by BDE-47, followed by the penta-BDEs 99 and 100. PBDE concentrations in the Canadian samples were lower than those reported two years earlier. Removal of skin resulted in no overall reduction in PBDE concentrations in our farmed salmon, and in some cases, PBDE concentrations were higher in skin-off samples. PBDEs were correlated with lipids only in the skinned samples, suggesting that there is greater accumulation and retention of PBDEs in muscle lipids than in skin-associated fat. In skin-on samples, modest correlations were observed between concentrations of PBDEs and PCBs (R(2)=0.47) and mono-ortho PCBs (R(2)=0.50), whereas PBDEs were not correlated with non-ortho PCBs.", "title": "Polybrominated diphenyl ethers (PBDEs) in farmed and wild salmon marketed in the Northeastern United States." }, { "docid": "MED-1032", "text": "To our knowledge, there is no previous clinical description in the literature of patients with defecation syncope. We evaluated 20 patients with this disorder who were a subgroup of a larger, prospective study of syncope, 13 women and seven men, with a mean age of 59 years. Eleven patients had had one episode and nine had experienced multiple episodes. Fourteen patients were recumbent before the urge to defecate, nine of these asleep. The diagnostic evaluation disclosed that two patients had gastrointestinal tract problems, three had cardiac diseases, and one had transient ischemic attacks. Three additional patients had marked orthostatic hypotension. No identifiable cause for defecation syncope was found in 11 patients, but new medical problems were noted in four of those patients. In follow-up at two years, syncope had recurred in ten patients, but the majority of recurrences were unassociated with defecation. Seven patients died during the follow-up period of underlying chronic diseases. We conclude that defecation syncope is not a single distinct clinical entity. Multiple pathologic abnormalities in association with physiologic changes during sleep and defecation may contribute to syncope. Patients with defecation syncope should undergo a careful evaluation for diagnosis of underlying illness causing syncope.", "title": "Defecation syncope. A symptom with multiple etiologies." }, { "docid": "MED-2026", "text": "OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample. METHODS: This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009-2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD). RESULTS: CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%), with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36-1.07%). CONCLUSIONS: The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.", "title": "The prevalence of celiac disease in the United States." }, { "docid": "MED-4237", "text": "OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.", "title": "Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China." }, { "docid": "MED-4957", "text": "Sarcocystis spp. are parasitic protists acquired when undercooked, cyst-laden meat is consumed. While both Sarcocystis hominis and S. cruzi encyst in beef, only S. hominis is pathogenic to humans. In this study, we used histological methods and novel molecular techniques to determine the regional prevalence and identity of Sarcocystis spp. in retail beef. Of 110 samples, 60 supported amplification of parasite rRNA by PCR. All 41 sequenced representatives were identified as S. cruzi. To compare detection methods, 48 samples were then examined in parallel by histology and PCR, and 16 and 26 samples, respectively, were positive. Five samples positive by initial histologic sections were not amplified by PCR. Fifteen PCR-positive samples did not contain sarcocysts on initial histologic section, but additional sections from these samples revealed sarcocysts in an additional 12 samples. When combined, histology with additional sections and PCR detected 31 positive specimens of the 48 total specimens. We found no evidence of human pathogen S. hominis and confirm that cattle pathogen S. cruzi is highly prevalent in this regional sample. PCR assays may increase the detection sensitivity of Sarcocystis spp. and contribute diagnostic precision.", "title": "Detection of sarcocystis parasites in retail beef: a regional survey combining histological and genetic detection methods." }, { "docid": "MED-4967", "text": "BACKGROUND: From 2003 through 2007, Vibrio cholerae serogroup O75 strains possessing the cholera toxin gene were isolated from 6 patients with severe diarrhea, including 3 in Georgia, 2 in Alabama, and 1 in South Carolina. These reports represent the first identification of V. cholerae O75 as a cause of illness in the United States. V. cholerae O75 was isolated from a water sample collected from a pond in Louisiana in 2004. Subsequently, 3 V. cholerae isolates from Louisiana (2 from patients with diarrhea in 2000 and 1 from a water sample collected in 1978) that had been previously reported as serogroup O141 were also discovered to be serogroup O75. RESULTS: All 8 patients who were infected with V. cholerae O75 were adults who became ill after consuming seafood; 2 had eaten raw oysters traced back to the Gulf Coast of the United States. All 10 isolates possessed the cholera toxin gene and were susceptible to 10 antimicrobials. One clinical isolate and 1 environmental (water) isolate had the same pulsed-field gel electrophoresis pattern; 4 clinical isolates shared a common pulsed-field gel electrophoresis pattern. CONCLUSIONS: The occurrence of these cases over many years and the concurrent identification of V. cholerae O75 in water from a Gulf Coast state suggest that these strains may survive for long periods in this environment. The patients' exposure histories suggest that infection can be acquired from consumption of raw oysters from the Gulf Coast. Clinicians and public health authorities should be vigilant for the occurrence of new toxigenic serogroups of V. cholerae that are capable of causing severe diarrhea.", "title": "Severe diarrhea caused by cholera toxin-producing vibrio cholerae serogroup O75 infections acquired in the southeastern United States." }, { "docid": "MED-1996", "text": "Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.", "title": "Childhood obesity and type 2 diabetes mellitus." }, { "docid": "MED-3987", "text": "Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.", "title": "Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis" }, { "docid": "MED-5076", "text": "The objective of the present study was to evaluate the effect of three common cooking practices (i.e., boiling, steaming, and frying) on phytochemical contents (i.e., polyphenols, carotenoids, glucosinolates, and ascorbic acid), total antioxidant capacities (TAC), as measured by three different analytical assays [Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant power (FRAP)] and physicochemical parameters of three vegetables (carrots, courgettes, and broccoli). Water-cooking treatments better preserved the antioxidant compounds, particularly carotenoids, in all vegetables analyzed and ascorbic acid in carrots and courgettes. Steamed vegetables maintained a better texture quality than boiled ones, whereas boiled vegetables showed limited discoloration. Fried vegetables showed the lowest degree of softening, even though antioxidant compounds were less retained. An overall increase of TEAC, FRAP, and TRAP values was observed in all cooked vegetables, probably because of matrix softening and increased extractability of compounds, which could be partially converted into more antioxidant chemical species. Our findings defy the notion that processed vegetables offer lower nutritional quality and also suggest that for each vegetable a cooking method would be preferred to preserve the nutritional and physicochemical qualities.", "title": "Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetables." }, { "docid": "MED-4913", "text": "Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.", "title": "Probabilistic modelling of exposure doses and implications for health risk characterization: glycoalkaloids from potatoes." }, { "docid": "MED-2520", "text": "This article discusses that the traditional analogy of an aging organism with a rusting (albeit self-repairing) car is misleading. The true analogy is a speeding car that enters a low-speed zone and damages itself because it does not and cannot slow down. For such a car without brakes (and actually without a driver), aging from rusting never occurs. Using simple analogies (although turning gerontology upside down), this article discusses the origin of aging, how overactivation of the mTOR (Target of Rapamycin) pathway causes aging, why aging causes damage (organ damage) not damage causes aging, the link between aging and age-related diseases, slow aging versus aging tolerance and suppression of aging with rapamycin.", "title": "TOR-driven aging: speeding car without brakes." }, { "docid": "MED-4789", "text": "Objectives To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design Six-month, randomized, controlled, clinical trial. Setting Veterans Affairs Puget Sound Health Care System clinical research unit. Participants Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42. Results Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. Conclusions This study provides support, using rigorous controlled methodology, for a potent nonpharma-cologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.", "title": "Effects of Aerobic Exercise on Mild Cognitive Impairment" }, { "docid": "MED-1795", "text": "Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.", "title": "Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies" }, { "docid": "MED-4714", "text": "This study investigated the association between pickled vegetable consumption and the risk of breast cancer using a validated food frequency questionnaire. A total of 358 patients with breast cancer who were matched to 360 healthy controls by age (using a 5-yr age distribution) were recruited from the National Cancer Center in South Korea. After adjusting for nondietary risk factors, total vegetable intake was inversely associated with risk of breast cancer. However, unlike nonpickled vegetables, pickled vegetable intake and its proportion relative to total vegetables were positively associated with the risk of breast cancer, and this association was more profound and consistent when pickled vegetable intake was considered as a proportion relative to total vegetables (odds ratio [OR] = 6.24, 95% confidence interval [CI] = 3.55-10.97; P for trend <0.001 for highest vs. lowest quartiles of intake) than as the absolute consumed amount (OR = 2.47, 95% CI = 1.45-4.21; P for trend = 0.015 for highest vs. lowest quartiles of intake). These results suggest that not only the amount of total vegetable intake but also the amounts of different types of vegetable (i.e., pickled or nonpickled) and their proportions relative to total vegetables are significantly associated with the risk of breast cancer.", "title": "Vegetables, but not pickled vegetables, are negatively associated with the risk of breast cancer." }, { "docid": "MED-5035", "text": "In this study, we examined the association between meat and fish intake and the risk of various cancers. Mailed questionnaires were completed by 19,732 incident, histologically confirmed cases of cancer of the stomach, colon, rectum, pancreas, lung, breast, ovary, prostate, testis, kidney, bladder, brain, non-Hodgkin's lymphomas (NHL), and leukemia and 5,039 population controls between 1994 and 1997 in 8 Canadian provinces. Measurement included information on socioeconomic status, lifestyle habits, and diet. A 69-item food frequency questionnaire provided data on eating habits 2 yr before data collection. Odds ratios and 95% confidence intervals were derived through unconditional logistic regression. Total meat and processed meat were directly related to the risk of stomach, colon, rectum, pancreas, lung, breast (mainly postmenopausal), prostate, testis, kidney, bladder, and leukemia. Red meat was significantly associated with colon, lung (mainly in men), and bladder cancer. No relation was observed for cancer of the ovary, brain, and NHL. No consistent excess risk emerged for fish and poultry, which were inversely related to the risk of a number of cancer sites. These findings add further evidence that meat, specifically red and processed meat, plays an unfavorable role in the risk of several cancers. Fish and poultry appear to be favorable diet indicators.", "title": "Meat and fish consumption and cancer in Canada." }, { "docid": "MED-1997", "text": "The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.", "title": "Vegetarian diets and childhood obesity prevention." }, { "docid": "MED-1844", "text": "Total aluminum, chromium, copper, iron, manganese, and nickel were determined in black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by electrothermal atomic absorption spectrometry after nitric/perchloric acid digestion. In each case, one ground sample of commercially available leafy material was prepared and three 0.5-g subsamples were run in parallel. The infusions were also analyzed and the percentage of each element leached into the liquor was evaluated. The obtained results indicated that hibiscus and mate contained lower levels of aluminum (272+/-19 microg/g and 369+/-22 microg/g, respectively) as referred to black tea (759+/-31 microg/g) or green tea (919micro29 microg/g) and suggested that mate drinking could be a good dietary source of essential micronutrient manganese (total content 2223+/-110 microg/g, 48.1% leached to the infusion). It was also found that the infusion of hibiscus could supply greater amounts of iron (111+/-5 microg/g total, 40.5% leached) and copper (5.9+/-0.3 microg/g total, 93.4% leached) as compared to other infusions. Moreover, it was found that the percentage of element leached to the infusion was strongly related to the tannins content in the beverage (correlation coefficients > 0.82 with the exception for nickel); for lower tannins level, better leaching was observed.", "title": "Determination of total aluminum, chromium, copper, iron, manganese, and nickel and their fractions leached to the infusions of black tea, green tea..." }, { "docid": "MED-1880", "text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)." }, { "docid": "MED-2519", "text": "To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.", "title": "Caloric restriction in humans: potential pitfalls and health concerns." }, { "docid": "MED-2476", "text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.", "title": "Diet, infection and wheezy illness: lessons from adults." }, { "docid": "MED-2374", "text": "OBJECTIVES: To assess the dose-response relationship between egg consumption and the risk of cardiovascular diseases (CVD) and diabetes. METHODS: We systematically searched MEDLINE database through December 2012. Fixed- or random-effects model was used to pool the relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses was performed to explore the potential sources of heterogeneity. Weighted linear regression model was used to estimate the dose-response relationship. RESULTS: Fourteen studies involving 320,778 subjects were included. The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02-1.38), 1.83 (95% CI 1.42-2.37), 1.68 (95% CI 1.41-2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03-1.10), 1.40 (95% CI 1.25-1.57), 1.29 (95% CI 1.21-1.37), respectively. Subgroup analyses showed that population in other western countries have increased CVD than ones in USA (RR 2.00, 95% CI 1.14 to 3.51 vs 1.13, 95% CI 0.98 to 1.30, P = 0.02 for subgroup difference). CONCLUSIONS: Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis." }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." } ]
6430	Understanding the symbols next to the Ticker	[ { "docid": "241963", "text": "\"I don't understand what the D, to the right of APPLE INC, means. This means the graph below is for the \"\"D\"\". There is selection at top and you can change this to Minutes [5,20,60,etc], Day, Week [W], Month [M] I'm not understanding how it can say BATS when in actuality AAPL is listed on the NASDAQ. Do all exchanges have info on every stock even from other exchanges and just give them to end-users at a delayed rate? BATS is an exchange. A stock can be listed on multiple exchange. I am not sure if AAPL is also listed on BATS. However looks like BATS has agreement with major stock exchanges to trade their data and supplies this to trading.com\"", "title": "" }, { "docid": "379032", "text": "BATS here means your data feed is coming from BATS only. You're not seeing up to date prices from NASDAQ, NYSE or any other of the ECNs. For a liquid equity like AAPL, BATS prices are typically up to date but for a less liquid listing, you wouldn't always see the NBBO. To get live feeds from every ECN, you have to pay. BATS is offering this information freely and that's why you're seeing it now. AAPL is listed on NASDAQ but you can trade pretty much everything on BATS, just like on other ECNs and exchanges.", "title": "" } ]	[ { "docid": "472663", "text": "\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"", "title": "" }, { "docid": "341293", "text": "\"When they entered Bankruptcy they changed their stock symbol from AAMR to AAMRQ. The Q tells investors that the company i in Bankruptcy. This i what the SEC says about the Q: \"\"Q\"\" Added To Stock Ticker Symbol When a company is involved in bankruptcy proceedings, the letter \"\"Q\"\" is added to the end of the company's stock ticker symbol. In most cases, when a company emerges from bankruptcy, the reorganization plan will cancel the existing equity stock and the old shares will be worthless. Given that risk, before purchasing stock in a bankrupt company, investors should read the company's proposed plan of reorganization. For more information about the impact of bankruptcy proceedings on securities, please read our online publication, Corporate Bankruptcy. The risks are they never recover, or that the old shares have nothing to do with new company. Many investors don't understand this. Recently some uninformed investors(?) tried to get a jump on the Twitter IPO by purchasing share of what they thought was Twitter but was instead the bankrupt company Tweeter Home Entertainment. Shares of Tweeter Home Entertainment, a Boston-based consumer electronics chain that filed for bankruptcy in 2007, soared Friday in a case of mistaken identity on Wall Street. Apparently, some investors confused Tweeter, which trades under the symbol TWTRQ, with Twitter and piled into the penny stock. Tweeter, which trades over the counter, opened at 2 cents a share and jumped as much as 15 cents — or 1,800 percent — before regulators halted trading. Almost 15 million shares had changed hands at that point, while the average daily volume is closer to 150,000. Sometimes it does happen that the new company does give some value to the old investors, but more often then not the old investors are completely wiped out.\"", "title": "" }, { "docid": "34622", "text": "There is no simple way to convert an ISIN into a stock ticker symbol. The only way to even attempt to do so is to map the ISIN to a CUSIP or SEDOL or other national identifier and then map that identifier to a stock ticker symbol.", "title": "" }, { "docid": "65618", "text": "I assume that when you say 'the DOW' that you actually mean the general market. The ticker symbol for the general market is SPY (called a 'Spider'). The ticker symbol for Nasdaq is QQQ. SPY currently pays 2.55% in dividends in a year. QQQ currently pays 1.34% in dividends in a year.", "title": "" }, { "docid": "550661", "text": "Google will be issuing Class C shares (under the ticker symbol GOOCV) to current GOOG holders in the beginning of April. The Class C shares and Class A shares will then change symbols, with the Class C shares trading under GOOG. This was announced on January 30th. Details are in this benzinga article: Projected Trading Timeline March 27 - April 2 Record Date - Payment Date Class C shares commence trading on March 27 as GOOCV on a when issued basis Class A shares continue to trade as GOOG, with entitlement to Class C shares Class A shares will also trade on an ex-distribution basis, without entitlement to the Class C shares, as GOOAV April 3 EX Date The ticker for the Class A shares will change from GOOG to GOOGL The ticker for the Class C shares will change from GOOCV to GOOG and commence regular way trading The ticker for the Class A shares that traded on an ex-distribution basis - GOOAV - will be suspended", "title": "" }, { "docid": "165973", "text": "It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.", "title": "" }, { "docid": "550648", "text": "Mortgage rates tend to track the yield on the 10-year Treasury note. The CBOE Interest Rate 10-Year T-Note, TNX, is a security directly related to this rate. Divide the CBOE price of TNX by 10 to get the yield. One can also track the 10Y T-Note yield at yahoo finance using ticker symbol (^TNX). One can also track the 10Y T-Note yield at yahoo finance using ticker symbol (^TNX).", "title": "" }, { "docid": "475984", "text": "\"Thanks for pointing out [the study](http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1748851). It's a slightly different cause than what I was describing when I posted this. Specifically, they show an effect not when the names get confused, but rather when the name similarity simply brings more attention to the stock. I was surprised nobody mentioned that in response to my post. But also interesting is that they had to control for simple confusion between stock symbols, which implies that ticker confusion has a known effect. So I dug into research on that and quickly found [this study](http://www.efmaefm.org/0EFMAMEETINGS/EFMA%20ANNUAL%20MEETINGS/2010-Aarhus/EFMA2010_0161_fullpaper.pdf) found \"\"a high positive correlation between returns on two matching stocks with similar ticker symbols\"\".\"", "title": "" }, { "docid": "350191", "text": "\"Things are in fact more complicated. It really depends what you mean by \"\"ticker\"\" and who gave you this ticker. There is several codes to identify a security: The Bloomberg code contains a code to identify the exchange as in ALU:FP the FP part refers to Euronext Paris. The RIC code works the same way but with a different convention. Exchanges are identified by the MIC code.(they are in fact divided in market segments with each market segment having a main market segment) ISIN and SEDOL codes do not provide informations about the exchange so they are usually given with a MIC. There is no guarantee that Reuters and Bloomberg won't use the same company code to refer to different company. But they usually use the exchange ticker. This ticker is requested by each company and can be anything. They are accepted most of the time. But sometimes to avoid confusion some requests are rejected. (For instance FBI ticker was refused) For more info read: The evolution of ticker symbols Financial providers like Bloomberg provides services to be informed when a security is added/removed from a market.\"", "title": "" }, { "docid": "512062", "text": "If the first one is literally a company name, then 'company name' is fine. However, companies can issue shares more than once, and those shares might be traded separately, so you could have 'Google ordinary', 'Google preference', 'Google ordinary issue B'. Seeing the name spelled out in full like this isn't as common as just the company name, but I'd normally see it referred to as 'display name'. The second one is 'symbol', 'ticker', 'ID', and others. Globally, there are many incompatible ways of referring to a stock, depending on where it's listed (companies can have dual listings, and different exchanges have different conventions), and who's referring to it (Bloomberg and Reuters have different sets of IDs, with no predictable mapping between them). So there's no one shorthand name, and the word you use depends on the context. However, 'symbol' or 'ticker' is normally fine.", "title": "" }, { "docid": "571349", "text": "I believe it’s because the old ticker machines only had 32 symbols making each symbol (1/32) a tick. (Back in the London Stock / Debt exchange in the 18th century) . The first ever government bond was issued by the Bank of England in 1693 to raise money to fund a war against France", "title": "" }, { "docid": "53993", "text": "\"A company whose stock is available for sale to the public is called a publicly-held or publicly-traded company. A public company's stock is sold on a stock exchange, and anyone with money can buy shares through a stock broker. This contrasts with a privately-held company, in which the shares are not traded on a stock exchange. In order to invest in a private company, you would need to talk directly to the current owners of the company. Finding out if a company is public or private is fairly easy. One way to check this is to look at the Wikipedia page for the company. For example, if you take a look at the Apple page, on the right sidebar you'll see \"\"Type: Public\"\", followed by the stock exchange ticker symbol \"\"AAPL\"\". Compare this to the page for Mars, Inc.; on that page, you'll see \"\"Type: Private\"\", and no stock ticker symbol listed. Another way to tell: If you can find a quote for a share price on a financial site (such as Google Finance or Yahoo Finance), you can buy the stock. You won't find a stock price for Mars, Inc. anywhere, because the stock is not publicly traded.\"", "title": "" }, { "docid": "27303", "text": "Options - yes we can :) Options tickers on Yahoo! Finance will be displayed as per new options symbology announced by OCC. The basic parts of new option symbol are: Root symbol + Expiration Year(yy)+ Expiration Month(mm)+ Expiration Day(dd) + Call/Put Indicator (C or P) + Strike price Ex.: AAPL January 19 2013, Put 615 would be AAPL130119P00615000 http://finance.yahoo.com/q?s=AAPL130119P00615000&ql=1 Futures - yes as well (: Ex.: 6A.M12.E would be 6AM12.CME using Yahoo Finance symbology. (simple as that, try it out) Get your major futures symbols from here: http://quotes.ino.com/exchanges/exchange.html?e=CME", "title": "" }, { "docid": "725", "text": "Preferred stock is traded on the market, so you can just buy it like any other. The symbol for a preferred stock is the ticker symbol followed by a dash and a letter for each class of preferred stock. Examples: Generally speaking, you should buy Preferred stock with the intention of holding onto it for at least a couple of years. Often preferred shares are lightly traded and have wide spreads that made it difficult to make money in the short term.", "title": "" }, { "docid": "397445", "text": "\"That share class may not have a ticker symbol though \"\"Black Rock MSCI ACWI ex-US Index\"\" does have a ticker for \"\"Investor A\"\" shares that is BDOAX. Some funds will have multiple share classes that is a way to have fees be applied in various ways. Mutual fund classes would be the SEC document about this if you want a government source within the US around this. Something else to consider is that if you are investing in a \"\"Fund of funds\"\" is that there can be two layers of expense ratios to consider. Vanguard is well-known for keeping its expenses low.\"", "title": "" }, { "docid": "237323", "text": "\"When we say \"\"stock market,\"\" we are usually thinking of the publicly traded stocks, such as the New York Stock Exchange or the NASDAQ. Shares of individual products do not go on these exchanges, only large corporations. You won't see a stock ticker symbol for The Force Awakens or for the iPhone 6s Plus. The reason for this is that when investors buy a stock, they are looking for something that will grow in value theoretically forever. Individual products usually have a limited lifespan. Your movie will (hopefully) generate revenue when it comes out, but after a while sales will slow down after people have seen it. If someone bought a share of stock in a movie on the stock market, they have to realize that eventually the movie will stop making money, and their share of stock won't be worth anything anymore. Instead, people invest in companies that have the potential to make new products, such as Disney or Apple. So if you were envisioning seeing the ticker symbol of your movie going across the screen on CNBC, sorry, that's not going to happen. However, you could theoretically sell shares to individual investors for a percentage of the profit. You figure out how much money you need to create the movie, and estimate how much profit you think the movie will earn. Then you find an investor (or group of investors) that is willing to give you the money you need in exchange for a percentage of the profit. Unlike a stock market investor, these investors won't be looking for the long-term growth potential of the resale value of the stock, but simply a share of the profit.\"", "title": "" }, { "docid": "94159", "text": "\"I don't have anything definitive, but in general positions in a company are not affected materially by what is called a corporate action. \"\"Corp Actions\"\" can really be anything that affects the details of a stock. Common examples are a ticker change, or exchange change, IPO (ie a new ticker), doing a split, or merging with another ticker. All of these events do not change the total value of people's positions. If a stock splits, you might have more shares, but they are worth less per share. A merger is quite similar to a split. The old company's stock is converted two the new companies stock at some ratio (ie 10 shares become 1 share) and then converted 1-to-1 to the new symbol. Shorting a stock that splits is no different. You shorted 10 shares, but after the split those are now 100 shares, when you exit the position you have to deliver back 100 \"\"new\"\" shares, though dollar-for-dollar they are the same total value. I don't see why a merger would affect your short position. The only difference is you are now shorting a different company, so when you exit the position you'll have to deliver shares of the new company back to the brokerage where you \"\"borrowed\"\" the shares you shorted.\"", "title": "" }, { "docid": "188855", "text": "\"Save the effort. For personal finance purpose, just use the simple tools. For example, if you like P&G very much but you want to diversify with ETF, use: http://etfdb.com/stock/PG/ https://www.etfchannel.com/finder/?a=etfsholding&symbol=PG Pick a ETF with highest weighting. Replace \"\"PG\"\" in the link with other tickers.\"", "title": "" }, { "docid": "104901", "text": "There's an interesting paper, Does Investor Attention Affect Stock Prices? (Sandhya et al), where researchers look at related stock tickers. When a large cap, better-known stock jumps, smaller firms with similar symbols also rise. Pretty nuts -- I interviewed the author of the paper [here](http://www.tradestreaming.com/?p=3745). There's also a transcript.", "title": "" }, { "docid": "357626", "text": "Do you use any other online features of Quicken? How many unique ticker symbols do you have? How often do you really need to update the prices? You can always continue to use Quicken, and enter the stock prices by hand. Maybe update them once a month to get an idea of how your investments are doing. That should work indefinitely.", "title": "" }, { "docid": "464957", "text": "> Indeed, the most popular of the funds, the Barclays iPath fund, known broadly by its ticker symbol VXX, has since its inception averaged a yearly return of negative 58 percent, according to FactSet. > Or look at it this way: If an investor bought VXX when it came to market in 2009 and held onto it until now, that investor would have lost 99 percent of his investment. perfect for /r/wallstreetbets !", "title": "" }, { "docid": "210470", "text": "\"Yes, there is a very good Return vs Risk graph put out at riskgrades.com. Look at it soon, because it will be unavailable after 6-30-11. The RA (return analysis) graph is what I think you are looking for. The first graph shown is an \"\"Average Return\"\", which I was told was for a 3 year period. Three period returns of 3, 6 and 12 months, are also available. You can specify the ticker symbols of funds or stocks you want a display of. For funds, the return includes price and distributions (total return), but only price movement for stocks - per site webmaster. I've used the graphs for a few years, since Forbes identified it as a \"\"Best of the Web\"\" site. Initially, I found numerous problems with some of the data and was able to work with the webmaster to correct them. Lately though, they have NOT been correcting problems that I bring to their attention. For example, try the symbols MUTHX, EDITX, AWSHX and you'll see that the Risk Grades on the graphs are seriously in error, and compress the graph results and cause overwriting and poor readability. If anyone knows of a similar product, I'd like to know about it. Thanks, George\"", "title": "" }, { "docid": "181582", "text": "\"There are two different companies named \"\"Volvo.\"\" The publicly-traded company with ticker symbol VOLV-B is called Volvo Group, or AB Volvo. They primarily build trucks, buses, and construction equipment. The company that makes the Volvo branded cars is called Volvo Cars. It is a privately-held company currently owned by the Chinese Geely Holding Group. It was all one company until 1999, when AB Volvo sold off its car brand to Ford. Because of the history, the two companies share the same logo.\"", "title": "" }, { "docid": "332244", "text": "There isn't a single universal way to reference a stock, there are 4 major identifiers with many different flavours of exchange ticker (see xkcd:Standards) I believe CUSIPs and ISINs represent a specific security rather than a specific listed instrument. This means you can have two listed instruments with one ISIN but different SEDOLs because they are listed in different places. The difference is subtle but causes problems with settlement Specifically on your question (sorry I got sidetracked) take a look at CQS Symbol convention to see what everything means", "title": "" }, { "docid": "175927", "text": "\"Use VTIVX. The \"\"Target Retirement 2045\"\" and \"\"Target Retirement 2045 Trust Plus\"\" are the same underlying fund, but the latter is offered through employers. The only differences I see are the expense ratio and the minimum investment dollars. But for the purposes of comparing funds, it should be pretty close. Here is the list of all of Vanguard's target retirement funds. Also, note that the \"\"Trust Plus\"\" hasn't been around as long, so you don't see the returns beyond the last few years. That's another reason to use plain VTIVX for comparison. See also: Why doesn't a mutual fund in my 401(k) have a ticker symbol?\"", "title": "" }, { "docid": "326858", "text": "\"There are gold index funds. I'm not sure what you mean by \"\"real gold\"\". If you mean you want to buy physical gold, you don't need to. The gold index funds will track the price of gold and will keep you from filling your basement up with gold bars. Gold index funds will buy gold and then issue shares for the gold they hold. You can then buy and sell these just like you would buy and sell any share. GLD and IAU are the ticker symbols of some of these funds. I think it is also worth pointing out that historically gold has a been a poor investment.\"", "title": "" }, { "docid": "369424", "text": "\"The official source is the most recent Form 13F that Berkshire Hathaway, which is filed with the Securities & Exchange Commission on a quarterly basis . You can find it through the SEC filing search engine, using BRKA as the ticker symbol. and then looking for the filings marked 13-FR or 13-FR/A (the \"\"/A\"\" indicates an amended filing). As you can see by looking at the 13-F filed for the quarter ending September 30 , the document isn't pretty or necessarily easy to read, hence the popularity of sites such as those that Chad linked to. It is, though, the truly official source from which websites tracking the Berkshire Hathaway portfolio derive their information.\"", "title": "" }, { "docid": "468851", "text": "Cornerstone Strategic Value Fund, Inc. is a diversified, closed-end management investment company. It was incorporated in Maryland on May 1, 1987 and commenced investment operations on June 30, 1987. The Fund’s shares of Common Stock are traded on the NYSE MKT under the ticker symbol “CLM.”[1] That essentially means that CLM is a company all of whose assets are held as tradable financial instruments OR EQUIVALENTLY CLM is an ETF that was created as a company in its own right. That it was founded in the 80s, before the modern definition of ETFs really existed, it is probably more helpful to think of it by the first definition as the website mentions that it is traded as common stock so its stock holds more in common with stock than ETFs. [1] http://www.cornerstonestrategicvaluefund.com/", "title": "" }, { "docid": "467936", "text": "For the case of spinoffs it reflects the market as activities as the specific steps that have to be followed take place. For example the spinoff of Leidos from SAIC in 2013. (I picked this one becasue I knew some of the details) On September 9, 2013, the Board of Directors of SAIC, Inc.(Ticker Symbol (NYSE):SAI) approved the following: The separation of its technical, engineering and enterprise information technology services business through the distribution of shares of SAIC Gemini, Inc. to stockholders. Each stockholder of record of SAIC, Inc. as of September 19, 2013 (Record Date) will receive one (1) share of SAIC Gemini, Inc. common stock for every seven (7) shares of SAIC, Inc. common stock held by such stockholder as of the Record Date. This distribution will be effective after market close on September 27, 2013 (Distribution Date). After the Distribution Date, SAIC Gemini, Inc. will be renamed Science Applications International Corporation (New SAIC). A one (1) for four (4) reverse stock split of the SAIC, Inc. common stock effective as of Distribution Date. After the Distribution Date, SAIC, Inc. will be renamed Leidos Holdings, Inc. (Leidos). Q 11: What are the different trading markets that may occur between Record Date and Distribution Date? A: Beginning two days prior to the Record Date of September 19, 2013 through the Distribution Date on September 27, 2013, there may be three different trading markets available with respect to SAIC, Inc. and the separation. Stock Ticker – SAI (Regular Way Trading with Due Bills): Shares of SAI common stock that trade on the regular-way market will trade with an entitlement to shares of the New SAIC common stock distributed on the Distribution Date. Purchasers in this market are purchasing both the shares of Leidos and New SAIC common stock. Form of Stock Ticker –SAIC (When Issued Trading): Shares of New SAIC common stock may be traded on a “when-issued” basis. These transactions are made conditionally because the security has been authorized, but not yet issued. Purchasers in this market are only purchasing the shares of New SAIC common stock distributed on the Distribution Date. Form of Stock Ticker – LDOS (Ex-Distribution Trading): Shares that trade on the ex-distribution market will trade without an entitlement to shares of New SAIC common stock distributed on the Distribution Date. Purchasers in this market are only purchasing the shares of Leidos common stock. So the stock price for New SAIC starts a few days before the record date of 19 September 2013, while LDOS (new name for the old SAIC) goes back much earlier. But the company didn't split until after the close of business on 27 September 2013. http://investors.saic.com/sites/saic.investorhq.businesswire.com/files/doc_library/file/GeneralStockholder-QuestionsandAnswers.pdf", "title": "" }, { "docid": "546379", "text": "Google Finance and Yahoo Finance have been transitioning their API (data interface) over the last 3 months. They are currently unreliable. If you're just interested in historical price data, I would recommend either Quandl or Tiingo (I am not affiliated with either, but I use them as data sources). Both have the same historical data (open, close, high, low, dividends, etc.) on a daily closing for thousands of Ticker symbols. Each service requires you to register and get a unique token. For basic historical data, there is no charge. I've been using both for many months and the data quality has been excellent and API (at least for python) is very easy! If you have an inclination for python software development, you can read about the drama with Google and Yahoo finance at the pandas-datareader group at https://github.com/pydata/pandas-datareader.", "title": "" } ]
196	C2 works synergistically with A-769662 to activate dephosphorylated AMPK.	[ { "docid": "19313533", "text": "The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the γ-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK α1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.", "title": "Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding." } ]	[ { "docid": "24294572", "text": "The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN.", "title": "PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K" }, { "docid": "26025820", "text": "The rat kidney ablation and infarction (A/I) model of subtotal or 5/6th nephrectomy is the most commonly studied model of nondiabetic chronic kidney disease (CKD). The A/I kidney at 1 wk exhibits reductions in kidney function, as determined by glomerular filtration rate, and diminished metabolic efficiency as determined by oxygen consumption per sodium transport (QO2/TNa). As renoprotective AMPK activity is affected by metabolic changes and cellular stress, we evaluated AMPK activity in this model system. We show that these early pathophysiological changes are accompanied by a paradoxical decrease in AMPK activity. Over time, these kidney parameters progressively worsen with extensive kidney structural, functional, metabolic, and fibrotic changes observed at 4 wk after A/I. We show that induction of AMPK activity with either metformin or 5-aminoimidazole-4-carboxamide ribonucleotide increases AMPK activity in this model and also corrects kidney metabolic inefficiency, improves kidney function, and ameliorates kidney fibrosis and structural alterations. We conclude that AMPK activity is reduced in the subtotal nephrectomy model of nondiabetic CKD, that altered regulation of AMPK is coincident with the progression of disease parameters, and that restoration of AMPK activity can suppress the progressive loss of function characteristic of this model. We propose that induction of AMPK activity may prove an effective therapeutic target for the treatment of nondiabetic CKD.", "title": "Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease." }, { "docid": "3973445", "text": "Adenosine 5′-monophosphate–activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser515 and Ser518) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser515 and Ser518 and was abolished in cells lacking AMPK catalytic subunits. Mutation of Ser515 and Ser518 abolished AMPK-mediated inhibition of JAK-STAT signaling stimulated by either the sIL-6Rα/IL-6 complex or the expression of a constitutively active V658F-mutant JAK1 in human fibrosarcoma cells. Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells. Therefore, our findings reveal a mechanism by which JAK1 function and inflammatory signaling may be suppressed in response to metabolic stress and provide a mechanistic rationale for the investigation of AMPK activators in a range of diseases associated with enhanced activation of the JAK-STAT pathway.", "title": "Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling" }, { "docid": "9899292", "text": "Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.", "title": "Role of AMP-activated protein kinase in mechanism of metformin action." }, { "docid": "9752604", "text": "In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.", "title": "Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response" }, { "docid": "3419709", "text": "Nonalcoholic fatty liver disease (NAFLD) is a growing worldwide epidemic and an important risk factor for the development of insulin resistance, type 2 diabetes, nonalcoholic steatohepatitis (NASH), and hepatic cellular carcinoma (HCC). Despite the prevalence of NAFLD, lifestyle interventions involving exercise and weight loss are the only accepted treatments for this disease. Over the last decade, numerous experimental compounds have been shown to improve NAFLD in preclinical animal models, and many of these therapeutics have been shown to increase the activity of the cellular energy sensor AMP-activated protein kinase (AMPK). Because AMPK activity is reduced by inflammation, obesity, and diabetes, increasing AMPK activity has been viewed as a viable therapeutic strategy to improve NAFLD. In this review, we propose three primary mechanisms by which AMPK activation may improve NAFLD. In addition, we examine the mechanisms by which AMPK is activated. Finally, we identify 27 studies that have used AMPK activators to reduce NAFLD. Future considerations for studies examining the relationship between AMPK and NAFLD are highlighted.", "title": "Treatment of nonalcoholic fatty liver disease: role of AMPK." }, { "docid": "49556906", "text": "Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1. Cellular metabolism regulates tissue repair and remodelling responses to injury2-4. AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5. However, the role of AMPK in fibrosis is not well understood. Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts. Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis. In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner. These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.", "title": "Metformin reverses established lung fibrosis in a bleomycin model" }, { "docid": "23974474", "text": "AMP-activated protein kinase (AMPK) is an energy-sensing enzyme whose activity is inhibited in settings of insulin resistance. Exposure to a high glucose concentration has recently been shown to increase phosphorylation of AMPK at Ser(485/491) of its α1/α2 subunit; however, the mechanism by which it does so is not known. Diacylglycerol (DAG), which is also increased in muscle exposed to high glucose, activates a number of signaling molecules including protein kinase (PK)C and PKD1. We sought to determine whether PKC or PKD1 is involved in inhibition of AMPK by causing Ser(485/491) phosphorylation in skeletal muscle cells. C2C12 myotubes were treated with the PKC/D1 activator phorbol 12-myristate 13-acetate (PMA), which acts as a DAG mimetic. This caused dose- and time-dependent increases in AMPK Ser(485/491) phosphorylation, which was associated with a ∼60% decrease in AMPKα2 activity. Expression of a phosphodefective AMPKα2 mutant (S491A) prevented the PMA-induced reduction in AMPK activity. Serine phosphorylation and inhibition of AMPK activity were partially prevented by the broad PKC inhibitor Gö6983 and fully prevented by the specific PKD1 inhibitor CRT0066101. Genetic knockdown of PKD1 also prevented Ser(485/491) phosphorylation of AMPK. Inhibition of previously identified kinases that phosphorylate AMPK at this site (Akt, S6K, and ERK) did not prevent these events. PMA treatment also caused impairments in insulin-signaling through Akt, which were prevented by PKD1 inhibition. Finally, recombinant PKD1 phosphorylated AMPKα2 at Ser(491) in cell-free conditions. These results identify PKD1 as a novel upstream kinase of AMPKα2 Ser(491) that plays a negative role in insulin signaling in muscle cells.", "title": "PKD1 Inhibits AMPKα2 through Phosphorylation of Serine 491 and Impairs Insulin Signaling in Skeletal Muscle Cells." }, { "docid": "24721866", "text": "Macrophage-derived foam cells play important roles in the progression of atherosclerosis. We reported previously that ERK1/2-dependent granulocyte/macrophage colony-stimulating factor (GM-CSF) expression, leading to p38 MAPK/ Akt signaling, is important for oxidized low density lipoprotein (Ox-LDL)-induced macrophage proliferation. Here, we investigated whether activation of AMP-activated protein kinase (AMPK) could suppress macrophage proliferation. Ox-LDL-induced proliferation of mouse peritoneal macrophages was assessed by [(3)H]thymidine incorporation and cell counting assays. The proliferation was significantly inhibited by the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and restored by dominant-negative AMPKalpha1, suggesting that AMPK activation suppressed macrophage proliferation. AICAR partially suppressed Ox-LDL-induced ERK1/2 phosphorylation and GM-CSF expression, suggesting that another mechanism is also involved in the AICAR-mediated suppression of macrophage proliferation. AICAR suppressed GM-CSF-induced macrophage proliferation without suppressing p38 MAPK/Akt signaling. GM-CSF suppressed p53 phosphorylation and expression and induced Rb phosphorylation. Overexpression of p53 or p27(kip) suppressed GM-CSF-induced macrophage proliferation. AICAR induced cell cycle arrest, increased p53 phosphorylation and expression, and suppressed GM-CSF-induced Rb phosphorylation via AMPK activation. Moreover, AICAR induced p21(cip) and p27(kip) expression via AMPK activation, and small interfering RNA (siRNA) of p21(cip) and p27(kip) restored AICAR-mediated suppression of macrophage proliferation. In conclusion, AMPK activation suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF expression and inducing cell cycle arrest. These effects of AMPK activation may represent therapeutic targets for atherosclerosis.", "title": "Activation of AMP-activated protein kinase suppresses oxidized low-density lipoprotein-induced macrophage proliferation." }, { "docid": "1590744", "text": "The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions.", "title": "AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System" }, { "docid": "3504761", "text": "The MAP kinase kinase kinase TGFβ-activated kinase 1 (TAK1) is activated by TLRs, IL-1, TNF, and TGFβ and in turn activates IKK-NF-κB and JNK, which regulate cell survival, growth, tumorigenesis, and metabolism. TAK1 signaling also upregulates AMPK activity and autophagy. Here, we investigated TAK1-dependent regulation of autophagy, lipid metabolism, and tumorigenesis in the liver. Fasted mice with hepatocyte-specific deletion of Tak1 exhibited severe hepatosteatosis with increased mTORC1 activity and suppression of autophagy compared with their WT counterparts. TAK1-deficient hepatocytes exhibited suppressed AMPK activity and autophagy in response to starvation or metformin treatment; however, ectopic activation of AMPK restored autophagy in these cells. Peroxisome proliferator-activated receptor α (PPARα) target genes and β-oxidation, which regulate hepatic lipid degradation, were also suppressed in hepatocytes lacking TAK1. Due to suppression of autophagy and β-oxidation, a high-fat diet challenge aggravated steatohepatitis in mice with hepatocyte-specific deletion of Tak1. Notably, inhibition of mTORC1 restored autophagy and PPARα target gene expression in TAK1-deficient livers, indicating that TAK1 acts upstream of mTORC1. mTORC1 inhibition also suppressed spontaneous liver fibrosis and hepatocarcinogenesis in animals with hepatocyte-specific deletion of Tak1. These data indicate that TAK1 regulates hepatic lipid metabolism and tumorigenesis via the AMPK/mTORC1 axis, affecting both autophagy and PPARα activity.", "title": "TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis." }, { "docid": "3761017", "text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.", "title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion" }, { "docid": "22036571", "text": "The AMP-activated protein kinase (AMPK) is a ubiquitous mammalian protein kinase important in the adaptation of cells to metabolic stress. The enzyme is a heterotrimer, consisting of a catalytic alpha subunit and regulatory beta and gamma subunits, each of which is a member of a larger isoform family. The enzyme is allosterically regulated by AMP and by phosphorylation of the alpha subunit. The beta subunit is post-translationally modified by myristoylation and multi-site phosphorylation. In the present study, we have examined the impact of post-translational modification of the beta-1 subunit on enzyme activity, heterotrimer assembly and subcellular localization, using site-directed mutagenesis and expression of subunits in mammalian cells. Removal of the myristoylation site (G2A mutant) results in a 4-fold activation of the enzyme and relocalization of the beta subunit from a particulate extranuclear distribution to a more homogenous cell distribution. Mutation of the serine-108 phosphorylation site to alanine is associated with enzyme inhibition, but no change in cell localization. In contrast, the phosphorylation site mutations, SS24, 25AA and S182A, while having no effects on enzyme activity, are associated with nuclear redistribution of the subunit. Taken together, these results indicate that both myristoylation and phosphorylation of the beta subunit of AMPK modulate enzyme activity and subunit cellular localization, increasing the complexity of AMPK regulation.", "title": "Post-translational modifications of the beta-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization." }, { "docid": "1686997", "text": "The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.", "title": "6-phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumor growth by inhibiting LKB1-AMPK signaling" }, { "docid": "14541844", "text": "Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Deltasnf1, Deltasnf4, and Deltasnf1Deltasnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases.", "title": "Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator" }, { "docid": "1605196", "text": "Successful generation of induced pluripotent stem cells entails a major metabolic switch from mitochondrial oxidative phosphorylation to glycolysis during the reprogramming process. The mechanism of this metabolic reprogramming, however, remains elusive. Here, our results suggest that an Atg5-independent autophagic process mediates mitochondrial clearance, a characteristic event involved in the metabolic switch. We found that blocking such autophagy, but not canonical autophagy, inhibits mitochondrial clearance, in turn, preventing iPSC induction. Furthermore, AMPK seems to be upstream of this autophagic pathway and can be targeted by small molecules to modulate mitochondrial clearance during metabolic reprogramming. Our work not only reveals that the Atg5-independent autophagy is crucial for establishing pluripotency, but it also suggests that iPSC generation and tumorigenesis share a similar metabolic switch.", "title": "Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming" }, { "docid": "4695107", "text": "The problem of antibiotic resistance, which has limited the use of cheap and old antibiotics, has necessitated the need for a continued search for new antimicrobial compounds. Understanding the mechanisms of resistance is important in the development of strategies to solving the problem. Active efflux of drugs, alteration of target sites and enzymatic degradations are the strategies by which pathogenic bacteria acquire or develop intrinsic resistance to antibiotics. Multi-drug resistance (MDR) pumps, capable of recognizing and expelling a variety of structurally unrelated compounds from the bacterial cell and conferring resistance to a wide range of antibiotics have since been characterized in many gram positive and gram negative pathogens like Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and, more recently, in mycobacteria. The ability of some chemical compounds (called MDR inhibitors or resistance modifying agents) to modify the resistance phenotype in bacteria by working synergistically with antibiotics in vitro has since been observed. The search for such compounds which can be combined with antibiotics in the treatment of drug resistant infections may be an alternative to overcoming the problem of resistance in bacteria. Crude extracts of medicinal plants stand out as veritable sources of potential resistance modifying agents and the African biosphere promises to be a potential source of such compounds owing to its rich plant species diversity.", "title": "The challenges of overcoming antibiotic resistance: Plant extracts as potential sources of antimicrobial and resistance modifying agents" }, { "docid": "38533515", "text": "The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all eukaryotic cells. The kinases are heterotrimers that comprise a catalytic subunit and regulatory subunits that sense cellular energy levels. When energy status is compromised, the system activates catabolic pathways and switches off protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. Surprisingly, recent results indicate that the AMPK system is also important in functions that go beyond the regulation of energy homeostasis, such as the maintenance of cell polarity in epithelial cells.", "title": "AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy" }, { "docid": "9021186", "text": "The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus eradication. Activation of HIV-1 gene expression in these cells together with an efficient HAART has been proposed as an adjuvant therapy aimed at decreasing the pool of latent viral reservoirs. Using the latently-infected U1 monocytic cell line and latently-infected J-Lat T-cell clones, we here demonstrated a strong synergistic activation of HIV-1 production by clinically used histone deacetylase inhibitors (HDACIs) combined with prostratin, a non-tumor-promoting nuclear factor (NF)- kappaB inducer. In J-Lat cells, we showed that this synergism was due, at least partially, to the synergistic recruitment of unresponsive cells into the expressing cell population. A combination of prostratin+HDACI synergistically activated the 5' Long Terminal Repeat (5'LTR) from HIV-1 Major group subtypes representing the most prevalent viral genetic forms, as shown by transient transfection reporter assays. Mechanistically, HDACIs increased prostratin-induced DNA-binding activity of nuclear NF-kappaB and degradation of cytoplasmic NF-kappaB inhibitor, IkappaBalpha . Moreover, the combined treatment prostratin+HDACI caused a more pronounced nucleosomal remodeling in the U1 viral promoter region than the treatments with the compounds alone. This more pronounced remodeling correlated with a synergistic reactivation of HIV-1 transcription following the combined treatment prostratin+HDACI, as demonstrated by measuring recruitment of RNA polymerase II to the 5'LTR and both initiated and elongated transcripts. The physiological relevance of the prostratin+HDACI synergism was shown in CD8(+)-depleted peripheral blood mononuclear cells from HAART-treated patients with undetectable viral load. Moreover, this combined treatment reactivated viral replication in resting CD4(+) T cells isolated from similar patients. Our results suggest that combinations of different kinds of proviral activators may have important implications for reducing the size of latent HIV-1 reservoirs in HAART-treated patients.", "title": "Synergistic Activation of HIV-1 Expression by Deacetylase Inhibitors and Prostratin: Implications for Treatment of Latent Infection" }, { "docid": "5108807", "text": "Ciliary neurotrophic factor (CNTF) induces weight loss and improves glucose tolerance in humans and rodents. CNTF is thought to act centrally by inducing hypothalamic neurogenesis to modulate food intake and peripherally by altering hepatic gene expression, in a manner similar to that of leptin. Here, we show that CNTF signals through the CNTFRα–IL-6R–gp130β receptor complex to increase fatty-acid oxidation and reduce insulin resistance in skeletal muscle by activating AMP-activated protein kinase (AMPK), independent of signaling through the brain. Thus, our findings further show that the antiobesogenic effects of CNTF in the periphery result from direct effects on skeletal muscle, and that these peripheral effects are not suppressed by diet-induced or genetic models of obesity, an essential requirement for the therapeutic treatment of obesity-related diseases.", "title": "CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK" }, { "docid": "14874811", "text": "Oxygen (O2) deprivation, or hypoxia, has profound effects on cell metabolism and growth. Cells can adapt to low O2 in part through activation of hypoxia-inducible factor (HIF). We report here that hypoxia inhibits mRNA translation by suppressing multiple key regulators, including eIF2alpha, eEF2, and the mammalian target of rapamycin (mTOR) effectors 4EBP1, p70S6K, and rpS6, independent of HIF. Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway. Hypoxic AMP-activated protein kinase (AMPK) activation also leads to eEF2 inhibition. Moreover, hypoxic effects on cellular bioenergetics and mTOR inhibition increase over time. Mutation of the TSC2 tumor suppressor gene confers a growth advantage to cells by repressing hypoxic mTOR inhibition and hypoxia-induced G1 arrest. Together, eIF2alpha, eEF2, and mTOR inhibition represent important HIF-independent mechanisms of energy conservation that promote survival under low O2 conditions.", "title": "Hypoxia-induced energy stress regulates mRNA translation and cell growth." }, { "docid": "22185730", "text": "Abnormal hyperphosphorylation of tau appears to be crucial in neurofibrillary degeneration in Alzheimer's disease (AD). Previous studies suggest that a down-regulation of protein phosphatase 2A (PP2A), the major tau phosphatase in human brain, contributes to tau hyperphosphorylation in AD. However, the effects of PP2A down-regulation on site-specific tau hyperphosphorylation is not well understood. In the present study, we showed that PP2A dephosphorylated tau at several phosphorylation sites with different efficiencies. Among the sites studied, Thr205, Thr212, Ser214, and Ser262 were the most favorable sites, and Ser199 and Ser404 were the least favorable sites for PP2A in vitro. Inhibition of PP2A with okadaic acid in metabolically active rat brain slices caused inhibition of glycogen synthase kinase-3beta (GSK-3beta) via an increase in its phosphorylation at Ser9. GSK-3beta phosphorylated tau at many sites, with Ser199, Thr205, and Ser396 being the most favorable sites in cells. The overall alterations in tau phosphorylation induced by PP2A inhibition were the result of the combined effects of both reduced tau dephosphorylation due to PP2A inhibition directly and reduced phosphorylation by GSK-3beta due to its inhibition. Because the impacts of tau phosphorylation on its biological activity and on neurofibrillary degeneration are site-specific, this study provides a new insight into the role of PP2A down-regulation in neurofibrillary degeneration in AD.", "title": "PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta." }, { "docid": "350542", "text": "BACKGROUND Pleurocidin, a 25-mer antimicrobial peptide (AMP), is known to exert bactericidal activity. However, the synergistic activity and mechanism(s) of pleurocidin in combination with conventional antibiotics, and the antibiofilm effect of the peptide are poorly understood. METHODS The interaction between pleurocidin and antibiotics was evaluated using checkerboard assay. To study the mechanism(s) involved in their synergism, we detected hydroxyl radical formation using 3'-(p-hydroxyphenyl) fluorescein, measured the NAD(+)/NADH ratio by NAD(+) cycling assay, observed change in bacterial viability with the hydroxyl radical scavenger thiourea, and investigated cytoplasmic membrane damage using propidium iodide. Also, the antibiofilm effect of pleurocidin was examined with the tissue culture plate method. RESULTS All combinations of pleurocidin and antibiotics showed synergistic interaction against bacterial strains (fractional inhibitory concentration index (FICI)≤0.5) except for Enterococcus faecium treated with a combination of the peptide and ampicillin (FICI=0.75). We identified that pleurocidin alone and in combinations with antibiotics induced formation of hydroxyl radicals. The oxidative stress was caused by a transient NADH depletion and the addition of thiourea prevented bacterial death, especially in the case of the combined treatment of pleurocidin and ampicillin showing synergisms. The combination of pleurocidin and erythromycin increased permeability of bacterial cytoplasmic membrane. Additionally, pleurocidin exhibited a potent inhibitory effect on preformed biofilm of bacterial organisms. In conclusion, pleurocidin synergized with antibiotics through hydroxyl radical formation and membrane-active mechanism, and exerted antibiofilm activity. GENERAL SIGNIFICANCE The synergistic effect between pleurocidin and antibiotics suggests the AMP is a potential therapeutic agent and adjuvant for antimicrobial chemotherapy.", "title": "Antimicrobial peptide pleurocidin synergizes with antibiotics through hydroxyl radical formation and membrane damage, and exerts antibiofilm activity." }, { "docid": "17194716", "text": "In this study, the mechanisms of actin-bundling in filopodia were examined. Analysis of cellular localization of known actin cross-linking proteins in mouse melanoma B16F1 cells revealed that fascin was specifically localized along the entire length of all filopodia, whereas other actin cross-linkers were not. RNA interference of fascin reduced the number of filopodia, and remaining filopodia had abnormal morphology with wavy and loosely bundled actin organization. Dephosphorylation of serine 39 likely determined cellular filopodia frequency. The constitutively active fascin mutant S39A increased the number and length of filopodia, whereas the inactive fascin mutant S39E reduced filopodia frequency. Fluorescence recovery after photobleaching of GFP-tagged wild-type and S39A fascin showed that dephosphorylated fascin underwent rapid cycles of association to and dissociation from actin filaments in filopodia, with t1/2 < 10 s. We propose that fascin is a key specific actin cross-linker, providing stiffness for filopodial bundles, and that its dynamic behavior allows for efficient coordination between elongation and bundling of filopodial actin filaments.", "title": "Role of fascin in filopodial protrusion" }, { "docid": "18473550", "text": "Bisphosphonates are widely used agents for the treatment of malignant bone disease. They inhibit osteoclast-mediated bone resorption and can have direct effects on cancer cells. In this study, we investigated whether the anticancer activity of the third-generation bisphosphonate zoledronic acid (ZOL) could be enhanced by combination with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). We found that ZOL and SAHA cooperated to induce cell death in the prostate cancer cell lines LNCaP and PC-3. The effect was synergistic, as evidenced by combination index isobologram analysis. ZOL and SAHA synergized to induce dissipation of the mitochondrial transmembrane potential, to activate caspase-3, and to trigger DNA fragmentation, showing that the combination of ZOL and SAHA resulted in the initiation of apoptosis. Because ZOL acts by inhibiting the mevalonate pathway, thereby preventing protein prenylation, we explored whether the mevalonate pathway was also the target of the cooperative action of ZOL and SAHA. We found that geranylgeraniol, but not farnesol, significantly reduced ZOL/SAHA-induced cell death, indicating that the synergistic action of the agents was due to the inhibition of geranylgeranylation. Consistently, a direct inhibitor of geranylgeranylation, GGTI-298, synergized with SAHA to induce cell death, whereas an inhibitor of farnesylation, FTI-277, had no effect. In addition, SAHA synergized with mevastatin, an inhibitor of the proximal enzyme in the mevalonate pathway. These in vitro findings provide a rationale for an in vivo exploration into the potential of combining SAHA and ZOL, or other inhibitors of the mevalonate pathway, as an effective strategy for anticancer therapy.", "title": "Synergistic activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid and the bisphosphonate zoledronic acid against prostate cancer cells in vitro." }, { "docid": "14328288", "text": "BACKGROUND Mammalian phosphoinositide 3-kinases (PI 3-kinases) are involved in receptor-mediated signal transduction and have been implicated in processes such as transformation and mitogenesis through their role in elevating cellular phosphatidylinositol (3,4,5)-trisphosphate. Additionally, a PI 3-kinase activity which generates phosphatidylinositol 3-phosphate has been shown to be required for protein trafficking in yeast. RESULTS We have identified a family of three distinct PI 3-kinases in Drosophila, using an approach based on the polymerase chain reaction to amplify a region corresponding to the conserved catalytic domain of PI 3-kinases. One of these family members, PI3K_92D, is closely related to the prototypical PI 3-kinase, p110 alpha; PI3K_59F is homologous to Vps34p, whereas the third, PI3K_68D, is a novel PI 3-kinase which is widely expressed throughout the Drosophila life cycle. The PI3K_68D cDNA encodes a protein of 210 kDa, which lacks sequences implicated in linking p110 PI 3-kinases to p85 adaptor proteins, but contains an amino-terminal proline-rich sequence, which could bind to SH3 domains, and a carboxy-terminal C2 domain. Biochemical analyses demonstrate that PI3K_68D has a novel substrate specificity in vitro, restricted to phosphatidylinositol and phosphatidylinositol 4-phosphate, and is unable to phosphorylate phosphatidylinositol (4,5)-bisphosphate, the implied in vivo substrate for p110. CONCLUSIONS A family of PI 3-kinases in Drosophila, including a novel class represented by PI3K_68D, is described. PI3K_68D has the potential to bind to signalling molecules containing SH3 domains, lacks p85-adaptor-binding sequences, has a Ca(2+)-independent phospholipid-binding domain and displays a restricted in vitro substrate specificity, so it could define a novel signal transduction pathway.", "title": "A family of phosphoinositide 3-kinases in Drosophila identifies a new mediator of signal transduction" }, { "docid": "6157371", "text": "Actin and its key regulatory component, cofilin, are found together in large rod-shaped assemblies in neurons subjected to energy stress. Such inclusions are also enriched in Alzheimer's disease brain, and appear in transgenic models of neurodegeneration. Neuronal insults, such as energy loss and/or oxidative stress, result in rapid dephosphorylation of the cellular cofilin pool prior to its assembly into rod-shaped inclusions. Although these events implicate a role for phosphatases in cofilin rod formation, a mechanism linking energy stress, phosphocofilin turnover, and subsequent rod assembly has been elusive. We demonstrate the ATP-sensitive interaction of the cofilin phosphatase chronophin (CIN) with the chaperone hsp90 to form a biosensor that mediates cofilin/actin rod formation. Our results suggest a model whereby attenuated interactions between CIN and hsp90 during ATP depletion enhance CIN-dependent cofilin dephosphorylation and consequent rod assembly, thereby providing a mechanism for the formation of pathological actin/cofilin aggregates during neurodegenerative energy flux.", "title": "Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation." }, { "docid": "44614949", "text": "OBJECTIVE To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. METHODS Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks. RESULTS Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL-6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP activated protein kinase (AMPK)(Thr172) phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL-6 MKO than Floxed mice on Chow. In addition, iWAT AMPK(Thr172) and hormone-sensitive lipase (HSL)(Ser565) phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH-E1α) protein content was higher (P < 0.05) in HFD ExTr IL-6 MKO than HFD ExTr Floxed mice. CONCLUSIONS These findings indicate that SkM IL-6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors.", "title": "Skeletal muscle interleukin‐6 regulates metabolic factors in iWAT during HFD and exercise training" }, { "docid": "4688340", "text": "BACKGROUND Resistance to radiotherapy continues to be a limiting factor in the treatment of cancer including head and neck squamous cell carcinoma (HNSCC). Simultaneous targeting of β1 integrin and EGFR was shown to have a higher radiosensitizing potential than mono-targeting in the majority of tested HNSCC cancer models. As tumor-initiating cells (TIC) are thought to play a key role for therapy resistance and recurrence and can be enriched in sphere forming conditions, this study investigated the efficacy of β1 integrin/EGFR targeting without and in combination with X-ray irradiation on the behavior of sphere-forming cells (SFC). METHODS HNSCC cell lines (UTSCC15, UTSCC5, Cal33, SAS) were injected subcutaneously into nude mice for tumor up-take and plated for primary and secondary sphere formation under non-adhesive conditions which is thought to reflect the enrichment of SFC and their self-renewal capacity, respectively. Treatment was accomplished by inhibitory antibodies for β1 integrin (AIIB2) and EGFR (Cetuximab) as well as X-ray irradiation (2 - 6 Gy single doses). Further, flow cytometry for TIC marker expression and cell cycling as well as Western blotting for DNA repair protein expression and phosphorylation were employed. RESULTS We found higher primary and secondary sphere forming capacity of SAS cells relative to other HNSCC cell lines, which was in line with the tumor up-take rates of SAS versus UTSCC15 cells. AIIB2 and Cetuximab administration had minor cytotoxic and no radiosensitizing effects on SFC. Intriguingly, secondary SAS spheres, representing the fraction of surviving SFC upon passaging, showed greatly enhanced radiosensitivity compared to primary spheres. Intriguingly, neither AIIB2 nor Cetuximab significantly altered basal sphere forming capacity and radiosensitivity. While an increased accumulation of G0/G1 phase cells was observable in secondary SAS spheres, DNA double strand break repair indicated no difference on the basis of significantly enhanced ATM and Chk2 dephosphorylation upon irradiation. CONCLUSIONS In the HNSCC model, sphere-forming conditions select for cells, which are unsusceptible to both anti-β1 integrin and anti-EGFR inhibitory antibodies. With regard to primary and secondary sphere formation, our data suggest that both of these SFC fractions express distinct survival strategies independent from β1 integrin and EGFR and that future work is warranted to better understand SFC survival and enrichment before and after treatment to untangle the underlying mechanisms for identifying novel, druggable cancer targets in SFC.", "title": "Efficacy of Beta1 Integrin and EGFR Targeting in Sphere-Forming Human Head and Neck Cancer Cells" }, { "docid": "14482051", "text": "BACKGROUND Panobinostat is a histone deacetylase inhibitor with antineoplastic and antiangiogenic effects in glioma that may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat combined with bevacizumab in patients with recurrent high-grade glioma (HGG). METHODS Patients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was a 6-month progression-fee survival (PFS6) rate for participants with recurrent glioblastoma (GBM). Patients with recurrent anaplastic glioma (AG) were evaluated as an exploratory arm of the study. RESULTS At interim analysis, the GBM arm did not meet criteria for continued accrual, and the GBM arm was closed. A total of 24 patients with GBM were accrued prior to closure. The PFS6 rate was 30.4% (95%, CI 12.4%-50.7%), median PFS was 5 months (range, 3-9 months), and median overall survival (OS) was 9 months (range, 6-19 months). Accrual in the AG arm continued to completion, and a total of 15 patients were enrolled. The PFS6 rate was 46.7% (range, 21%-73%), median PFS was 7 months (range, 2-10 months), and median OS was 17 months (range, 5 months-27 months). CONCLUSIONS This phase II study of panobinostat and bevacizumab in participants with recurrent GBM did not meet criteria for continued accrual, and the GBM cohort of the study was closed. Although it was reasonably well tolerated, the addition of panobinostat to bevacizumab did not significantly improve PFS6 compared with historical controls of bevacizumab monotherapy in either cohort.", "title": "Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma." } ]
481	Ethics and investment	[ { "docid": "23221", "text": "Domini offers such a fund. It might suit you, or it might include things you wish to avoid. I'm not judging your goals, but would suggest that it might be tough to find a fund that has the same values as you. If you choose individual stocks, you might have to do a lot of reading, and decide if it's all or none, i.e. if a company seems to do well, but somehow has an tiny portion in a sector you don't like, do you dismiss them? In the US, Costco, for example, is a warehouse club, and treats employees well. A fair wage, benefits, etc. But they have a liquor store at many locations. Absent the alcohol, would you research every one of their suppliers?", "title": "" }, { "docid": "523415", "text": "Avoiding tobacco, etc is fairly standard for a fund claiming ethical investing, though it varies. The hard one on your list is loans. You might want to check out Islamic mutual funds. Charging interest is against Sharia law. For example: http://www.saturna.com/amana/index.shtml From their about page: Our Funds favor companies with low price-to-earnings multiples, strong balance sheets, and proven businesses. They follow a value-oriented approach consistent with Islamic finance principles. Generally, these principles require that investors avoid interest and investments in businesses such as liquor, pornography, gambling, and banks. The Funds avoid bonds and other conventional fixed-income securities. So, it looks like it's got your list covered. (Not a recommendation, btw. I know nothing about Amana's performance.) Edit: A little more detail of their philosophy from Amana's growth fund page: Generally, Islamic principles require that investors share in profit and loss, that they receive no usury or interest, and that they do not invest in a business that is prohibited by Islamic principles. Some of the businesses not permitted are liquor, wine, casinos, pornography, insurance, gambling, pork processing, and interest-based banks or finance associations. The Growth Fund does not make any investments that pay interest. In accordance with Islamic principles, the Fund shall not purchase conventional bonds, debentures, or other interest-paying obligations of indebtedness. Islamic principles discourage speculation, and the Fund tends to hold investments for several years.", "title": "" }, { "docid": "305097", "text": "Peer to peer lending such as Kiva, Lending Club, Funding Circle(small business), SoFi(student loans), Prosper, and various other services provide you with access to the 'basic form' of investing you described in your question. Other funds: You may find the documentary '97% Owned' fascinating as it provides an overview of the monetary system of England, with parallels to US, showing only 3% of money supply is used in exchange of goods and services, 97% is engaged in some form of speculation. If speculative activities are of concern, you may need to denounce many forms of currency. Lastly, be careful of taking the term addiction too lightly and deeming something unethical too quickly. You may be surprised to learn there are many people like yourself working at 'unethical' companies changing them within.", "title": "" }, { "docid": "13013", "text": "There are a number of mutual funds which claim to be 'ethical'. Note that your definition of 'ethical' may not match theirs. This should be made clear in the prospectus of whichever mutual fund you are looking at. You will likely pay for the privilege of investing this way, in higher expenses on the mutual fund. If I may suggest another option, you may want to consider investing in low-fee mutual funds or ETFs and donating some of the profit to offset the moral issues you see.", "title": "" }, { "docid": "219977", "text": "\"Markets are amoral. If you don't buy stock in a company that has high growth/earnings, someone else will. By abstaining you will actually make it cheaper for someone else who is interested in making money. Investing in \"\"socially responsible\"\" funds will only ensure that you have less money to make a moral difference in the world when you decide to transition from working to philanthropy. Edit to clarify -- You aren't interested in buying individual stocks directly, that leaves you with two general options: You can make a statement with your investment now, or you can take the better returns and make a difference with your money later.\"", "title": "" }, { "docid": "248361", "text": "There are the Dow Jones Sustainability Indices. I believe the reports used to create them are released to the public. This could be a good place to start.", "title": "" }, { "docid": "229990", "text": "\"Are there businesses which professionally invest ethically? Yes. The common term for this is \"\"socially responsible investing\"\". Looking at that page and googling that term should provide you with plenty of pointers to funds to investigate. Of course, the definitions of \"\"ethical\"\" and \"\"socially responsible\"\" vary from person to person and fund to fund. You'll have to take a look at each fund to see which ones match your principles.\"", "title": "" } ]	[ { "docid": "332435", "text": "\"FTSE ethical investment index: http://www.ftse.com/products/indices/FTSE4Good \"\"The FTSE4Good Index is a series of ethical investment stock market indices launched in 2001 by the FTSE Group. A number of stock market indices are available, for example covering UK shares, US shares, European markets, and Japan, with inclusion based on a range of corporate social responsibility criteria. Research for the indices is supported by the Ethical Investment Research Services (EIRIS).\"\" - Wikipedia\"", "title": "" }, { "docid": "485828", "text": "To quote Adam Smith, 'Everything is worth what its purchaser will pay for it'. In this case, that means, the value of a stock is equal to the price that someone will pay for it. If you buy shares in a company, the number of people who want shares in that company has just gone up by 1. If you buy shares in companies profiting from the DAPL, you are increasing demand for those shares. You are actually making those shares more valuable, not less. If you bought all those shares, then you could simply shut the pipeline down. But that means you'd be spending billions of dollars to do so - and that money would go to the people who own the company now. The concept of 'Shareholder Activism' that you refer to, is actually more that an individual who owns a substantial number of shares (usually in the 10% ballpark) will become outspoken on the direction of the company, and attempt to elect board members who will take action to suit their liking. This is done to increase the profits of the company, so that the shareholder can make more money off of their investment. It is very expensive, and not generally done for reasons of 'ethics', unless those ethics align with a view to long-term profit (in this case, you'd need at least $1Billion to buy enough of a stake in the DAPL to make a difference). What you may instead want to consider is 'ethical investing'. This refers to the concept that you should only put your investments in companies which act ethically. For example, you could buy shares in a solar company, if you felt that was an ethical industry. In this way, you drive up demand for those types of companies, and reward the business owners who act in that fashion.", "title": "" }, { "docid": "189289", "text": "It seems ideal to have the employment be all about both income and ethics, but the problem is that for most people in the industry more often at one point or another they will have to choose between their income or their ethics. Ethics should always hold supremacy over personal gain. Because ethics maintain the relationships (formal and informal) between entities involved in the markets. Without those long term relationships, there is no room for trust and therefore no reason to be willingness for entities to exchange with one another fairly. If you don't have a overall fair financial markets, on the long term it will hurt the overall economy, why? Because people will have no trust in buying equity prices, there will be no trust in prospects. People will save most of their money in cash and outright avoid anything or everything about investing. If there are less clients, there is less capital for the entire industry. The trust of the aggregate non-active investing clients with the capital range between 100k-500 million matters. And to make it common knowledge to hold personal gain above them is not a good way to have them keep their money in the markets.", "title": "" }, { "docid": "572363", "text": "As others have said, it simply makes you a part owner. Even if you have ethical objections to a company's behavior, I'd argue that investing in it and using the proxy votes to influence the company's decisions might be even more ethical than not investing.", "title": "" }, { "docid": "203012", "text": "Banks and energy are fundamental requirements for modern civilisation, and there are plenty of both who contribute a great deal to society's well-being, but I do know where you are coming from. The nature of the system we have is that the largest organisations tend to attract the most ruthless leaders who are prepared to screw over people and the environment in pursuit of their own selfish interest. Sociopaths cunning enough to not get caught out are rewarded and those who prioritise social benefits over the growth of their organisation are out-competed and make themselves less relevant. In theory, that should be kept in check by culture of social responsibility, a strong free press and good government, but those things have been eroding for a long time. There are mutual funds who seek to invest only in ethical companies. Ethics are subjective, so there's always the possibility that you'd disagree with their choices, or they make errors of judgement, but it's a better option than a fund that only considers returns. You've got a better chance that it is run by people who think ethics are important, so they might not see their clients as muppets to be fleeced (like Goldman Sachs apparently does). Alternatively, you could invest in a fund that contributes to growing a developing nation's economy, or only invests in renewable energy, or agriculture, or whatever you consider important.", "title": "" }, { "docid": "95091", "text": "By the votes it does not. A business primary goal is to return an investment to it's shareholders which anyone can be so are they are publically traded. If you do not agree with a way a business is run ethically, do not shop not work there. They will have their work cut out for them as they compete with Amazon. Amazon distances themselves from ethical issues with sub companies and sub contractors.", "title": "" }, { "docid": "550274", "text": "If you've got the money to pay the bill today, do it. They are giving you a 25% discount if you do. You won't find an investment that will beat that. Let's look at the details of your scheme. Instead of paying $1696 today, you decide that you will pay $2261 over 60 months, or $37.68 per month. You also decide to invest $1696 today, and expect to get 6% return each year. Your investment gets you $102 each year, but you have to pay taxes on that. If you are in the 25% tax bracket, you only keep $76 (ignoring state taxes). In addition, the loan is costing you $452 in payments each year. At the end of the 5 years, you will have paid $2261 to the hospital, and your $1696 investment will be worth about $2123 after taxes. Instead, let's say that you paid the hospital $1696 today, and invested the $37.68 per month. At the end of 5 years, assuming the same 6% growth and 25% tax bracket, your investment will be worth $2552. In order for you to come out ahead by investing today and paying off the hospital over time, you would need to get at least a 17% growth on your investment. If you are ignoring taxes, then the number you need to hit is at least 13%. Conclusion: You will come out ahead by paying the hospital today, and investing the monthly payment plan that you avoided. (Note: Bankrate has a very handy investment calculator that makes it easy to calculate returns on a monthly investment.) Now, let's look at the ethics of the situation. Assume that you were able somehow to find an investment with a guaranteed return high enough to come out ahead with your plan. Should you do it? The hospital has provided you a service, and you owe the money. As a public service to people that cannot pay the bill, they allow people to pay off the bill over time at no interest. However, you are not one of these people. You have the money to pay. It is not ethical, in my opinion, to use the hospital's money to invest and try to profit.", "title": "" }, { "docid": "450662", "text": "Mary Holm, who has a column on money in the NZ Herald, had this to say on the matter: Research shows that over and over again, the top dogs in one decade can be bottom dogs the next decade, and vice versa. Past performance really is no guide to the future. ... Fees are much less likely than returns to change over time. And low fees make a big difference to the long-term growth of your account. So just how low are your fund's fees? Perhaps that means the most sensible bet would be to pick a fund with good (but not necessarily best) historical returns but also with low fees. Personally, I've also included ethics as a factor in the decision, and I chose the ethical investment option offered by Superlife, hoping that it makes a small difference as explained here. (I have no affiliation with Superlife)", "title": "" }, { "docid": "42625", "text": "\"This question drives at what value a shareholder actually provides to a corporation, and by extent, to the economy. If you subscribe for new shares (like in an Initial Public Offering), it is very straightforward to say \"\"I have provided capital to the corporation, which it is using to advance its business.\"\" If you buy shares that already exist (like in a typical share purchase on a public exchange), your money doesn't go to the company. Instead, it goes to someone who paid someone who paid someone who paid someone (etc.) who originally contributed money to the corporation. In theory, the value of a share price does not directly impact the operation of the company itself, apart from what @DanielCarson aptly noted (employee stock options are affected by share price, impacting morale, etc.). This is because in theory, the true value of a company (and thus, the value of a share) is the present value of all future cashflows (dividends + final liquidation). This means that in a technical sense, a company's share price should result from the company's value. The company's true value does not result from the share price. But what you are doing as a shareholder is impacting the liquidity available to other potential investors (also as mentioned by @DanielCarson, in reference to the desirability for future financing). The more people who invest their money in the stock market, the more liquid those stocks become. This is the true value you add to the economy by investing in stocks - you add liquidity to the market, decreasing the risk of capital investment generally. The fewer people there are who are willing to invest in a particular company, the harder it is for an investor to buy or sell shares at will. If it is difficult to sell shares in a company, the risk of holding shares in that company is higher, because you can't \"\"cash out\"\" as easily. This increased risk then does change the value of the shares - because even though the corporation's internal value is the same, the projected cashflows of the shares themselves now has a question mark around the ability to sell when desired. Whether this actually has an impact on anything depends on how many people join you in your declaration of ethical investing. Like many other forms of social activism, success relies on joint effort. This goes beyond the direct and indirect impacts mentioned above; if 'ethical investing' becomes more pronounced, it may begin to stigmatize the target companies (fewer people wanting to work for 'blacklist' corporations, fewer people buying their products, etc.).\"", "title": "" }, { "docid": "44574", "text": "\"I agree with Grade 'Eh' Bacon's answer, but there are a couple of ideas that are relevant to your particular situation: If I were you, I would invest at least half of the cash in growth ETFs because you're young enough that market variability doesn't affect you and long term growth is important. The rest should be invested in safer investments (value and dividend ETFs, bonds, cash) so that you have something to live off in the near term. You said you wanted to invest ethically. The keyword to search is \"\"socially responsible ETFs\"\". There are many, and if this is important to you, you'll have to read their prospectus to find one that matches your ethics. Since you're American, the way I understand it, you need to file taxes on income; selling stocks at a gain is income. You want to make sure that as your stocks appreciate, you sell some every year and immediately rebuy them so that you pay a small tax bill every year rather than one huge tax bill 20 years from now. Claiming about $20600 of capital gains every year would be tax free assuming you are not earning any other money. I would claim a bit more in years where you make a lot. You can mitigate your long term capital gains tax exposure by opening a Roth IRA and maxing that out. Capital gains in the Roth IRA are not taxable. Even if you don't have income from working, you can have some income if you invest in stocks that pay dividends, which would allow you to contribute to a Roth IRA. You should figure where you're going to be living because you will want to minimize the currency risk of having your money in USD while you're living abroad. If the exchange rate were to change by a lot, you might find yourself a lot poorer. There are various hedging strategies, but the easiest one is to invest some of your money in securities of the country you'll be living in. You should look into how you'll be converting money into the foreign currency. There are sometimes way of minimizing the spread when converting large amounts of money, e.g., Norbert's gambit. Shaving off 1.5% when exchanging $100k saves $1500.\"", "title": "" }, { "docid": "119401", "text": "Just because target is ultimately to blame doesn't mean the behavior is ethical. It is disappointing that so many think of ethics as anything they can get away with and avoid punishment. That isn't ethics, that is weighing risks and rewards.", "title": "" }, { "docid": "576181", "text": "\"I'd replace \"\"ethics\"\" with \"\"morality\"\" in your comment. While in many contexts ethics and morals are synonymous and used interchangeably this is a situation where the distinction is important. Ethical behaviour is adherence to a code of conduct, such as laws and regulations. Morality is about Right vs. Wrong, regardless of what's been codified.\"", "title": "" }, { "docid": "219961", "text": "Sorry, but obeying the law is ethical. You're silly symbols are wrong... you probably meant: legal != ethical Here is a thought experiment for you: So the speed limit is 60 Mph. You drive 15 Mph in that area, that is ethical driving, because there is no law governing the minimum rate of speed. It's like that... You might be an asshole for driving too slow, but you're not breaking the law. Tax is like that...", "title": "" }, { "docid": "300884", "text": "\"Well their money has to be put somewhere. And I guess the convenience and cost effectiveness of online banking and eTransfers (which is free). I'm a younger millennial, but I'm not like a \"\"bitcoin-avocado\"\" type person, so I wouldn't be able to tell you from that perspective. In terms of investments, maybe those ethical or sustainable mutual funds\"", "title": "" }, { "docid": "507777", "text": "\"I think the answer to your question is no, in theory. By screening out funds, you must actively manage the investments. To then try to ensure you track the index closely enough, you have to do further management. Either you spend your own time to do this or you pay someone else. This is ok, but it seems contrary to the primary reasons most people choose an index fund and why the product exists. You want a specific type of ethical investment(s) that has lower fees and performs well. I think you can get close, it just won't be like an \"\"index fund\"\". Don't expect equal results.\"", "title": "" }, { "docid": "193050", "text": "TIAA-Cref has their Social Choice Equity Fund, which is a Large Blend primarily equity fund that invests given the following consideration: The Fund primarily invests in companies that are screened by MSCI Inc. (“MSCI”) to favor companies that meet or exceed certain environmental, social and governance (“ESG”) criteria. The Fund does this by investing in U.S. companies included in one or more MSCI ESG Indices that meet or exceed the screening criteria described below. Prior to being eligible for inclusion in the MSCI ESG Indices, companies are subject to an ESG performance evaluation conducted by MSCI, consisting of numerous factors. The ESG evaluation process favors companies that are: (i) strong stewards of the environment; (ii) devoted to serving local communities where they operate and to human rights and philanthropy; (iii) committed to higher labor standards for their own employees and those in the supply chain; (iv) dedicated to producing high-quality and safe products; and (v) managed in an exemplary and ethical manner. https://www.tiaa.org/public/offer/products/mutual-funds/responsible-investing", "title": "" }, { "docid": "186693", "text": "I recall at the time that people on investment boards were circulating lists of companies audited by AA, as a - quite reliable - indication that they were fraudulent. I have had a lot of dealings with their offshoot AA Consulting, now known as Accenture. These dealings have not, to put it mildly, given me any reason to think that AA's culture was very ethical. And if you cannot trust an auditor, they are worthless.", "title": "" }, { "docid": "431370", "text": "From a moral perspective, this would be so great. From a marketing perspective, all it would take is to 'leak' more videos that show how industrial meat production actually looks like to turn a large number of consumers to something that's ethically better (and probably can also be argued to be healthier). Excited to see this, less from an investment perspective, but because this could really change how humans interact with animals in a significant way.", "title": "" }, { "docid": "442306", "text": "I'm not talking about the CFA, I'm talking about the entire finance industry, ethics make it all possible. Ethics provides room for trust between entities inside and outside the industry. Think about it, if you are a small cap private company wanting to go public, you trust that the underwriter will pay equity holders fairly for their units of equity. If there is no trust in the price, then there will be no underwriting, and no IPO for a new stock to enter the public markets. If there is no trust between fund managers and financial reports, the. There is no trust in estimated prospects and everything will be shriveled into speculative dangerous zones of future uncertainty. There's always a difference between being genuinely wrong and being a liar. TL;DR industry wide standards of ethics builds a foundation for trust which everyone uses directly or indirectly in finance.", "title": "" }, { "docid": "269579", "text": "You need growth in your retirement fund. Sad to say but the broad U.S. marks still has better growth perspective than the emerging markets. Look at China they are only at 6.7% growth for next year the same as this year. Russia's economy is shrinking. These are the other two super powers of 2015. The USA is still the best market to invest in historically and in the present. That's why the USA market tends to be overweight in most retirement portfolios. Now by only investing in the USA market do you miss out on trends internationally? Well you do a bit but not entirely. Many USA companies are highly international in regards to their growth. Here are some: So in short the USA market still seems to be the best growth market and you still get some international exposure. Also by investing in USA companies they sometimes are more ethical in their book keeping as opposed to some other markets. I don't think I'm the only one that is skeptical of the numbers China's government reports.", "title": "" }, { "docid": "272162", "text": "\"Shariah compliant investments attempt to achieve your \"\"ethical investing\"\" ideals. Many countries around the world have a long list of shariah compliant investments and lots of journalists will go great lengths to reveal when a company is not really shariah compliant. Standard & Poors (S&P), an American financial services company, hosts a Shariah compliant index too, but on the Toronto Stock Exchange in Canada due to the Islamaphobia rampant in the United States. But of course, international companies are indifferent to any single country's social problems, and in your new pastime as an international speculator you will get the same luxury too and exemption from the political spectrum. S&P/TSX 60 information can be found here: http://web.tmxmoney.com/tmx_indices.php?section=tsx&index=%5ETXSI Business sectors prohibited from the Shariah index include: Gambling, Pornography, Tobacco, amongst others. In the United States, the concept has been renamed \"\"B-Corporation\"\" (a play on the federal term C-Corporation and S-Corporation), and has garnered enough of a movement that several states have created these as entities people can actually register them with the state, but these are not recognized as \"\"B-Corporations\"\" to the federal government. Shariah compliant investments will be easier to find worldwide, due to the popularity of the associated religion.\"", "title": "" }, { "docid": "361783", "text": "\"Of course there can always be _some_ ways you can integrate some amounts of social responsibility into product, but I don't think that's the point he's making. Social responsibility would be called \"\"business best practice\"\" if it improved the bottom line. It is inevitable that there are times when social responsibility and business goals diverge, and at that point given two companies that are in the same market space, the one who bets against society will win. This is the sort of thing that _must_ be handled in law, and absolutely cannot be handled by allowing the free market to work because the free market will not discover ethics, it will discover that ethics don't matter in an environment that doesn't require them. It's the reason any claim that business does best when there are no regulations is absolutely false. If a company can make more by polluting and you don't have regulation that says clearly \"\"it may cost more, but we require you to compete by also being non-pollutiong\"\", then you should expect the market to converge on pollution as \"\"best practice\"\". Removing regulation won't allow business to sort this out, it will allow business to not care that they are polluting. There is the notion of a B-corp that is organized for the purpose of trying to be good guys without being sued. but it doesn't assure that they will have a fair stake int he market. It just allows them to fail without getting sued by stock holders. Basically if everyone is not required to be that level of good guy, though, B-corps are basically indulging unilateral disarmament. Sure, they can make a case that ethics matter, and that might work, but they don't need B-corp protection for that. If making the case that ethics matter was going to win in the market, any corporation could do it. For more thoughts, so I don't have to drone on here, see my articles [Fiduciary Duty vs. The Three Laws of Robotics](http://netsettlement.blogspot.com/2009/02/fiduciary-duty-vs-three-laws-of-robotics.html) and [Losing the War in a Quiet Room](http://netsettlement.blogspot.com/2012/01/losing-war-in-quiet-room.html).\"", "title": "" }, { "docid": "366847", "text": "\"private investors that don't have the time or expertise for active investment. This may be known as every private investor. An index fund ensures average returns. The bulk of active trading is done by private institutions with bucketloads of experts studying the markets and AI scraping every bit of data it can get (from the news, stock market, the weather reports, etc...). Because of that, to get above average returns an average percent of the time, singular private investors have to drastically beat the average large team of individuals/software. Now that index ETF are becoming so fashionable, could there be a tipping point at which the market signals that active investors send become so diluted that this \"\"index ETF parasitism\"\" collapses? How would this look like and would it affect only those who invest in index ETF or would it affect the stock market more generally? To make this question perhaps more on-topic: Is the fact (or presumption) that index ETF rely indirectly on active investment decisions by other market participants, as explained above, a known source of concern for personal investment? This is a well-covered topic. Some people think this will be an issue. Others point out that it is a hard issue to bootstrap. I gravitate to this view. A small active market can support a large number of passive investors. If the number of active investors ever got too low, the gains & likelihood of gains that could be made from being an active investor would rise and generate more active investors. Private investing makes sense in a few cases. One example is ethics. Some people may not want to be invested, even indirectly, in certain companies.\"", "title": "" }, { "docid": "423355", "text": "That seems unrealistic given his history of supporting corruption and ethics breaches. He was warned about corruption, ethical, and loyalty concerns for a bunch of his cabinet and he brought them on anyway. These people did not get outed by trump, they abandoned him because he is a petulent, poorly performing, and all around unstable executive. He cant even respond to domestic terrorism in any acceptable way.", "title": "" }, { "docid": "318986", "text": "\"We're not \"\"helping\"\" the company in a comparable sense to donating money to a non-profit. As you wrote, investing in a company deals with ownership and in a sense, becoming a part owner of a company, even if it is a minor ownership, indicates that we sense it has some sort of value, whether that's ethical, financial or tangible value. As investors, we should take responsibility and ensure that our voices are heard when voting occurs (sadly, not too common). EDIT: @thepassiveinvestor makes an excellent point that this paragraph only applies to IPOs: Keep in mind, when we purchase stock in a company, that money is used for business purposes. It also signals value to the market as well, if enough money or enough investors buy the stock.\"", "title": "" }, { "docid": "371747", "text": "True, that Colleges remove the lowest common denominator of ability: students who get F in classes. If you have a degree, you are probably above average in your mental abilities. But when it comes to practical knowledge, personality needed for work and in the workplace, work ethics, etc, they are not very beneficial. Actually, all those topics, practical knowledge, personality, work ethics, etc are self-taught or skills you you are born with. Cannot be taught.", "title": "" }, { "docid": "528603", "text": "\"That's not what he meant to say. He meant that beyond \"\"browsing internet\"\", you need to know math, how to write and compose long essays and reports, work ethics, business principles, and simple general knowledge... and many young millennials are terrible in math, can't write proper English, no work ethics, conviction, principal, or even aspiration to build career, let alone understand business and general knowledge. They can't even find Alaska in the map.\"", "title": "" }, { "docid": "501024", "text": "I do not think it is work ethic. I think the issue is people just do not have a choice but to do whatever their employer wants. If everyone was say rich then they could just tell their employer to F* Off. Or if the USA had a strong economic safety net then people could tell their boss to F* Off. But since the USA does not then the people are just wage slaves. I think the work ethic in other countries is more extreme than the USA but those nations people do tell their employer to get lost.", "title": "" }, { "docid": "293243", "text": "There are lots of answers here, but I'll add my two cents... The best way to win is not to play. MLM is not a viable business model. Don't go in thinking you'll beat the system by trying harder than everyone else. The only way you'll make any money is by recruiting lots of people, and selling products that can be obtained for cheaper elsewhere at a normal store. If your friend already committed to the decision and they're wise as to what's going on, yet gullible enough to try anyways, have them think about the ethics of exploiting the people down the pyramid from them. Maybe that will change their mind. All of the other answers about not investing too much of your own money remain true. You don't want to blow your life savings on a pipe dream.", "title": "" }, { "docid": "543042", "text": "Not sure you read my post based on your word choice but.... CFP is more of a marketing ploy from a consumer behavior perspective. You don't need a CFP to have the technology or knowledge to utilize what is taught in the modules and plenty of CFPs will still give shit advice. When choosing an advisor it comes down to ethics, work ethic, knowledge, experience, and fee structure in that order. Not saying to never hire a CFP, but just because somebody has a CFP doesn't mean they'll actually be any better than any other advisor.", "title": "" } ]
246	Charcoal shows no benefit for acute paraquat poisoning.	[ { "docid": "8447873", "text": "BACKGROUND Organophosphorus pesticide (OP) self-poisoning is a major problem in the developing rural world. There is little clinical trial data to guide therapy, hindering the identification of best therapy. Despite the recognition of adverse effects, gastric lavage is commonly done in Asia. We aimed to identify studies assessing its effectiveness. METHOD We systematically searched the literature for controlled clinical studies that assessed the effect of gastric lavage in OP pesticide self-poisoning. RESULTS All 56 studies identified were Chinese and reported benefit from the intervention studied, including multiple gastric lavages, use of norepinephrine or pralidoxime in the lavage fluid, concurrent treatment with naloxone or scopolamine, insertion of the gastric tube via a laparotomy incision, and lavage later than 12 h post-ingestion. However, only 23 were RCTs and none presented adequate methodology for their quality to be assessed. The patient population and study treatment protocol were not defined - large variation in case fatality in the control arm of the studies (from 4.5 to 93%) suggests marked variation between studies and likely between study arms. No study compared an intervention against a control group receiving no gastric lavage or provided any data to indicate whether a significant quantity of poison was removed. CONCLUSION Despite widespread use of multiple gastric lavages for OP pesticide poisoning across Asia, there is currently no high-quality evidence to support its clinical effectiveness. There is a need for studies to identify in which patients and for what duration gastric lavage is able to remove significant quantities of poison. Following these studies, large clinical trials will be required to address the effectiveness and safety of gastric lavage (either single or multiple) in acute OP pesticide poisoning.", "title": "Systematic review of controlled clinical trials of gastric lavage in acute organophosphorus pesticide poisoning." }, { "docid": "3430789", "text": "The present study retrospectively analyzed 19 patients diagnosed with paraquat (PQ) poisoning with the aim to investigate the effect of activated charcoal hemoperfusion on renal function and PQ elimination. The results indicated that 7 patients died and 12 survived. Non-oliguric renal failure occurred in all of the 7 patients who died. Among the 12 surviving patients, 10 had normal renal function and 2 developed non-oliguric renal failure. There was a linear correlation between plasma and urine paraquat concentration prior to and during activated charcoal hemoperfusion. The equation parameters together with the correlation coefficient on admission were as follows: Y=0.5820+1.7348X (R2=0.678; F=35.768; P<0.0001). The equation parameters together with the correlation coefficient were as follows during activated charcoal hemoperfusion: Y=0.6827+1.2649X (R2=0.626; F=50.308; P<0.0001). Therefore, it was concluded that in patients with normal renal function, the elimination kinetics of PQ by the kidneys were only associated with the plasma PQ concentration. Activated charcoal hemoperfusion had little effect on avoiding acute kidney injury in patients with severe PQ poisoning.", "title": "Effect of activated charcoal hemoperfusion on renal function in patients with paraquat poisoning." } ]	[ { "docid": "25104843", "text": "We report on a patient treated with hemoperfusion-hemodialysis (HP-HD) for severe paraquat poisoning. This procedure was adopted since the combination of adsorption and dialysis may improve overall drug removal. On admission blood paraquat was 15.8 micrograms/ml. He received conventional treatment and combined HP-HD which started within 3 hours after ingestion of the chemical and lasted 5 hours. Blood samples were obtained during and after HP-HD. The samples during HP-HD were taken before the charcoal column, between the charcoal column and the artificial kidney and after the artificial kidney. Blood clearances of paraquat were 116 +/- 32 ml/min (n=6) for the charcoal column (HP), 90 +/- 54 ml/min (n=6) for the artificial kidney (HD) and 151 +/- 37 ml/min (n=6) for the combined systems (HP-HD). After HP-HD a limited rebound of blood paraquat level was seen. One day after admission renal and hepatic failure had developed, and the patient died after 5 days. Tissue paraquat levels (microgram/g wet tissue) were: skeletal muscle 9.4, pancreas 6.0, prostate 5.6, thyroid 4.2, lungs 4.0, bone marrow 4.0, kidney 3.1, spleen 2.9, adrenal 2.9, heart 2.8, liver 2.3, stomach and testis below 1.0. Measurements of blood levels demonstrated the efficient clearances of paraquat with HP-HD from the central (plasma) compartment. However, the present results confirmed those previously reported which suggest that the efficiency of short HP-HD in treating severe paraquat poisoning is questionable since paraquat levels in the peripheral (tissue) compartment remain elevated.", "title": "Hemoperfusion-hemodialysis ineffective for paraquat removal in life-threatening poisoning?" }, { "docid": "12209494", "text": "BACKGROUND The case-fatality for intentional self-poisoning in the rural developing world is 10-50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. METHODS We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. FINDINGS Mortality did not differ between the groups. 97 (6.3%) of 1531 participants in the multiple-dose group died, compared with 105 (6.8%) of 1554 in the no charcoal group (adjusted odds ratio 0.96, 95% CI 0.70-1.33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. INTERPRETATION We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed.", "title": "Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial" }, { "docid": "22547508", "text": "Acute paraquat poisoning is often fatal. Many studies have investigated successful treatment modalities, but no standard treatment yet exists. The purpose of this study was to determine the predictors of survival after acute paraquat poisoning in 602 patients. The paraquat exposure was assessed based on the amount of ingested paraquat and a semiquantitative measure of the urine level of paraquat. Initial clinical parameters including vital signs, hemoglobin, white-blood-cell count, pH, PaCO2, PaO2, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, total bilirubin, amylase, and glucose were obtained at the time of arrival at the emergency room. Outcomes after acute paraquat poisoning were categorized as survivors and nonsurvivors. Multiple logistic regression analysis was applied to assess the predictors of survival after acute paraquat poisoning. Some patients (55.5%) survived after oral ingestion of paraquat, whereas all those exposed to paraquat percutaneous or inhalational route survived. The amount of paraquat (24.5% concentrate of 1,1'-dimethyl-4,4'-bipyridium dichloride) ingested was 45.6 +/- 74.1 mL (mean +/- SD). In addition to degree of paraquat exposure, survival after acute paraquat poisoning was associated with age, respiratory rate, pH, PaCO2, hemoglobin, white-blood-cell count, blood urea nitrogen, amylase, and the number of failed organs in multiple logistic regression analysis. In conclusion, young age, percutaneous or inhalational route, exposure to less paraquat, and lesser degrees of leukocytosis, acidosis, and renal, hepatic, and pancreatic failures on admission are good prognostic factors of survival after acute paraquat poisoning.", "title": "Predictors of survival after acute paraquat poisoning." }, { "docid": "24097933", "text": "Paraquat poisoning is characterized by multiorgan failure and pulmonary fibrosis with respiratory failure. Multiorgan failure with circulatory collapse is a major cause of early death within 3 days of paraquat ingestion. Recent studies suggested that continuous venovenous hemofiltration (CVVH) had a role in the treatment of multiorgan failure by promoting hemodynamic stability. We therefore evaluated the effect of prophylactic CVVH in 80 patients with paraquat poisoning (August 1996 to February 1999). The amount ingested was 2.1 +/- 1.0 mouthfuls (as 20% concentrate). All patients were treated with hemoperfusion (HP; duration, 6.4 +/- 3.0 hours) within 24 hours of ingestion and then randomly assigned to the HP-alone or HP-CVVH group. Forty-four patients underwent HP only, and 36 patients underwent CVVH (duration, 57.4 +/- 31.3 hours; ultrafiltration volume, 40.2 +/- 4.8 L/d) after HP. Although time to death after ingestion was significantly longer in the HP-CVVH than HP group (5.0 +/- 5.0 versus 2.5 +/- 2.1 days; P < 0.05), there was no difference in mortality rates between the two groups (66.7% versus 63.6%; P = 0.82). In the HP group, early circulatory collapse was a major cause of death compared with the HP-CVVH group, in which late respiratory failure was a major cause of death. In conclusion, prophylactic CVVH after HP prevented early death caused by circulatory collapse and prolonged survival time. However, it could not prevent late death caused by respiratory failure and did not provide a survival benefit in acute paraquat poisoning.", "title": "Failure of continuous venovenous hemofiltration to prevent death in paraquat poisoning." }, { "docid": "19132741", "text": "Paraquat, a quarternary nitrogen herbicide, is a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The mechanisms of paraquat toxicity involve: the generation of the superoxide anion, which can lead to the formation of more toxic reactive oxygen species, such as hydrogen peroxide and hydroxyl radical; and the oxidation of the cellular NADPH, the major source of reducing equivalents for the intracellular reduction of paraquat, which results in the disruption of important NADPH-requiring biochemical processes. The major cause of death in paraquat poisoning is respiratory failure due to an oxidative insult to the alveolar epithelium with subsequent obliterating fibrosis. Management of paraquat poisoning has remained mostly supportive and has been directed towards the modification of the toxicokinetics of the poison. Currently, there are no true pharmacological antagonists for paraquat and there are no chelating agents capable of binding the poison in the blood or other tissues. Recognizing the fact that paraquat induces its toxic effects via oxidative stress-mediated mechanisms, innovations in the management of paraquat poisoning are directed towards the use of antioxidants. In this review, the status of antioxidants in ameliorating or treating the toxic effects produced by paraquat is presented.", "title": "Role of antioxidants in paraquat toxicity." }, { "docid": "33203108", "text": "INTRODUCTION Paraquat is a commonly ingested poison especially in Southern India. There is no antidote for paraquat poison and consumption is often fatal. The usual cause of death is either acute lung injury or multi-organ failure. AIM To evaluate the role of early haemoperfusion as a therapy in paraquat poisoned patients. MATERIALS AND METHODS This study was a retrospective analysis of patients admitted to a Tertiary Medical College Hospital between January 2012 and December 2015 with history of paraquat consumption, comparing outcomes in those who received only gastric lavage and symptomatic treatment with those who received haemoperfusion as a therapy. The role of early haemoperfusion (≤ 6 hours) vs late haemoperfusion (> 6 hours) in paraquat poisoned patients was also compared. The data of these patients was extracted and analysed with respect to age, sex, mode of treatment, the outcome in patients who received early and late haemoperfusion. RESULTS A total of 101 patients were studied out of which 62 died. Deaths were more in those patients who received only gastric lavage with symptomatic treatment as therapy compared to those who received haemoperfusion i.e., 92.1% vs 42.9% respectively. We also found that, the survival rate was better in patients who received early haemoperfusion. CONCLUSION Early haemoperfusion was helpful in the management of severe paraquat poisoning and improved the survival rate in these patients.", "title": "Golden Hours in Severe Paraquat Poisoning-The Role of Early Haemoperfusion Therapy." }, { "docid": "40005757", "text": "Serious exposure to the herbicide paraquat usually results in death, either due to gastrointestinal caustic lesions, shock, and acute respiratory distress syndrome or related to the progressive development of pulmonary fibrosis associated with refractory hypoxemia. We report a case of suicidal paraquat ingestion in a 59-year-old man. Most of the indicators of poor prognosis were encountered in this patient. Treatment consisted of early digestive decontamination and hemodialysis, followed by antioxidant therapy, including the administration of deferoxamine (100 mg/kg in 24 h) and a continuous infusion of acetylcysteine (300 mg/kg/d during 3 weeks). The patient only developed a nonoliguric acute renal failure, a mild alteration of liver tests, and an impairment of CO transfer factor without any respiratory complaint. Renal and hepatic disturbances completely resolved within 1 month, whereas CO transfer factor remained altered 14 months later. This observation suggests that early administration of an antioxidant therapy, including deferoxamine and acetylcysteine could be usefully associated with measures that prevent digestive absorption or enhance elimination to limit systemic toxicity in potentially fatal paraquat poisoning.", "title": "Survival in a case of massive paraquat ingestion." }, { "docid": "41294031", "text": "BACKGROUND Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide. Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied. OBJECTIVES To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis. SEARCH METHODS To identify randomised controlled trials (RCTs) on this topic, we searched the Cochrane Injuries Group's Specialised Register (searched 1 February 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (Ovid SP) (1946 January Week 3 2012), EMBASE (Ovid SP) (1947 to Week 4 2012), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2012), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2012), Chinese Biomedical Literature and Retrieval System (CBM) (1978 to April 2012), Chinese Medical Current Contents (CMCC) (1995 to April 2012), and Chinese Medical Academic Conference (CMAC) (1994 to April 2012). Searches were completed on English language databases on 1 February 2012 and on Chinese language databases on 12 April 2012. SELECTION CRITERIA RCTs were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone or any other therapy in addition to standard care. DATA COLLECTION AND ANALYSIS The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effect model. MAIN RESULTS This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72; 95% CI 0.59 to 0.89). AUTHORS' CONCLUSIONS Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.", "title": "Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis." }, { "docid": "24525112", "text": "Paraquat intoxication is a fatal problem. Most paraquat intoxications happen through oral administration. We report a case of death after intravenous paraquat injection. There is little clinical data on parenteral paraquat exposure, and we describe this case and fatal progression. Toxic symptoms and severe organ function impairment developed soon after injection. Treatment with repeated activated charcoal hemoperfusion with pulse steroids, cyclophosphamide, and antioxidants was attempted. The patient died from multiple organ failure 3 days after intoxication. This case indicates that paraquat intoxication via intravenous injection, even in very small amounts, has an extremely poor prognosis.", "title": "A case of paraquat intoxication caused by intravenous injection." }, { "docid": "9976969", "text": "Psychiatric illness is a significant risk factor for both attempted and completed suicide and psychotropic medications account for 80% of all drug overdoses involving prescription medications. One challenge facing clinicians is to balance the benefit of treatment against the risk of drug overdose. The aim of the present study was to compare the age and gender distribution of patients prescribed psychotropic drugs with patients attempting and completing suicide with these drugs. Data were obtained from the Australian census and studies of general practitioner prescribing, patients who committed suicide or presented with self-poisoning within a defined geographic area. The characteristics of these populations were compared to calculate odds ratios for attempting or completing suicide with psychotropic drugs, before and after correction for rates of prescription, in different age and gender groups. The odds ratios (ORs) for self-poisoning were higher for those aged less than 45 years and yet this group was least likely to be prescribed psychotropic drugs. Men had a much higher rate of completed suicide using more lethal methods. The ORs for self-poisoning and suicide with psychotropic drugs, after correction for prescription rates, for those aged 15 to 24 years were 11.1 and 1.7, respectively. Those aged 25 to 44 years had ORs of 4.9 and 4.3, and, by contrast, those over 75 years had ORs of 0.03 and 0. Women were slightly more likely to poison themselves with psychotropic drugs (OR 1.2). However, the situation reversed after correction for prescription rates (OR 0.69). It is concluded that greater caution should be exercised in prescribing for those under 45 years of age, given their relatively higher risk of drug overdose, and that the least toxic compounds should be used. The risk (of self-poisoning) among the elderly may have been overstated, so that some patients may have been denied the benefit of adequate treatment.", "title": "An analysis of age and gender influences on the relative risk for suicide and psychotropic drug self-poisoning." }, { "docid": "80109277", "text": "© Joanna Moncrieff 2013. All rights reserved. A challenging reappraisal of the history of antipsychotics, revealing how they were transformed from neurological poisons into magical cures, their benefits exaggerated and their toxic effects minimized or ignored.", "title": "The Bitterest Pills: The Troubling Story of Antipsychotic Drugs" }, { "docid": "32450297", "text": "THE herbicide paraquat (N,N′-dimethyl 4,4′-bipyridilium) can produce widespread oedema and fibrosis in the human lung after accidental ingestion1–3. In those cases where death occurs after several weeks, there are no apparent pulmonary changes during the first few days following ingestion. Animal experiments in a variety of species have shown the lung to be the major target organ4–6. After administration of paraquat to animals, the lung has a high initial concentration and retains paraquat7–9. This retention appears to be related to the development of lung damage7 (L. L. Smith and M. S. Rose, unpublished work). The mechanism of retention of paraquat by the lung is at present not understood.", "title": "Evidence for energy-dependent accumulation of paraquat into rat lung" }, { "docid": "14361849", "text": "IntroductionWe conducted the present study to investigate the potential beneficial and adverse effects of continuous positive airway pressure (CPAP) compared with bi-level positive airway pressure (BiPAP) noninvasive ventilation in patients with cardiogenic pulmonary oedema. MethodWe included randomized controlled studies comparing CPAP and BiPAP treatment in patients with cardiogenic pulmonary oedema from the Cochrane Controlled Trials Register (2005 issue 3), and EMBASE and MEDLINE databases (1966 to 1 December 2005), without language restriction. Two reviewers reviewed the quality of the studies and independently performed data extraction. ResultsSeven randomized controlled studies, including a total of 290 patients with cardiogenic pulmonary oedema, were considered. The hospital mortality (relative risk [RR] 0.76, 95% confidence interval [CI] 0.32–1.78; P = 0.52; I2 = 0%) and risk for requiring invasive ventilation (RR 0.80, 95% CI 0.33–1.94; P = 0.62; I2 = 0%) were not significantly different between patients treated with CPAP and those treated with BiPAP. Stratifying studies that used either fixed or titrated pressure during BiPAP treatment and studies involving patients with or without hypercapnia did not change the results. The duration of noninvasive ventilation required until the pulmonary oedema resolved (weighted mean difference [WMD] in hours = 3.65, 95% CI -12.12 to +19.43; P = 0.65, I2 = 0%) and length of hospital stay (WMD in days = -0.04, 95% CI -2.57 to +2.48; P = 0.97, I2 = 0%) were also not significantly different between the two groups. Based on the limited data available, there was an insignificant trend toward an increase in new onset acute myocardial infarction in patients treated with BiPAP (RR 2.10, 95% CI 0.91–4.84; P = 0.08; I2 = 25.3%).ConclusionBiPAP does not offer any significant clinical benefits over CPAP in patients with acute cardiogenic pulmonary oedema. Until a large randomized controlled trial shows significant clinical benefit and cost-effectiveness of BiPAP versus CPAP in patients with acute cardiogenic pulmonary oedema, the choice of modality will depend mainly on the equipment available.", "title": "A comparison of continuous and bi-level positive airway pressure non-invasive ventilation in patients with acute cardiogenic pulmonary oedema: a meta-analysis" }, { "docid": "7873737", "text": "BACKGROUND Diabetes mellitus is a major risk factor for adverse outcomes after acute coronary syndromes (ACS). Because this disease may be associated with increased platelet aggregation, we investigated whether diabetic patients with ACS derive particular benefit from platelet glycoprotein (GP) IIb/IIIa receptor inhibition. METHODS AND RESULTS We performed a meta-analysis of the diabetic populations enrolled in the 6 large-scale platelet GP IIb/IIIa inhibitor ACS trials: PRISM, PRISM-PLUS, PARAGON A, PARAGON B, PURSUIT, and GUSTO IV. Among 6458 diabetic patients, platelet GP IIb/IIIa inhibition was associated with a significant mortality reduction at 30 days, from 6.2% to 4.6% (OR 0.74; 95% CI 0.59 to 0.92; P=0.007). Conversely, 23 072 nondiabetic patients had no survival benefit (3.0% versus 3.0%). The interaction between platelet GP IIb/IIIa inhibition and diabetic status was statistically significant (P=0.036). Among 1279 diabetic patients undergoing percutaneous coronary intervention (PCI) during index hospitalization, the use of these agents was associated with a mortality reduction at 30 days from 4.0% to 1.2% (OR 0.30; 95% CI 0.14 to 0.69; P=0.002). CONCLUSIONS This meta-analysis, including the entire large-scale trial experience of intravenous platelet GP IIb/IIIa inhibitors for the medical management of non-ST-segment-elevation ACS, shows that these agents may significantly reduce mortality at 30 days in diabetic patients. Although not based on a randomized assessment, the survival benefit appears to be of greater magnitude in patients undergoing PCI. Therefore, the use of platelet GP IIb/IIIa inhibitors should be strongly considered in diabetic patients with ACS.", "title": "Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes." }, { "docid": "12442311", "text": "BACKGROUND The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005-2010 compared with 1998-2004, including estimation of possible substitution effects by other analgesics. METHODS AND FINDINGS We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005-2010 compared with 1998-2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of -21 deaths (95% CI -34 to -8) per quarter, equating to approximately 500 fewer suicide deaths (-61%) over the 6 years 2005-2010, and -25 deaths (95% CI -38 to -12) per quarter, equating to 600 fewer deaths (-62%) when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed. CONCLUSIONS During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics.", "title": "Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study" }, { "docid": "29526125", "text": "BACKGROUND A major challenge for physicians is to identify patients with acute coronary syndromes who may benefit from treatment with glycoprotein-IIb/IIIa-receptor antagonists. We investigated whether troponin concentrations can be used to stratify patients for benefit from treatment with tirofiban. METHODS We enrolled 2222 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management study with coronary artery disease and who had had chest pain in the previous 24 h. All patients received aspirin and were randomly assigned treatment with tirofiban or heparin. We took baseline measurements of troponin I and troponin T. We recorded death, myocardial infarction, or recurrent ischaemia after 48 h infusion treatment and at 7 days and 30 days. FINDINGS 629 (28.3%) patients had troponin I concentrations higher than the diagnostic threshold of 1.0 microg/L and 644 (29.0%) troponin T concentrations higher than 0.1 microg/L. 30-day event rates (death, myocardial infarction) were 13.0% for troponin-I-positive patients compared with 4.9% for troponin-I-negative patients (p<0.0001), and 13.7% compared wth 3.5% for troponin T (p<0.001). At 30 days, in troponin-I-positive patients, tirofiban had lowered the risk of death (adjusted hazard ratio 0.25 [95% CI 0.09-0.68], p=0.004) and myocardial infarction (0.37 [0.16-0.84], p=0.01). This benefit was seen in medically managed patients (0.30 [0.10-0.84], p=0.004) and those undergoing revascularisation (0.37 [0.15-0.93] p=0.02) after 48 h infusion treatment. By contrast, no treatment effect was seen for troponin-I-negative patients. Similar benefits were seen for troponin-T-positive patients. INTERPRETATION Troponin I and troponin T reliably identified high-risk patients with acute coronary syndromes, managed medically and by revascularisation, who would benefit from tirofiban.", "title": "Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. PRISM Study Investigators. Platelet Receptor Inhibition in Ischemic Syndrome Management." }, { "docid": "46346525", "text": "Mu transposons carrying the chloramphenicol resistance marker have been inserted into the cloned Escherichia coli genes sodA and sodB coding for manganese superoxide dismutase (MnSOD) and iron superoxide dismutase (FeSOD) respectively, creating mutations and gene fusions. The mutated sodA or sodB genes were introduced into the bacterial chromosome by allelic exchange. The resulting mutants were shown to lack the corresponding SOD by activity measurements and immunoblot analysis. Aerobically, in rich medium, the absence of FeSOD or MnSOD had no major effect on growth or sensitivity to the superoxide generator, paraquat. In minimal medium aerobic growth was not affected, but the sensitivity to paraquat was increased, especially in the sodA mutant. A sodA sodB double mutant completely devoid of SOD was also obtained. It was able to grow aerobically in rich medium, its catalase level was unaffected and it was highly sensitive to paraquat and hydrogen peroxide; the double mutant was unable to grow aerobically on minimal glucose medium. Growth could be restored by removing oxygen, by providing an SOD-overproducing plasmid or by supplementing the medium with the 20 amino acids. It is concluded that the total absence of SOD in E. coli creates a conditional sensitivity to oxygen.", "title": "Isolation of superoxide dismutase mutants in Escherichia coli: is superoxide dismutase necessary for aerobic life?" }, { "docid": "6158879", "text": "BACKGROUND Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38. METHODS AND RESULTS We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05). CONCLUSIONS Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.", "title": "Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38." }, { "docid": "471735", "text": "Escherichia coli responds to the redox stress imposed by superoxide-generating agents such as paraquat by activating the synthesis of as many as 80 polypeptides. Expression of a key group of these inducible proteins is controlled at the transcriptional level by the soxRS locus (the soxRS regulon). A two-stage control system was hypothesized for soxRS, in which an intracellular redox signal would trigger the SoxR protein as a transcriptional activator of the soxS gene and the resulting increased levels of SoxS protein would activate transcription of the various soxRS regulon genes (B. Demple and C.F. Amábile Cuevas, Cell 67:837-839, 1990). We have constructed operon fusions of the E. coli lac genes to the soxS promoter to monitor soxS transcription. Expression from the soxS promoter is strongly inducible by paraquat in a manner strictly dependent on a functional soxR gene. Several other superoxide-generating agents also trigger soxR(+)-dependent soxS expression, and the inductions by paraquat and phenazine methosulfate were dependent on the presence of oxygen. Numerous other oxidative stress agents (H2O2, gamma rays, heat shock, etc.) failed to induce soxS, while aerobic growth of superoxide dismutase-deficient bacteria triggered soxR-dependent soxS expression. These results indicate a specific redox signal for soxS induction. A direct role for SoxR protein in the activation of the soxS gene is indicated by band-shift and DNase I footprinting experiments that demonstrate specific binding of the SoxR protein in cell extracts to the soxS promoter. The mode of SoxR binding to DNA appears to be similar to that of its homolog MerR in that the SoxR footprint spans the -10 to -35 region of the soxS promoter.", "title": "Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene." }, { "docid": "5573975", "text": "Molecules associated with the transforming growth factor β (TGF-β) superfamily, such as bone morphogenic proteins (BMPs) and TGF-β, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-β1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR-123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis.", "title": "Activin–like kinase–3 activity is important for kidney regeneration and reversal of fibrosis" }, { "docid": "6277638", "text": "The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation. Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.", "title": "Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster" }, { "docid": "39970500", "text": "PURPOSE This study assessed psychiatric medications and their potential lethality in a representative sample of suicide attempts. MATERIALS AND METHODS During 1996-98, 563 suicide attempts were studied in a general hospital in Madrid (Spain). Medication overdose was used in 456 suicide attempts (81%). The ratio between dose taken and maximum prescription dose recommended was used to evaluate the medication toxicity. RESULTS Benzodiazepines were the drugs most often used in self-poisoning (65% of overdoses), followed by new antidepressants (11%), tricyclic antidepressants (TCAs) (10%), and antipsychotics (8%). An overdose with any of the three latter psychiatric medications was significantly more frequent in patients prescribed those medications. The overdoses for TCA were potentially lethal in 47% of the cases. However, all patients who overdosed on psychiatric medications recovered well and were discharged without any sequelae. DISCUSSION This study suggests that psychiatric medications, particularly benzodiazepines, new antidepressants and antipsychotics, are relatively safe when they are used for self-poisoning. If patients with mental illnesses are under treated, there is a clear and documented higher risk for suicide. CONCLUSION It is better to prescribe psychiatric medications, particularly the new ones, rather than withhold them due to an exaggerated fear of a lethal overdose", "title": "How safe are psychiatric medications after a voluntary overdose?" }, { "docid": "18174210", "text": "BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria. METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia. In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.", "title": "Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia" }, { "docid": "36033696", "text": "OBJECTIVE The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain. METHOD All inpatients on a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a 30-minute, didactic presentation given by a medical student and a psychology student under the supervision of the primary investigator. The topics covered included the health benefits of maintaining an ideal body weight by selecting foods according to the USDA Food Pyramid, determining adequate food portions, choosing healthy meals outside the home, and beginning and adhering to an exercise program. Subjects completed a 13-item quiz concerning their knowledge of food and nutrition before and after the presentation to determine its efficacy in teaching patients the material. RESULTS Fifty patients completed both the pre- and post-presentation tests. The mean percentage of correct answers on the pre-test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of improvement was 6.1%. CONCLUSIONS This study demonstrates that psychotic individuals are able to benefit from educational presentations about nutrition and a healthy lifestyle. A statistically significant improvement in test scores suggests that subjects gained an understanding of basic concepts related to food choices and fitness.", "title": "A wellness class for inpatients with psychotic disorders." }, { "docid": "4678846", "text": "CONTEXT The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear. OBJECTIVE To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography. DESIGN AND SETTING Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong. PARTICIPANTS Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention. INTERVENTION Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent. MAIN OUTCOME MEASURES Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. RESULTS Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P =.03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 micromol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 micromol/L]; 95% CI, 1.27-1.49 mg/dL; P =.006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001). The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P =.15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events. CONCLUSION Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.", "title": "Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial." }, { "docid": "7552147", "text": "The pancreas is an organ containing two distinct populations of cells, the exocrine cells that secrete enzymes into the digestive tract, and the endocrine cells that secrete hormones into the bloodstream. It arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. Mammals, birds, reptiles and amphibians have a pancreas with similar histology and mode of development, while in some fish, the islet cells are segregated as Brockmann bodies. Invertebrates do not have a pancreas, but comparable endocrine cells may be found in the gut or the brain. The early pancreatic bud shows uniform expression of the homeobox gene IPF-1 (also known as IDX-1, STF-1 or PDX), which when mutated to inactivity leads to total absence of the organ. The occurrence of heterotopic pancreas in the embryo, and also the metaplasias that can be displayed by a regenerating pancreas in the adult, both suggest that only a few gene products distinguish the pancreatic cell state from that of the surrounding tissues of duodenum, gall bladder and liver. In the developing pancreatic buds, the endocrine cells start to differentiate before the exocrine cells, and co-expression of different hormones by the same cell is often observed at early stages. Although pancreatic endocrine cells produce many gene products also characteristic of neurons, evidence from in vitro cultures and from quailchick grafts shows that they are of endogenous and not of neural crest origin. Observational studies suggest strongly that both endocrine and exocrine cells arise from the same endodermal rudiment. Development of the pancreas in embryonic life requires a trophic stimulus from the associated mesenchyme. In postnatal life, all cell types in the pancreas continue to grow. Destruction of acinar tissue by duct ligation or ethionine treatment is followed by rapid regeneration. Surgical removal of parts of the pancreas is followed by moderate but incomplete regeneration of both acini and islets. Poisoning with alloxan or streptozotocin can lead to permanent depletion of beta cells. Although the cell kinetics of the pancreas are not understood, it seems likely that there is a continuous slow turnover of cells, fed from a stem cells population in the ducts, and that the controls on the production rate of each cell type are local rather than systemic.", "title": "Developmental biology of the pancreas." }, { "docid": "22401061", "text": "The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework-potential short-term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed.", "title": "Costs and financial feasibility of malaria elimination" }, { "docid": "32421068", "text": "Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.", "title": "Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13" }, { "docid": "46353045", "text": "Late presentation remains a major concern despite the dramatically improved prognosis realized by ART. We define a first presentation for HIV care during the course of HIV infection as 'late' if an AIDS-defining opportunistic disease is apparent, or if CD4+ T-cells are <200/microl. In the Western world, approximately 10 and 30% of HIV-infected individuals still present with CD4+ T-cells <50 and <200/microl, respectively; estimates are substantially higher for developing countries. Diagnosis and treatment of opportunistic diseases and intense supportive in-hospital care take precedence over ART. Benefits of starting ART without delay, that is, when opportunistic diseases are still active, include faster resolution of opportunistic diseases and a decreased risk of recurrence. The downside of starting ART without delay could include toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). Among asymptomatic or oligosymptomatic individuals presenting late, where ART and primary prophylaxis are initiated, approximately 10-20% will become symptomatic from drug toxicity or undiagnosed opportunistic complications, including IRIS, which require appropriate therapies. In this review we describe late presentation to HIV care, the scale of the problem, the evaluation of a late-presenting patient and challenges associated with initiation of potent antiretroviral therapy (ART) in the setting of acute opportunistic infections and other comorbidities.", "title": "Late presentation of HIV-infected individuals." }, { "docid": "26067999", "text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l", "title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement" } ]
740	MUC1-C activates the NF-κB p65 signaling pathway by interacting with IκB kinase ß.	[ { "docid": "23078022", "text": "Nuclear factor-κB (NF-κB) is constitutively activated in diverse human malignancies by mechanisms that are not understood. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and, similarly to NF-κB, blocks apoptosis and induces transformation. This study demonstrates that overexpression of MUC1 in human carcinoma cells is associated with constitutive activation of NF-κB p65. We show that MUC1 interacts with the high-molecular-weight IκB kinase (IKK) complex in vivo and that the MUC1 cytoplasmic domain binds directly to IKKβ and IKKγ. Interaction of MUC1 with both IKKβ and IKKγ is necessary for IKKβ activation, resulting in phosphorylation and degradation of IκBα. Studies in non-malignant epithelial cells show that MUC1 is recruited to the TNF-R1 complex and interacts with IKKβ–IKKγ in response to TNFα stimulation. TNFα-induced recruitment of MUC1 is dependent on TRADD and TRAF2, but not the death-domain kinase RIP1. In addition, MUC1-mediated activation of IKKβ is dependent on TAK1 and TAB2. These findings indicate that MUC1 is important for physiological activation of IKKβ and that overexpression of MUC1, as found in human cancers, confers sustained induction of the IKKβ–NF-κB p65 pathway.", "title": "MUC1 oncoprotein activates the IκB kinase β complex and constitutive NF-κB signalling" } ]	[ { "docid": "83308790", "text": "In mammals, the canonical nuclear factor κB (NF-κB) signaling pathway activated in response to infections is based on degradation of IκB inhibitors. This pathway depends on the IκB kinase (IKK), which contains two catalytic subunits, IKKα and IKKβ. IKKβ is essential for inducible IκB phosphorylation and degradation, whereas IKKα is not. Here we show that IKKα is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-κB target genes, and processing of the NF-κB2 (p100) precursor. IKKα preferentially phosphorylates NF-κB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-κB–inducing kinase (NIK). IKKα is therefore a pivotal component of a second NF-κB activation pathway based on regulated NF-κB2 processing rather than IκB degradation.", "title": "Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway" }, { "docid": "27093166", "text": "BACKGROUND Ketamine, as an anesthetic agent, has an anti-inflammatory effect. In the present study, we investigated whether ketamine inhibits release of high mobility group box 1 (HMGB1), a late-phase cytokine of sepsis, in lipopolysaccharide (LPS)-stimulated macrophages through heme oxygenase-1 (HO-1) induction. METHODS Macrophages were preincubated with various concentrations of ketamine and then treated with LPS (1 μg/mL). The cell culture supernatants were collected to measure inflammatory mediators (HMGB1, nitric oxide, tumor necrosis factor-α, and interleukin 1β) by enzyme-linked immunosorbent assay. Moreover, HO-1 protein expression, the phosphorylation and degradation of IκB-α, and the nuclear translocation of nuclear factor E2-related factor 2 and nuclear factor κB (NF-κB) p65 were tested by Western blot analysis. In addition, to further identify the role of HO-1 in this process, tin protoporphyrin (SnPP), an HO-1 inhibitor, was used. RESULTS Ketamine treatment dose-dependently attenuated the increased levels of proinflammatory mediators (HMGB1, nitric oxide, tumor necrosis factor α, and interleukin 1β) and increased the HO-1 protein expression in LPS-activated macrophages. Furthermore, ketamine suppressed the phosphorylation and degradation of IκB-α as well as the LPS-stimulated nuclear translocation of NF-κB p65 in macrophages. In addition, the present study also demonstrated that ketamine induced HO-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 in macrophages. The effects of ketamine on LPS-induced proinflammatory cytokines production were partially reversed by the HO inhibitor tin protoporphyrin (SnPP). CONCLUSION Ketamine inhibits the release of HMGB1 in LPS-stimulated macrophages, and this effect is at least partly mediated by the activation of the Nrf2/HO-1 pathway and NF-κB suppression.", "title": "Ketamine reduces LPS-induced HMGB1 via activation of the Nrf2/HO-1 pathway and NF-κB suppression." }, { "docid": "39424916", "text": "Wedelolactone is a major coumarin of Eclipta prostrata, which is used for preventing liver damage. However the effects of wedelolactone on hepatic fibrosis remained unexplored. The purpose of this study was to demonstrate the anti-fibrotic effects of wedelolactone on activated human hepatic stellate cell (HSC) line LX-2 and the possible underlying mechanisms by means of MTT assay, Hoechst staining, as well as real-time quantitative PCR and western blot. The results showed that wedelolactone reduced the cellular viability of LX-2 in a time and dose-dependent manner. After treatment of wedelolactone, the expressions of collagen I and α-smooth muscle actin, two biomarkers of LX-2 activation, were remarkably decreased. The apoptosis of LX-2 cells was induced by wedelolactone accompanied with the decreasing expression of anti-apoptotic Bcl-2 and increasing expression of pro-apoptotic Bax. In addition, phosphorylated status of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was up-regulated, but not in p38. Moreover, wedelolactone significantly repressed the level of phosphorylated inhibitor of nuclear factor κB (IκB) and p65 in nucleus in spite of tumor necrosis factor-α stimulation. In conclusion, wedelolactone could significantly inhibit the activation of LX-2 cells, the underlying mechanisms of which included inducing Bcl-2 family involved apoptosis, up-regulating phosphorylated status of ERK and JNK expressions, and inhibiting nuclear factor-κB (NF-κB) mediated activity. Wedelolactone might present as a useful tool for the prevention and treatment of hepatic fibrosis.", "title": "Wedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2." }, { "docid": "23737024", "text": "Two studies were performed to investigate the effects of an acute bout of physical exercise on the nuclear protein kappaB (NF-kappaB) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n=6) was run on the treadmill at 25 m/min, 5% grade, for 1 h or until exhaustion (Ex), and compared with a second group (n=6) injected with two doses of pyrrolidine dithiocarbamate (PDTC, 100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional groups of rats (n=6) were injected with either 8 mg/kg (i.p.) of lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline (C) and killed at resting condition. Ex rats showed higher levels of NF-kappaB binding and P50 protein content in muscle nuclear extracts compared with C rats. Cytosolic IkappaBalpha and IkappaB kinase (IKK) contents were decreased, whereas phospho-IkappaBalpha and phospho-IKK contents were increased, comparing Ex vs. C. The exercise-induced activation of NF-kappaB signaling cascade was partially abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and exaggerated the effects observed in Ex rats. In Study 2, the time course of exercise-induced NF-kappaB activation was examined. Highest levels of NF-kappaB binding were observed at 2 h postexercise. Decreased cytosolic IkappaBalpha and increased phosphor-IkappaBalpha content were found 0-1 h postexercise whereas P65 reached peak levels at 2-4 h. These data suggest that the NF-kappaB signaling pathway can be activated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant production. The cascade of intracellular events may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier (Pfluegers Arch. 442, 426-434, 2001).", "title": "Acute exercise activates nuclear factor (NF)-kappaB signaling pathway in rat skeletal muscle." }, { "docid": "41913714", "text": "Digitoxin and structurally related cardiac glycoside drugs potently block activation of the TNF-α/NF-κB signaling pathway. We have hypothesized that the mechanism might be discovered by searching systematically for selective inhibitory action through the entire pathway. We report that the common action of these drugs is to block the TNF-α-dependent binding of TNF receptor 1 to TNF receptor-associated death domain. This drug action can be observed with native cells, such as HeLa, and reconstituted systems prepared in HEK293 cells. All other antiinflammatory effects of digitoxin on NF-κB and c-Jun N-terminal kinase pathways appear to follow from the blockade of this initial upstream signaling event.", "title": "Cardiac glycosides inhibit TNF-α/NF-κB signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor" }, { "docid": "9956893", "text": "OBJECTIVE Advances made in the past ten years highlight the notion that peroxisome proliferator-activated receptors gamma (PPARγ) has protective properties in the pathophysiology of osteoarthritis (OA). The aim of this study was to define the roles of PPARγ in AGEs-induced inflammatory response in human chondrocytes. METHODS Primary human chondrocytes were stimulated with AGEs in the presence or absence of neutralizing antibody against RAGE (anti-RAGE), MAPK specific inhibitors and PPARγ agonist pioglitazone. The expression of IL-1, MMP-13, TNF-α, PPARγ, nuclear NF-κB p65 and cytosol IκBα was determined by western blotting and real-time PCR. RESULTS AGEs could enhance the expression of IL-1, TNF-α, and MMP-13, but the level of PPARγ was decreased in a time- and dose-dependent manner, which was inhibited by anti-RAGE, SB203580 (P38 MAPK specific inhibitor) and SP600125 (a selective inhibitor of JNK). PPARγ agonist pioglitazone could inhibit the effects of AGEs-induced inflammatory response and PPARγ down-regulation. In human chondrocytes, AGEs could induce cytosol IκBα degradation and increase the level of nuclear NF-κB p65, which was inhibited by PPARγ agonist pioglitazone. CONCLUSIONS In primary human chondrocytes, AGEs could down-regulate PPARγ expression and increase the inflammatory mediators, which could be reversed by PPARγ agonist pioglitazone. Activation of RAGE by AGEs triggers a cascade of downstream signaling, including MAPK JNK/ p38, PPARγ and NF-κB. Taken together, PPARγ could be a potential target for pharmacologic intervention in the treatment of OA.", "title": "The Role of PPARγ in Advanced Glycation End Products-Induced Inflammatory Response in Human Chondrocytes" }, { "docid": "364522", "text": "OBJECTIVES Calcific aortic valve (AV) disease is known to be an inflammation-related process. High-mobility group box-1 (HMGB1) protein and Toll-like receptor 4 (TLR4) have been reported to participate in several inflammatory diseases. The purpose of the present study was to determine whether the HMGB1-TLR4 axis is involved in calcific AV disease, and to evaluate the effect of HMGB1, and its potential mechanisms, on the pro-osteogenic phenotype change of valvular interstitial cells (VICs). METHODS Expression of HMGB1 and TLR4 in human calcific AVs was evaluated using immunohistochemical staining and immunoblotting. Cultured VICs were used as an in vitro model. The VICs were stimulated with HMGB1 for analysis, with versus without TLR4 small interfering ribonucleic acid (siRNA), c-Jun N-terminal kinase mitogen-activated protein kinase (JNK MAPK), and nuclear factor kappa-B (NF-κB) inhibitors. RESULTS Enhanced accumulation of HMGB1 and TLR4 was observed in calcific valves. Moreover, we found that HMGB1 induced high levels of pro-inflammatory cytokine production and promoted the osteoblastic differentiation and calcification of VICs. In addition, HMGB1 induced phosphorylation of JNK MAPK and NF-κB. However, these effects were markedly suppressed by siRNA silencing of TLR4. In addition, blockade of JNK MAPK and NF-κB phosphorylation prohibited HMGB1-induced production of pro-osteogenic factors, and mineralization of VICs. CONCLUSIONS The HMGB1 protein may promote osteoblastic differentiation and calcification of VICs, through the TLR4-JNK-NF-κB signaling pathway.", "title": "High-mobility group box-1 protein induces osteogenic phenotype changes in aortic valve interstitial cells." }, { "docid": "18956141", "text": "Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.", "title": "NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions" }, { "docid": "1044552", "text": "Proteinase-activated receptors (PARs) belong to a family of G protein-coupled receptors. PARs are activated by a serine-dependent cleavage generating a tethered activating ligand. PAR-2 was shown to be involved in inflammatory pathways. We investigated the in situ levels and modulation of PAR-2 in human normal and osteoarthritis (OA) cartilage/chondrocytes. Furthermore, we evaluated the role of PAR-2 on the synthesis of the major catabolic factors in OA cartilage, including metalloproteinase (MMP)-1 and MMP-13 and the inflammatory mediator cyclooxygenase 2 (COX-2), as well as the PAR-2-activated signalling pathways in OA chondrocytes. PAR-2 expression was determined using real-time reverse transcription-polymerase chain reaction and protein levels by immunohistochemistry in normal and OA cartilage. Protein modulation was investigated in OA cartilage explants treated with a specific PAR-2-activating peptide (PAR-2-AP), SLIGKV-NH2 (1 to 400 μM), interleukin 1 beta (IL-1β) (100 pg/mL), tumor necrosis factor-alpha (TNF-α) (5 ng/mL), transforming growth factor-beta-1 (TGF-β1) (10 ng/mL), or the signalling pathway inhibitors of p38 (SB202190), MEK1/2 (mitogen-activated protein kinase kinase) (PD98059), and nuclear factor-kappa B (NF-κB) (SN50), and PAR-2 levels were determined by immunohistochemistry. Signalling pathways were analyzed on OA chondrocytes by Western blot using specific phospho-antibodies against extracellular signal-regulated kinase 1/2 (Erk1/2), p38, JNK (c-jun N-terminal kinase), and NF-κB in the presence or absence of the PAR-2-AP and/or IL-1β. PAR-2-induced MMP and COX-2 levels in cartilage were determined by immunohistochemistry. PAR-2 is produced by human chondrocytes and is significantly upregulated in OA compared with normal chondrocytes (p < 0.04 and p < 0.03, respectively). The receptor levels were significantly upregulated by IL-1β (p < 0.006) and TNF-α (p < 0.002) as well as by the PAR-2-AP at 10, 100, and 400 μM (p < 0.02) and were downregulated by the inhibition of p38. After 48 hours of incubation, PAR-2 activation significantly induced MMP-1 and COX-2 starting at 10 μM (both p < 0.005) and MMP-13 at 100 μM (p < 0.02) as well as the phosphorylation of Erk1/2 and p38 within 5 minutes of incubation (p < 0.03). Though not statistically significant, IL-1β produced an additional effect on the activation of Erk1/2 and p38. This study documents, for the first time, functional consequences of PAR-2 activation in human OA cartilage, identifies p38 as the major signalling pathway regulating its synthesis, and demonstrates that specific PAR-2 activation induces Erk1/2 and p38 in OA chondrocytes. These results suggest PAR-2 as a potential new therapeutic target for the treatment of OA.", "title": "Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study" }, { "docid": "6690087", "text": "We addressed the regulatory function of mammalian target of rapamycin (mTOR) in the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. Pretreatment of HUVECs with rapamycin, an inhibitor of mTOR, augmented thrombin-induced ICAM-1 expression. Inhibition of mTOR by this approach promoted whereas over-expression of mTOR inhibited thrombin-induced transcriptional activity of NF-kappaB, an essential regulator of ICAM-1 transcription. Analysis of the NF-kappaB signaling pathway revealed that inhibition of mTOR potentiated IkappaB kinase activation resulting in a rapid and persistent phosphorylation of IkappaBalpha on Ser32 and Ser36, a requirement for IkappaBalpha degradation. Consistent with these data, we observed a more efficient and stable nuclear localization of RelA/p65 and, subsequently, the DNA binding activity of NF-kappaB by thrombin following mTOR inhibition. These data define a novel role of mTOR in down-regulating thrombin-induced ICAM-1 expression in endothelial cells by controlling a delayed and transient activation of NF-kappaB.", "title": "Inhibition of mammalian target of rapamycin potentiates thrombin-induced intercellular adhesion molecule-1 expression by accelerating and stabilizing NF-kappa B activation in endothelial cells." }, { "docid": "52925737", "text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.", "title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration" }, { "docid": "52873726", "text": "The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer. The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD). The current paradigm for regulation of this pathway centres on phosphorylation-dependent nucleocytoplasmic shuttling of YAP/TAZ through a complex network of upstream components. However, unlike other transcription factors, such as SMAD, NF-κB, NFAT and STAT, the regulation of TEAD nucleocytoplasmic shuttling has been largely overlooked. In the present study, we show that environmental stress promotes TEAD cytoplasmic translocation via p38 MAPK in a Hippo-independent manner. Importantly, stress-induced TEAD inhibition predominates YAP-activating signals and selectively suppresses YAP-driven cancer cell growth. Our data reveal a mechanism governing TEAD nucleocytoplasmic shuttling and show that TEAD localization is a critical determinant of Hippo signalling output.", "title": "Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation" }, { "docid": "22210434", "text": "The kinase TAK1 is critical for innate and B cell immunity. The function of TAK1 in T cells is unclear, however. We show here that T cell–specific deletion of the gene encoding TAK1 resulted in reduced development of thymocytes, especially of regulatory T cells expressing the transcription factor Foxp3. In mature thymocytes, TAK1 was required for interleukin 7–mediated survival and T cell receptor–dependent activation of transcription factor NF-κB and the kinase Jnk. In effector T cells, TAK1 was dispensable for T cell receptor–dependent NF-κB activation and cytokine production, but was important for proliferation and activation of the kinase p38 in response to interleukins 2, 7 and 15. Thus, TAK1 is essential for the integration of T cell receptor and cytokine signals to regulate the development, survival and function of T cells.", "title": "The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function" }, { "docid": "6936141", "text": "The HIV-1 protein Nef enhances viral pathogenicity and accelerates disease progression in vivo. Nef potentiates T cell activation by an unknown mechanism, probably by optimizing the intracellular environment for HIV replication. Using a new T cell reporter system, we have found that Nef more than doubles the number of cells expressing the transcription factors NF-kappaB and NFAT after TCR stimulation. This Nef-induced priming of TCR signaling pathways occurred independently of calcium signaling and involved a very proximal step before protein kinase C activation. Engagement of the TCR by MHC-bound Ag triggers the formation of the immunological synapse by recruiting detergent-resistant membrane microdomains, termed lipid rafts. Approximately 5-10% of the total cellular pool of Nef is localized within lipid rafts. Using confocal and real-time microscopy, we found that Nef in lipid rafts was recruited into the immunological synapse within minutes after Ab engagement of the TCR/CD3 and CD28 receptors. This recruitment was dependent on the N-terminal domain of Nef encompassing its myristoylation. Nef did not increase the number of cell surface lipid rafts or immunological synapses. Recently, studies have shown a specific interaction of Nef with an active subpopulation of p21-activated kinase-2 found only in the lipid rafts. Thus, the corecruitment of Nef and key cellular partners (e.g., activated p21-activated kinase-2) into the immunological synapse may underlie the increased frequency of cells expressing transcriptionally active forms of NF-kappaB and NFAT and the resultant changes in T cell activation.", "title": "Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement." }, { "docid": "22703082", "text": "Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IκB kinase–dependent nuclear factor-κB activation pathway. H. pylori–mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori–associated gastric carcinogenesis.", "title": "Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium" }, { "docid": "4702639", "text": "Tumour cells, with stem-like properties, are highly aggressive and often show drug resistance. Here, we reveal that integrin αvβ3 serves as a marker of breast, lung and pancreatic carcinomas with stem-like properties that are highly resistant to receptor tyrosine kinase inhibitors such as erlotinib. This was observed in vitro and in mice bearing patient-derived tumour xenografts or in clinical specimens from lung cancer patients who had progressed on erlotinib. Mechanistically, αvβ3, in the unliganded state, recruits KRAS and RalB to the tumour cell plasma membrane, leading to the activation of TBK1 and NF-κB. In fact, αvβ3 expression and the resulting KRAS–RalB–NF-κB pathway were both necessary and sufficient for tumour initiation, anchorage independence, self-renewal and erlotinib resistance. Pharmacological targeting of this pathway with bortezomib reversed both tumour stemness and erlotinib resistance. These findings not only identify αvβ3 as a marker/driver of carcinoma stemness but also reveal a therapeutic strategy to sensitize such tumours to RTK inhibition.", "title": "An integrin β3–KRAS–RalB complex drives tumour stemness and resistance to EGFR inhibition" }, { "docid": "23305884", "text": "Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that dramatically reorganizes host gene expression to immortalize primary B cells. In this study, we analyzed EBV-regulated host gene expression changes following primary B-cell infection, both during initial proliferation and through transformation into lymphoblastoid cell lines (LCLs). While most EBV-regulated mRNAs were changed during the transition from resting, uninfected B cells through initial B-cell proliferation, a substantial number of mRNAs changed uniquely from early proliferation through LCL outgrowth. We identified constitutively and dynamically EBV-regulated biological processes, protein classes, and targets of specific transcription factors. Early after infection, genes associated with proliferation, stress responses, and the p53 pathway were highly enriched. However, the transition from early to long-term outgrowth was characterized by genes involved in the inhibition of apoptosis, the actin cytoskeleton, and NF-κB activity. It was previously thought that the major viral protein responsible for NF-κB activation, latent membrane protein 1 (LMP1), is expressed within 2 days after infection. Our data indicate that while this is true, LCL-level LMP1 expression and NF-κB activity are not evident until 3 weeks after primary B-cell infection. Furthermore, heterologous NF-κB activation during the first week after infection increased the transformation efficiency, while early NF-κB inhibition had no effect on transformation. Rather, inhibition of NF-κB was not toxic to EBV-infected cells until LMP1 levels and NF-κB activity were high. These data collectively highlight the dynamic nature of EBV-regulated host gene expression and support the notion that early EBV-infected proliferating B cells have a fundamentally distinct growth and survival phenotype from that of LCLs.", "title": "Analysis of Epstein-Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-κB activation." }, { "docid": "29509926", "text": "Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels. In line with these findings, the innate immune responses required for clearance of P. aeruginosa bacterial infection in lung were compromised in mice with low HDL levels. Expression analysis, ChIP-PCR, and combinatorial pharmacological and genetic intervention studies unveiled that both native and reconstituted HDL enhance Toll-like-receptor-induced signaling by activating a PKC-NF-κB/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.", "title": "High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-κB/STAT1-IRF1 Signaling." }, { "docid": "4345315", "text": "Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle–Wells syndrome and neonatal-onset multiple-system inflammatory disease. Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the activation of intracellular host defence signalling pathways. Cryopyrin forms a multi-protein complex termed ‘the inflammasome’, which contains the apoptosis-associated speck-like protein (ASC) and caspase-1, and promotes caspase-1 activation and processing of pro-interleukin (IL)-1β (ref. 4). Here we show the effect of cryopyrin deficiency on inflammasome function and immune responses. Cryopyrin and ASC are essential for caspase-1 activation and IL-1β and IL-18 production in response to bacterial RNA and the imidazoquinoline compounds R837 and R848. In contrast, secretion of tumour-necrosis factor-α and IL-6, as well as activation of NF-κB and mitogen-activated protein kinases (MAPKs) were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like receptors and cryopyrin control the secretion of IL-1β and IL-18 through different intracellular pathways. These results reveal a critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1, and provide insights regarding the pathogenesis of autoinflammatory syndromes.", "title": "Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3" }, { "docid": "37138639", "text": "The IKK kinase complex is the core element of the NF-kappaB cascade. It is essentially made of two kinases (IKKalpha and IKKbeta) and a regulatory subunit, NEMO/IKKgamma. Additional components may exist, transiently or permanently, but their characterization is still unsure. In addition, it has been shown that two separate NF-kappaB pathways exist, depending on the activating signal and the cell type, the canonical (depending on IKKbeta and NEMO) and the noncanonical pathway (depending solely on IKKalpha). The main question, which is still only partially answered, is to understand how an NF-kappaB activating signal leads to the activation of the kinase subunits, allowing them to phosphorylate their targets and eventually induce nuclear translocation of the NF-kappaB dimers. I will review here the genetic, biochemical, and structural data accumulated during the last 10 yr regarding the function of the three IKK subunits.", "title": "The IKK complex, a central regulator of NF-kappaB activation." }, { "docid": "3118719", "text": "E-cadherin is best characterized as adherens junction protein, which through homotypic interactions contributes to the maintenance of the epithelial barrier function. In epithelial cells, the cytoplasmic tail of E-cadherin forms a dynamic complex with catenins and regulates several intracellular signal transduction pathways, including Wnt/β-catenin, PI3K/Akt, Rho GTPase, and NF-κB signaling. Recent progress uncovered a novel and critical role for this adhesion molecule in mononuclear phagocyte functions. E-cadherin regulates the maturation and migration of Langerhans cells, and its ligation prevents the induction of a tolerogenic state in bone marrow-derived dendritic cells (DCs). In this respect, the functionality of β-catenin could be instrumental in determining the balance between immunogenicity and tolerogenicity of DCs in vitro and in vivo. Fusion of alternatively activated macrophages and osteoclasts is also E-cadherin-dependent. In addition, the E-cadherin ligands CD103 and KLRG1 are expressed on DC-, T-, and NK-cell subsets and contribute to their interaction with E-cadherin-expressing DCs and macrophages. Here we discuss the regulation, function, and implications of E-cadherin expression in these central orchestrators of the immune system.", "title": "Regulation and function of the E-cadherin/catenin complex in cells of the monocyte-macrophage lineage and DCs." }, { "docid": "3761017", "text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.", "title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion" }, { "docid": "30224907", "text": "The c-Abl tyrosine kinase and its transforming variants have been implicated in tumorigenesis and in many important cellular processes. c-Abl is localized in the nucleus and the cytoplasm, where it plays distinct roles. The effects of c-Abl are mediated by multiple protein-protein and protein-DNA interactions and its tyrosine kinase domain. At the biochemical level, the mechanism of c-Abl kinase activation and the identification of its target proteins and cellular machineries have in part been solved. However, the phenotypic outcomes of these molecular events remained in large elusive. c-Abl has been shown to regulate the cell cycle and to induce under certain conditions cell growth arrest and apoptosis. In this respect the interaction of c-Abl with p53 and p73 has attracted particular attention. Recent findings have implicated c-Abl in an ionizing irradiation signaling pathway that elicits apoptosis. In this pathway p73 is an important immediate downstream effector. Here I review the current knowledge about these nuclear processes in which c-Abl is engaged and discuss some of their possible implications on cell physiology.", "title": "c-Abl: activation and nuclear targets" }, { "docid": "12785130", "text": "Src family kinases (SFKs) play critical roles in the regulation of many cellular functions by growth factors, G-protein-coupled receptors and ligand-gated ion channels. Recent data have shown that SFKs serve as a convergent point of multiple signaling pathways regulating N-methyl-d-aspartate (NMDA) receptors in the central nervous system. Multiple SFK molecules, such as Src and Fyn, closely associate with their substrate, NMDA receptors, via indirect and direct binding mechanisms. The NMDA receptor is associated with an SFK signaling complex consisting of SFKs; the SFK-activating phosphatase, protein tyrosine phosphatase α; and the SFK-inactivating kinase, C-terminal Src kinase. Early studies have demonstrated that intramolecular interactions with the SH2 or SH3 domain lock SFKs in a closed conformation. Disruption of the interdomain interactions can induce the activation of SFKs with multiple signaling pathways involved in regulation of this process. The enzyme activity of SFKs appears 'graded', exhibiting different levels coinciding with activation states. It has also been proposed that the SH2 and SH3 domains may stimulate catalytic activity of protein tyrosine kinases, such as Abl. Recently, it has been found that the enzyme activity of neuronal Src protein is associated with its stability, and that the SH2 and SH3 domain interactions may act not only to constrain the activation of neuronal Src, but also to regulate the enzyme activity of active neuronal Src. Collectively, these findings demonstrate novel mechanisms underlying the regulation of SFKs.", "title": "The regulation of N-methyl-D-aspartate receptors by Src kinase." }, { "docid": "28644298", "text": "Epstein-Barr virus (EBV) latency III infection converts B lymphocytes into lymphoblastoid cell lines (LCLs) by expressing EBV nuclear and membrane proteins, EBNAs, and latent membrane proteins (LMPs), which regulate transcription through Notch and tumor necrosis factor receptor pathways. The role of NF-kappa B in LMP1 and overall EBV latency III transcriptional effects was investigated by treating LCLs with BAY11-7082 (BAY11). BAY11 rapidly and irreversibly inhibited NF-kappa B, decreased mitochondrial membrane potential, induced apoptosis, and altered LCL gene expression. BAY11 effects were similar to those of an NF-kappa B inhibitor, Delta N-I kappa B alpha, in effecting decreased JNK1 expression and in microarray analyses. More than 80% of array elements that decreased with Delta N-I kappa B alpha expression decreased with BAY11 treatment. Newly identified NF-kappa B-induced, LMP1-induced, and EBV-induced genes included pleckstrin, Jun-B, c-FLIP, CIP4, and I kappa B epsilon. Of 776 significantly changed array elements, 134 were fourfold upregulated in EBV latency III, and 74 were fourfold upregulated with LMP1 expression alone, whereas only 28 were more than fourfold downregulated by EBV latency III. EBV latency III-regulated gene products mediate cell migration (EBI2, CCR7, RGS1, RANTES, MIP1 alpha, MIP1 beta, CXCR5, and RGS13), antigen presentation (major histocompatibility complex proteins and JAW1), mitogen-activated protein kinase pathway (DUSP5 and p62Dok), and interferon (IFN) signaling (IFN-gamma R alpha, IRF-4, and STAT1). Comparison of EBV latency III LCL gene expression to immunoglobulin M (IgM)-stimulated B cells, germinal-center B cells, and germinal-center-derived lymphomas clustered LCLs with IgM-stimulated B cells separately from germinal-center cells or germinal-center lymphoma cells. Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signaling pathways further distinguished EBV latency III-infected B cells from IgM-stimulated or germinal-center B cells.", "title": "Role of NF-kappa B in cell survival and transcription of latent membrane protein 1-expressing or Epstein-Barr virus latency III-infected cells." }, { "docid": "28006126", "text": "CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by B7 can generate TCR-independent signals leading to IkappaB kinase and NF-kappaB activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-kappaB-dependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of RelA and p52 NF-kappaB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-kappaB sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.", "title": "CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappaB subunits on IL-8 and Bcl-xL gene promoters." }, { "docid": "3504761", "text": "The MAP kinase kinase kinase TGFβ-activated kinase 1 (TAK1) is activated by TLRs, IL-1, TNF, and TGFβ and in turn activates IKK-NF-κB and JNK, which regulate cell survival, growth, tumorigenesis, and metabolism. TAK1 signaling also upregulates AMPK activity and autophagy. Here, we investigated TAK1-dependent regulation of autophagy, lipid metabolism, and tumorigenesis in the liver. Fasted mice with hepatocyte-specific deletion of Tak1 exhibited severe hepatosteatosis with increased mTORC1 activity and suppression of autophagy compared with their WT counterparts. TAK1-deficient hepatocytes exhibited suppressed AMPK activity and autophagy in response to starvation or metformin treatment; however, ectopic activation of AMPK restored autophagy in these cells. Peroxisome proliferator-activated receptor α (PPARα) target genes and β-oxidation, which regulate hepatic lipid degradation, were also suppressed in hepatocytes lacking TAK1. Due to suppression of autophagy and β-oxidation, a high-fat diet challenge aggravated steatohepatitis in mice with hepatocyte-specific deletion of Tak1. Notably, inhibition of mTORC1 restored autophagy and PPARα target gene expression in TAK1-deficient livers, indicating that TAK1 acts upstream of mTORC1. mTORC1 inhibition also suppressed spontaneous liver fibrosis and hepatocarcinogenesis in animals with hepatocyte-specific deletion of Tak1. These data indicate that TAK1 regulates hepatic lipid metabolism and tumorigenesis via the AMPK/mTORC1 axis, affecting both autophagy and PPARα activity.", "title": "TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis." }, { "docid": "54482327", "text": "Background/Aims: Osteoarthritis (OA) is a multifactorial disease that is associated with inflammation in joints. The purpose of the present study was to investigate the anti-inflammatory activity and mechanism of morin on human osteoarthritis chondrocytes stimulated by IL-1β. Methods: The levels of NO and PGE2 were measured by the Griess method and ELISA. The levels of MMP1, MMP3, and MMP13 were also measured by ELISA. Results: The results revealed that IL-1β significantly increased the production of NO, PGE2, MMP1, MMP3, and MMP13. Additionally, the increases were significantly attenuated by treatment with morin. Furthermore, IL-1β-induced NF-κB activation was suppressed by morin. In addition, the expression of Nrf2 and HO-1 were increased by morin and knockdown of Nrf2 could prevent the anti-inflammatory effects of morin. Conclusion: In conclusion, this study suggested that morin attenuated IL-1β-induced inflammation by activating the Nrf2 signaling pathway.", "title": "Morin Exhibits Anti-Inflammatory Effects on IL-1β-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway" }, { "docid": "27403802", "text": "The NF-kappaB signaling pathway plays a crucial role in the immune, inflammatory, and apoptotic responses. Recently, we identified the NF-kappaB Essential Modulator (NEMO) as an essential component of this pathway. NEMO is a structural and regulatory subunit of the high molecular kinase complex (IKK) responsible for the phosphorylation of NF-kappaB inhibitors. Data base searching led to the isolation of a cDNA encoding a protein we called NRP (NEMO-related protein), which shows a strong homology to NEMO. Here we show that NRP is present in a novel high molecular weight complex, that contains none of the known members of the IKK complex. Consistently, we could not observe any effect of NRP on NF-kappaB signaling. Nonetheless, we could demonstrate that treatment with phorbol esters induces NRP phosphorylation and decreases its half-life. This phosphorylation event could only be inhibited by K-252a and stauroporin. We also show that de novo expression of NRP can be induced by interferon and tumor necrosis factor alpha and that these two stimuli have a synergistic effect on NRP expression. In addition, we observed that endogenous NRP is associated with the Golgi apparatus. Analogous to NEMO, we find that NRP is associated in a complex with two kinases, suggesting that NRP could play a similar role in another signaling pathway.", "title": "Phorbol esters and cytokines regulate the expression of the NEMO-related protein, a molecule involved in a NF-kappa B-independent pathway." }, { "docid": "14615911", "text": "We developed a novel mouse model of malignant pleural effusion (MPE) by injecting Lewis lung cancer (LLC) cells directly into the pleural space of syngeneic C57B/6 mice. The pleural effusions in this model share common cellular and biochemical features with human MPEs. Implantation and growth of pleural tumors triggers a host inflammatory response characterized by a mixed inflammatory cell influx into the pleural fluid. LLC cells exhibited high basal nuclear factor (NF)-κB activity in vitro and in vivo, which we used to drive expression of a NF-κB–dependent green fluorescent protein-firefly luciferase fusion reporter construct. NF-κB–dependent reporter expression allowed intravital tracing of pleural tumors. Inhibition of NF-κB in LLC cells did not affect cell viability in culture; however, injection of LLC cells expressing a dominant NF-κB inhibitor resulted in decreased tumor burden, decreased pleural effusion volume, and decreased pleural effusion TNF-α levels. These studies indicate that tumor NF-κB a...", "title": "Nuclear Factor-�B Affects Tumor Progression in a Mouse Model of Malignant Pleural Effusion" } ]
391	Ethanol stress increases the expression of SRL in bacteria.	[ { "docid": "1148122", "text": "Understanding the genetic basis of adaptation is a central problem in biology. However, revealing the underlying molecular mechanisms has been challenging as changes in fitness may result from perturbations to many pathways, any of which may contribute relatively little. We have developed a combined experimental/computational framework to address this problem and used it to understand the genetic basis of ethanol tolerance in Escherichia coli. We used fitness profiling to measure the consequences of single-locus perturbations in the context of ethanol exposure. A module-level computational analysis was then used to reveal the organization of the contributing loci into cellular processes and regulatory pathways (e.g. osmoregulation and cell-wall biogenesis) whose modifications significantly affect ethanol tolerance. Strikingly, we discovered that a dominant component of adaptation involves metabolic rewiring that boosts intracellular ethanol degradation and assimilation. Through phenotypic and metabolomic analysis of laboratory-evolved ethanol-tolerant strains, we investigated naturally accessible pathways of ethanol tolerance. Remarkably, these laboratory-evolved strains, by and large, follow the same adaptive paths as inferred from our coarse-grained search of the fitness landscape.", "title": "Regulatory and metabolic rewiring during laboratory evolution of ethanol tolerance in E. coli" } ]	[ { "docid": "21602220", "text": "The physiology of ethanologenic Escherichia coli grown anaerobically in alkali-pretreated plant hydrolysates is complex and not well studied. To gain insight into how E. coli responds to such hydrolysates, we studied an E. coli K-12 ethanologen fermenting a hydrolysate prepared from corn stover pretreated by ammonia fiber expansion. Despite the high sugar content (∼6% glucose, 3% xylose) and relatively low toxicity of this hydrolysate, E. coli ceased growth long before glucose was depleted. Nevertheless, the cells remained metabolically active and continued conversion of glucose to ethanol until all glucose was consumed. Gene expression profiling revealed complex and changing patterns of metabolic physiology and cellular stress responses during an exponential growth phase, a transition phase, and the glycolytically active stationary phase. During the exponential and transition phases, high cell maintenance and stress response costs were mitigated, in part, by free amino acids available in the hydrolysate. However, after the majority of amino acids were depleted, the cells entered stationary phase, and ATP derived from glucose fermentation was consumed entirely by the demands of cell maintenance in the hydrolysate. Comparative gene expression profiling and metabolic modeling of the ethanologen suggested that the high energetic cost of mitigating osmotic, lignotoxin, and ethanol stress collectively limits growth, sugar utilization rates, and ethanol yields in alkali-pretreated lignocellulosic hydrolysates.", "title": "Complex physiology and compound stress responses during fermentation of alkali-pretreated corn stover hydrolysate by an Escherichia coli ethanologen." }, { "docid": "24019260", "text": "Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.", "title": "Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking." }, { "docid": "471735", "text": "Escherichia coli responds to the redox stress imposed by superoxide-generating agents such as paraquat by activating the synthesis of as many as 80 polypeptides. Expression of a key group of these inducible proteins is controlled at the transcriptional level by the soxRS locus (the soxRS regulon). A two-stage control system was hypothesized for soxRS, in which an intracellular redox signal would trigger the SoxR protein as a transcriptional activator of the soxS gene and the resulting increased levels of SoxS protein would activate transcription of the various soxRS regulon genes (B. Demple and C.F. Amábile Cuevas, Cell 67:837-839, 1990). We have constructed operon fusions of the E. coli lac genes to the soxS promoter to monitor soxS transcription. Expression from the soxS promoter is strongly inducible by paraquat in a manner strictly dependent on a functional soxR gene. Several other superoxide-generating agents also trigger soxR(+)-dependent soxS expression, and the inductions by paraquat and phenazine methosulfate were dependent on the presence of oxygen. Numerous other oxidative stress agents (H2O2, gamma rays, heat shock, etc.) failed to induce soxS, while aerobic growth of superoxide dismutase-deficient bacteria triggered soxR-dependent soxS expression. These results indicate a specific redox signal for soxS induction. A direct role for SoxR protein in the activation of the soxS gene is indicated by band-shift and DNase I footprinting experiments that demonstrate specific binding of the SoxR protein in cell extracts to the soxS promoter. The mode of SoxR binding to DNA appears to be similar to that of its homolog MerR in that the SoxR footprint spans the -10 to -35 region of the soxS promoter.", "title": "Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene." }, { "docid": "28025754", "text": "TO enable staining of insoluble calcium salts with glyoxal bis(2-hydroxyanil) (GBHA), the original solution containing 2 ml of 0.4% GBHA in absolute ethanol, and 0.3 ml of aqueous 5% NaOH, and limited to staining only soluble calcium salts, was modified as follows: 1, 2 ml of 0.4% GBHA in absolute ethanol in 0.6 ml of 10% aqueous NaOH; 11, 0.1 gm GBHA in 2 ml of 3.4% NaOH in 75% ethanol. To prevent diffusion and loss of calcium, the tissues were processed by the freeze-substitution or freeze-dry method and sections stained without removing the paraffin. Modification I is effective only when 1 or 2 drops placed on the section are evaporated gradually to dryness, concentrating the GBHA and NaOH on the insoluble calcium salts. Modification II is effective when dried or poured on the the section and allowed to stain for 5 min. The stained slides are immersed for 15 min in 90% ethanol saturated with KCN and Na2CO3 for specificity to calcium; rinsed and counterstained in 95% ethanol containing 0.1% each of fast...", "title": "THE GLYOXAL BIS(2-HYDROXYANIL) METHOD MODIFIED FOR LOCALIZING INSOLUBLE CALCIUM SALTS." }, { "docid": "22908536", "text": "Nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following \"sterilizing\" chemotherapy. However, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. Here we measure the single-cell dynamics of Mycobacterium tuberculosis replication and ribosomal activity using quantitative time-lapse microscopy and a reporter of ribosomal RNA gene expression. Single-cell dynamics exhibit heterogeneity under standard growth conditions, which is amplified by stressful conditions such as nutrient limitation, stationary phase, intracellular replication, and growth in mouse lungs. Additionally, the lungs of chronically infected mice harbor a subpopulation of nongrowing but metabolically active bacteria, which are absent in mice lacking interferon-γ, a cytokine essential for antituberculosis immunity. These cryptic bacterial forms are prominent in mice treated with the antituberculosis drug isoniazid, suggesting a role in postchemotherapeutic relapses. Thus, amplification of bacterial phenotypic heterogeneity in response to host immunity and drug pressure may contribute to tuberculosis persistence.", "title": "Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms." }, { "docid": "6251620", "text": "Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80-90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10-20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10-20% of patients with WG or MPA (and 40-50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear. ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.", "title": "Antineutrophil cytoplasmic antibodies (ANCA)." }, { "docid": "4641348", "text": "BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.", "title": "Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease" }, { "docid": "21373821", "text": "A series of 33 patients with combined (injurious) sleepwalking, sleep terrors, and rapid eye movement (REM) sleep behavior disorder (viz. \"parasomnia overlap disorder\") was gathered over an 8-year period. Patients underwent clinical and polysomnographic evaluations. Mean age was 34 +/- 14 (SD) years; mean age of parasomnia onset was 15 +/- 16 years (range 1-66); 70% (n = 23) were males. An idiopathic subgroup (n = 22) had a significantly earlier mean age of parasomnia onset (9 +/- 7 years) than a symptomatic subgroup (n = 11) (27 +/- 23 years, p = 0.002), whose parasomnia began with either of the following: neurologic disorders, n = 6 [congenital Mobius syndrome, narcolepsy, multiple sclerosis, brain tumor (and treatment), brain trauma, indeterminate disorder (exaggerated startle response/atypical cataplexy)]; nocturnal paroxysmal atrial fibrillation, n = 1; posttraumatic stress disorder/major depression, n = 1; chronic ethanol/amphetamine abuse and withdrawal, n = 1; or mixed disorders (schizophrenia, brain trauma, substance abuse), n = 2. The rate of DSM-III-R (Diagnostic and Statistical Manual, 3rd edition, revised) Axis 1 psychiatric disorders was not elevated; group scores on various psychometric tests were not elevated. Forty-five percent (n = 15) had previously received psychologic or psychiatric therapy for their parasomnia, without benefit. Treatment outcome was available for n = 20 patients; 90% (n = 18) had substantial parasomnia control with bedtime clonazepam (n = 13), alprazolam and/or carbamazepine (n = 4), or self-hypnosis (n = 1). Thus, \"parasomnia overlap disorder\" is a treatable condition that emerges in various clinical settings and can be understood within the context of current knowledge on parasomnias and motor control/dyscontrol during sleep.", "title": "A parasomnia overlap disorder involving sleepwalking, sleep terrors, and REM sleep behavior disorder in 33 polysomnographically confirmed cases." }, { "docid": "27396415", "text": "OBJECTIVE To establish high cell density cultivation process of recombinant Helicobacter pylori multi-epitope vaccine engineering bacteria BIB. METHODS Based on the results of shake flask fermentation, the process was magnified into volume of a 50 L fermenter to optimize and verify the factors affecting the yield of the target protein, such as the fermentation medium, working seed inoculation amount, inducer concentration, induction starting time, induction duration, inducer adding mode and feeding strategy. RESULTS After activated in modified TB medium at 37°C for 8 h, the BIB working seed was inoculated at 5% (v/v) and was induced for expression for another 11 h by the final concentration of 5 mmol/L lactose. In growth phase, glucose at rate of 80 ml/h was used as carbon source, and in induction phase, glycerol at rate of 40 ml/h was used as carbon source; ammonia water was added dropwise to control pH at about 7.0, and revolution speed is adjusted to control the dissolved oxygen at above 30%; ultimately the output of bacterial body was 70 g/L and protein expression amount was about 32%. CONCLUSION After high cell density cultivation of the recombinant engineering bacteria, expression and yield of the target protein rBIB significantly increased.", "title": "A study of high cell density cultivation process of recombinant Helicobacter pylori multi-epitope vaccine engineering bacteria." }, { "docid": "25293721", "text": "Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F2-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.", "title": "Antioxidant Defenses in the Rat Placenta in Late Gestation: Increased Labyrinthine Expression of Superoxide Dismutases, Glutathione Peroxidase 3, and Uncoupling Protein 21" }, { "docid": "25510546", "text": "Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.", "title": "Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes" }, { "docid": "44562221", "text": "Endogenous glucocorticoids (GC) play an important role in the termination of the inflammatory response following infection and tissue injury. However, recent findings indicate that stress can impair the anti-inflammatory capacities of these hormones. Lipopolysaccharide (LPS)-stimulated splenocytes of mice that were repeatedly subjected to social disruption (SDR) stress were less sensitive to the immunosuppressive effects of corticosterone (CORT) as demonstrated by an increased production of pro-inflammatory cytokines and enhanced cell survival. Myeloid cells expressing the marker CD11b were shown to play a key role in this process. Here we investigated the role of the bone marrow as a potential source of the GC-insensitive cells. The study revealed that LPS-stimulated bone marrow cells, in the absence of experimental stress, were virtually GC-resistant and retained high levels of cell viability after treatment with CORT. Recurrent exposure to the acute stressor over a period of 2, 4 or 6 days led to an increase in the GC sensitivity of the bone marrow cells. This increase in GC sensitivity was associated with enhanced mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), an increase in the number of myeloid progenitors, and a decrease in the proportion of mature CD11b+ cells. The changes in the cellular composition of the bone marrow were accompanied by an increase in splenic CD11b+ cell numbers. Simultaneous assessment of the GC sensitivity in bone marrow and spleen revealed a significant negative correlation between both tissues suggesting that social stress causes the redistribution of GC-insensitive myeloid cells from the bone marrow to the spleen.", "title": "Tissue-specific alterations in the glucocorticoid sensitivity of immune cells following repeated social defeat in mice" }, { "docid": "9588931", "text": "Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production. Disruption of mitochondrial structural integrity was also observed in a rat model of adenine-induced aortic calcification. Increased production of reactive oxygen species, enhanced expression and phosphorylation of Drp1, and excessive mitochondrial fragmentation were also observed in Pi-treated VSMCs. These effects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol and subsequent activation of caspase-3. Quercetin was shown to block Pi-induced apoptosis and calcification of VSMCs by inhibiting oxidative stress and decreasing mitochondrial fission by inhibiting the expression and phosphorylation of Drp1. Quercetin also significantly ameliorated adenine-induced aortic calcification in rats. In summary, our findings suggest that quercetin attenuates calcification by reducing apoptosis of VSMCs by blocking oxidative stress and inhibiting mitochondrial fission.", "title": "Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission." }, { "docid": "12658073", "text": "The gut microbiota has been proposed as an environmental factor that affects the development of metabolic and inflammatory diseases in mammals. Recent reports indicate that gut bacteria-derived lipopolysaccharide (LPS) can initiate obesity and insulin resistance in mice; however, the molecular interactions responsible for microbial regulation of host metabolism and mediators of inflammation have not been studied in detail. Hepatic serum amyloid A (SAA) proteins are markers and proposed mediators of inflammation that exhibit increased levels in serum of insulin-resistant mice. Adipose tissue-derived SAA3 displays monocyte chemotactic activity and may play a role in metabolic inflammation associated with obesity and insulin resistance. To investigate a potential mechanistic link between the intestinal microbiota and induction of proinflammatory host factors, we performed molecular analyses of germ-free, conventionally raised and genetically modified Myd88-/- mouse models. SAA3 expression was determined to be significantly augmented in adipose (9.9+/-1.9-fold; P<0.001) and colonic tissue (7.0+/-2.3-fold; P<0.05) by the presence of intestinal microbes. In the colon, we provided evidence that SAA3 is partially regulated through the Toll-like receptor (TLR)/MyD88/NF-kappaB signaling axis. We identified epithelial cells and macrophages as cellular sources of SAA3 in the colon and found that colonic epithelial expression of SAA3 may be part of an NF-kappaB-dependent response to LPS from gut bacteria. In vitro experiments showed that LPS treatments of both epithelial cells and macrophages induced SAA3 expression (27.1+/-2.5-fold vs. 1.6+/-0.1-fold, respectively). Our data suggest that LPS, and potentially other products of the indigenous gut microbiota, might elevate cytokine expression in tissues and thus exacerbate chronic low-grade inflammation observed in obesity.", "title": "Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota" }, { "docid": "12903921", "text": "It has been proved that oxidative stress increases when leukemia is accompanied by depression. This fact may indicate the role of oxidative stress in the development of depression in cancer patients. The aim of this study was to determine whether the acute myeloid leukemia of Brown Norway rats, which is accompanied by oxidative stress, evoked behavioral and receptor changes resembling alterations characteristic of rat models of depression. The rats were divided into two groups: leukemic rats and healthy control. Leukemia was induced through intraperitoneal injection of 10(7) promyelocytic leukemia cells to the Brown Norway rats. Depression-like behavior was evaluated in the forced swim test at 30 or 34 days after leukemic cells injection. The rats were killed after the evaluation and the spleen, brain cortex and hippocampus were excised. The red-ox state was assessed in homogenates of tissues by measuring total glutathione (GSH) content, the ferric ion reducing ability of plasma (FRAP) level, expression of heme oxygenase-1 (HO-1), biliverdin reductase (BvR) and ferritin mRNA, superoxide dismutase (SOD) activity, as well as malondialdehyde (MDA) concentration. Radioligand binding assay was used to assess of the effect of leukemia on cortical receptors. Leukemic cells were identified using RM-124 antibody by FACS Calibur flow cytometry. Leukemia influenced locomotory activity as well as forced swim test behavior in a 34-day series of experiments. Signs of oxidative stress in leukemic rats were observed in each examined stage of leukemia development. The FRAP values and glutathione contents, were significantly lowered whereas HO-1 mRNA expression, and malonodialdehyde concentrations were significantly increased in the spleen and brain structures of leukemic rats in comparison with the healthy controls. A significant increase in the potency of glycine to displace [(3)H]L-689,560 from the strychnine-insensitive glycine site of the N-methyl-D-aspartic (NMDA) receptors receptor complex in cortical homogenates of the leukemic rats in 30- and 34-day experimental series was observed in comparison with the control. Upregulation of 5-HT(2A) receptors was observed in rat cortex after 30 days of leukemia development but not in 34-days series compared with the control. It is concluded that disturbances in antioxidant system in brain cortex were accompanied by an activation of glycine sites of the NMDA receptor complex, regardless of stage of leukemia development, which are characteristic of model of depression. Findings of our study demonstrate the link between glutamatergic activity, oxidative stress and leukemia.", "title": "Evaluation of oxidative status and depression-like responses in Brown Norway rats with acute myeloid leukemia" }, { "docid": "28517384", "text": "Myeloid differentiation factor-2 (MD-2) is a lipopolysaccharide (LPS)-binding protein usually coexpressed with and binding to Toll-like receptor 4 (TLR4), conferring LPS responsiveness of immune cells. MD-2 is also found as a soluble protein. Soluble MD-2 (sMD-2) levels are markedly elevated in plasma from patients with severe infections, and in other fluids from inflamed tissues. We show that sMD-2 is a type II acute-phase protein. Soluble MD-2 mRNA and protein levels are up-regulated in mouse liver after the induction of an acute-phase response. It is secreted by human hepatocytic cells and up-regulated by interleukin-6. Soluble MD-2 binds to Gram-negative but not Gram-positive bacteria, and sMD-2 secreted by hepatocytic cells is an essential cofactor for the activation of TLR4-expressing cells by Gram-negative bacteria. Soluble MD-2 opsonization of Gram-negative bacteria accelerates and enhances phagocytosis, principally by polymorphonuclear neutrophils. In summary, our results demonstrate that sMD-2 is a newly recognized type II acute-phase reactant, an opsonin for Gram-negative bacteria, and a cofactor essential for the activation of TLR4-expressing cells. This suggests that sMD-2 plays a key role in the host innate immune response to Gram-negative infections.", "title": "Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria." }, { "docid": "7506409", "text": "Human mesenchymal stem cells (hMSCs) have been widely studied as a source of primary adult stem cells for cell therapy because of their multidifferentiation potential; however, the growth arrest (also known as \"premature senescence\") often found in hMSCs cultured in vitro has been a major obstacle to the in-depth characterization of these cells. In addition, the inability to maintain constant cell growth hampers the development of additional genetic modifications aimed at achieving desired levels of differentiation to specific tissues; however, the molecular mechanisms that govern this phenomenon remain unclear, with the exception of a few studies demonstrating that induction of p16INK4a is responsible for this senescence-like event. Here, we observed that the premature growth arrest in hMSCs occurs in parallel with the induction of p16INK4a, following abrogation of inhibitory phosphorylation of retinoblastoma protein. These stress responses were concurrent with increased formation of reactive oxygen species (ROSs) from mitochondria and increased p38 mitogen-activated protein kinase (MAPK) activity. The introduction of Wip1 (wild-type p53 inducible phosphatase-1), a well-studied stress modulator, significantly lowered p16INK4a expression and led to p38 MAPK inactivation, although it failed to affect the levels of ROSs. Moreover, the suppression of stress responses by Wip1 apparently extended the life span of hMSCs, compared with control conditions, while maintaining their multilineage differentiation potential. Based on these results, we suggest that senescent growth arrest in hMSCs may result from activation of stress signaling pathways and consequent onset of stress responses, due in part to ROS production during prolonged in vitro culture.", "title": "Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1-mediated downregulation of intrinsic stress signaling pathways." }, { "docid": "24349992", "text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.", "title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells." }, { "docid": "12909503", "text": "DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes replication stress, characterized by accumulation of single-stranded DNA bound by replication protein A (RPA), which triggers activation of ataxia telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated (ATM) and ATR] has well characterized roles in DNA double-strand break repair, but poorly understood roles in replication stress-induced RPA phosphorylation. We show that DNA-PKcs mutant cells fail to arrest replication following stress, and mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA-PKcs show sustained H2AX phosphorylation in response to replication stress that persists in cells entering mitosis, indicating inappropriate mitotic entry with unrepaired damage.", "title": "Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress" }, { "docid": "6259170", "text": "Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) was originally identified as a positive regulator of drug detoxifying enzyme gene expression during exposure to environmental electrophiles. Currently, Nrf2 is known to regulate the expression of hundreds of cytoprotective genes to counteract endogenously or exogenously generated oxidative stress. Furthermore, when activated in human tumors by somatic mutations, Nrf2 confers growth advantages and chemoresistance by regulating genes involved in various processes such as the pentose phosphate pathway and nucleotide synthesis in addition to antioxidant proteins. Interestingly, increasing evidence shows that Nrf2 is associated with mitochondrial biogenesis during environmental stresses in certain tissues such as the heart. Furthermore, SKN-1, a functional homolog of Nrf2 in C. elegans, is activated by mitochondrial reactive oxygen species and extends life span by promoting mitochondrial homeostasis (i.e., mitohormesis). Similarly, Nrf2 activation was recently observed in the heart of surfeit locus protein 1 (Surf1) -/- mice in which cellular respiration was decreased due to cytochrome c oxidase defects. In this review, we critically examine the relationship between Nrf2 and mitochondria and argue that the Nrf2 stress pathway intimately communicates with mitochondria to maintain cellular homeostasis during oxidative stress.", "title": "Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria" }, { "docid": "3943235", "text": "During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.", "title": "Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress" }, { "docid": "22153455", "text": "Although gram-positive infections account for the majority of cases of sepsis, the molecular mechanisms underlying their effects remains poorly understood. We investigated how cell wall components of gram-positive bacteria contribute to the development of sepsis. Experimental observations derived from cultured primary macrophages and the cell line indicate that gram-positive bacterial endotoxins induce hypoxia-inducible factor 1α (HIF-1α) mRNA and protein expression. Inoculation of live or heat-inactivated gram-positive bacteria with macrophages induced HIF-1 transcriptional activity in macrophages. Concordant with these results, myeloid deficiency of HIF-1α attenuated gram-positive bacterial endotoxin-induced cellular motility and proinflammatory gene expression in macrophages. Conversely, gram-positive bacteria and their endotoxins reduced expression of the myeloid anti-inflammatory transcription factor Krüppel-like transcription factor 2 (KLF2). Sustained expression of KLF2 reduced and deficiency of KLF2 enhanced gram-positive endotoxins induced HIF-1α mRNA and protein expression in macrophages. More importantly, KLF2 attenuated gram-positive endotoxins induced cellular motility and proinflammatory gene expression in myeloid cells. Consistent with these results, mice deficient in myeloid HIF-1α were protected from gram-positive endotoxin-induced sepsis mortality and clinical symptomatology. By contrast, myeloid KLF2-deficient mice were susceptible to gram-positive sepsis induced mortality and clinical symptoms. Collectively, these observations identify HIF-1α and KLF2 as critical regulators of gram-positive endotoxin-mediated sepsis.", "title": "A myeloid hypoxia-inducible factor 1α-Krüppel-like factor 2 pathway regulates gram-positive endotoxin-mediated sepsis." }, { "docid": "1887056", "text": "OBJECTIVE The authors sought to determine innate immune system activation following psychosocial stress in patients with major depression and increased early life stress. METHOD Plasma interleukin (IL)-6, lymphocyte subsets, and DNA binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were compared in medically healthy male subjects with current major depression and increased early life stress (N=14) versus nondepressed male comparison subjects (N=14) before and after completion of the Trier Social Stress Test. RESULTS Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were greater in major depression patients with increased early life stress and independently correlated with depression severity, but not early life stress. Natural killer (NK) cell percentages also increased following stress. However, there were no differences between groups and no correlation between NK cell percentage and stress-induced NF-kappaB DNA-binding or IL-6. CONCLUSIONS Male major depression patients with increased early life stress exhibit enhanced inflammatory responsiveness to psychosocial stress, providing preliminary indication of a link between major depression, early life stress and adverse health outcomes in diseases associated with inflammation.", "title": "Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress." }, { "docid": "16546131", "text": "Hydroxyurea is a potent teratogen; free radical scavengers or antioxidants reduce its teratogenicity. Activator Protein-1 (AP-1) and NF-kappaB are redox-sensitive transcription factors with important roles in normal development and the stress response. This study was designed to determine if exposure to teratogenic doses of hydroxyurea induces oxidative stress and alters gene expression by activating these transcription factors. Pregnant mice were treated with saline or hydroxyurea (400, 500, or 600 mg/kg) on gestation day 9 (GD 9) and killed either on GD 9, 0.5, 3, or 6 h after treatment, to assess oxidative stress and transcription factor activities, or on GD 18, to assess fetal development. Exposure to 400 mg/kg hydroxyurea did not affect the progeny, whereas exposure to 500 or 600 mg/kg resulted in dose-dependent increases in fetal resorptions and malformations, including curly tails, abnormal limbs (oligodactyly, hemimelia, and amelia), and short ribs. Hydroxyurea did not induce oxidative stress, as assessed by the ratio of oxidized to reduced glutathione, nor did it alter NF-kappaB DNA binding activity in the GD 9 conceptus. In contrast, exposure to hydroxyurea at any dose increased AP-1 DNA binding activity in embryos and yolk sacs 0.5 or 3 h after treatment. Hydroxyurea-induced c-Fos heterodimer activity in the embryo peaked 3-4-fold above control at 3 h and remained elevated by 6 h; in contrast, the activity of c-Jun dimers was not altered by drug exposure. A dramatic and region-specific increase in c-Fos immunoreactivity was found in hydroxyurea-treated embryos. The induction of AP-1 DNA binding activity by hydroxyurea represents an early, sensitive marker of the embryonic response to insult.", "title": "Activator protein-1 (AP-1) DNA binding activity is induced by hydroxyurea in organogenesis stage mouse embryos" }, { "docid": "35085326", "text": "A previously unknown protein, designated SvpA (surface virulence-associated protein) and implicated in the virulence of the intracellular pathogen Listeria monocytogenes, was identified. This 64 kDa protein, encoded by svpA, is both secreted in culture supernatants and surface-exposed, as shown by immunogold labelling of whole bacteria with an anti-SvpA antibody. Analysis of the peptide sequence revealed that SvpA contains a leader peptide, a predicted C-terminal transmembrane region and a positively charged tail resembling that of the surface protein ActA, suggesting that SvpA might partially reassociate with the bacterial surface by its C-terminal membrane anchor. An allelic mutant was constructed by disrupting svpA in the wild-type strain LO28. The virulence of this mutant was strongly attenuated in the mouse, with a 2 log decrease in the LD50 and restricted bacterial growth in organs as compared to the wild-type strain. This reduced virulence was not related either to a loss of adherence or to a lower expression of known virulence factors, which remained unaffected in the svpA mutant. It was caused by a restriction of intracellular growth of mutant bacteria. By following the intracellular behaviour of bacteria within bone-marrow-derived macrophages by confocal and electron microscopy studies, it was found that most svpA mutant bacteria remained confined within phagosomes, in contrast to wild-type bacteria which rapidly escaped to the cytoplasm. The regulation of svpA was independent of PrfA, the transcriptional activator of virulence genes in L. monocytogenes. In fact, SvpA was down-regulated by MecA, ClpC and ClpP, which are highly homologous to proteins of Bacillus subtilis forming a regulatory complex controlling the competence state of this saprophyte. The results indicate that: (i) SvpA is a novel factor involved in the virulence of L. monocytogenes, promoting bacterial escape from phagosomes of macrophages; (ii) SvpA is, at least partially, associated with the surface of bacteria; and (iii) SvpA is PrfA-independent and controlled by a MecA-dependent regulatory network.", "title": "SvpA, a novel surface virulence-associated protein required for intracellular survival of Listeria monocytogenes." }, { "docid": "9194077", "text": "Pathogenesis of Alzheimer’s disease (AD), which is characterised by accumulation of extracellular deposits of β-amyloid peptide (Aβ) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Aβ is constantly produced in the brain from amyloid precursor protein (APP) through its cleavage by β- and γ-secretases and certain Aβ species are toxic for neurones. The brain has an endogenous mechanism of Aβ removal via proteolytic degradation and the zinc metalloproteinase neprilysin (NEP) is a critical regulator of Aβ concentration. Down-regulation of NEP could predispose to AD. By comparing the effects of hypoxia and oxidative stress on expression and activity of the Aβ-degrading enzyme NEP in human neuroblastoma NB7 cells and rat primary cortical neurones we have demonstrated that hypoxia reduced NEP expression at the protein and mRNA levels as well as its activity. On contrary in astrocytes hypoxia increased NEP mRNA expression.", "title": "Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes" }, { "docid": "34386619", "text": "The Bacillus subtilis clpC operon is regulated by two stress induction pathways relying on either sigmaB or a class III stress induction mechanism acting at a sigmaA-like promoter. When the clpC operon was placed under the control of the isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible Pspac promoter, dramatic repression of the natural clpC promoters fused to a lacZ reporter gene was noticed after IPTG induction. This result strongly indicated negative regulation of the clpC operon by one of its gene products. Indeed, the negative regulator could be identified which is encoded by the first gene of the clpC operon, ctsR, containing a predicted helix-turn-helix DNA-binding motif. Deletion of ctsR abolished the negative regulation and resulted in high expression of both the clpC operon and the clpP gene under nonstressed conditions. Nevertheless, a further increase in clpC and clpP mRNA levels was observed after heat shock, even in the absence of sigmaB, suggesting a second induction mechanism at the vegetative promoter. Two-dimensional gel analysis and mRNA studies showed that the expression of other class III stress genes was at least partially influenced by the ctsR deletion. Studies with different clpC promoter fragments either fused to the reporter gene bgaB or used in gel mobility shift experiments with the purified CtsR protein revealed a possible target region where the repressor seemed to bind in vivo and in vitro. Our data demonstrate that the CtsR protein acts as a global repressor of the clpC operon, as well as other class III heat shock genes, by preventing unstressed transcription from either the sigmaB- or sigmaA-dependent promoter and might be inactivated or dissociate under inducing stress conditions.", "title": "The first gene of the Bacillus subtilis clpC operon, ctsR, encodes a negative regulator of its own operon and other class III heat shock genes." }, { "docid": "22312627", "text": "Previous results have demonstrated that the silencing of adjacent genes encoding NADPH-dependent furfural oxidoreductases (yqhD dkgA) is responsible for increased furfural tolerance in an E. coli strain EMFR9 [Miller et al., Appl Environ Microbiol 75:4315–4323, 2009]. This gene silencing is now reported to result from the spontaneous insertion of an IS10 into the coding region of yqhC, an upstream gene. YqhC shares homology with transcriptional regulators belonging to the AraC/XylS family and was shown to act as a positive regulator of the adjacent operon encoding YqhD and DkgA. Regulation was demonstrated by constructing a chromosomal deletion of yqhC, a firefly luciferase reporter plasmid for yqhC, and by a direct comparison of furfural resistance and NADPH-dependent furfural reductase activity. Closely related bacteria contain yqhC, yqhD, and dkgA orthologs in the same arrangement as in E. coli LY180. Orthologs of yqhC are also present in more distantly related Gram-negative bacteria. Disruption of yqhC offers a useful approach to increase furfural tolerance in bacteria.", "title": "YqhC regulates transcription of the adjacent Escherichia coli genes yqhD and dkgA that are involved in furfural tolerance" }, { "docid": "25488034", "text": "Increases in the intracellular levels of reactive oxygen species (ROS), frequently referred to as oxidative stress, represents a potentially toxic insult which if not counteracted will lead to membrane dysfunction, DNA damage and inactivation of proteins. Chronic oxidative stress has numerous pathological consequences including cancer, arthritis and neurodegenerative disease. Glutathione-associated metabolism is a major mechanism for cellular protection against agents which generate oxidative stress. It is becoming increasingly apparent that the glutathione tripeptide is central to a complex multifaceted detoxification system, where there is substantial inter-dependence between separate component members. Glutathione participates in detoxification at several different levels, and may scavenge free radicals, reduce peroxides or be conjugated with electrophilic compounds. Thus, glutathione provides the cell with multiple defences not only against ROS but also against their toxic products. This article discusses how glutathione biosynthesis, glutathione peroxidases, glutathione S-transferases and glutathione S-conjugate efflux pumps function in an integrated fashion to allow cellular adaption to oxidative stress. Co-ordination of this response is achieved, at least in part, through the antioxidant responsive element (ARE) which is found in the promoters of many of the genes that are inducible by oxidative and chemical stress. Transcriptional activation through this enhancer appears to be mediated by basic leucine zipper transcription factors such as Nrf and small Maf proteins. The nature of the intracellular sensor(s) for ROS and thiol-active chemicals which induce genes through the ARE is described. Gene activation through the ARE appears to account for the enhanced antioxidant and detoxification capacity of normal cells effected by many cancer chemopreventive agents. In certain instances it may also account for acquired resistance of tumours to cancer chemotherapeutic drugs. It is therefore clear that determining the mechanisms involved in regulation of ARE-driven gene expression has enormous medical implications.", "title": "Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress." }, { "docid": "32454714", "text": "Mucosal tolerance has been considered a potentially important pathway for the treatment of autoimmune disease, including human multiple sclerosis and experimental conditions such as experimental autoimmune encephalomyelitis (EAE). There is limited information on the capacity of commensal gut bacteria to induce and maintain peripheral immune tolerance. Inbred SJL and C57BL/6 mice were treated orally with a broad spectrum of antibiotics to reduce gut microflora. Reduction of gut commensal bacteria impaired the development of EAE. Intraperitoneal antibiotic-treated mice showed no significant decline in the gut microflora and developed EAE similar to untreated mice, suggesting that reduction in disease activity was related to alterations in the gut bacterial population. Protection was associated with a reduction of proinflammatory cytokines and increases in IL-10 and IL-13. Adoptive transfer of low numbers of IL-10-producing CD25(+)CD4(+) T cells (>75% FoxP3(+)) purified from cervical lymph nodes of commensal bacteria reduced mice and in vivo neutralization of CD25(+) cells suggested the role of regulatory T cells maintaining peripheral immune homeostasis. Our data demonstrate that antibiotic modification of gut commensal bacteria can modulate peripheral immune tolerance that can protect against EAE. This approach may offer a new therapeutic paradigm in the treatment of multiple sclerosis and perhaps other autoimmune conditions.", "title": "Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis." } ]
PLAIN-3158	Egg Industry Blind Spot	[ { "docid": "MED-3780", "text": "Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.", "title": "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease" }, { "docid": "MED-2371", "text": "Background Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk. Objective To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults. Methods Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel. Results Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%; p = 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%; p < 0.01) and lowered serum total cholesterol (-18 ± 18 vs. -5 ± 21 mg/dL; p < 0.01) and LDL (-14 ± 20 vs. -2 ± 19 mg/dL; p = 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline. Conclusions Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.", "title": "Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk" }, { "docid": "MED-3789", "text": "Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.", "title": "Choline intake and risk of lethal prostate cancer: incidence and survival" }, { "docid": "MED-3786", "text": "This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.", "title": "Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria." }, { "docid": "MED-2372", "text": "BACKGROUND: Because of egg cholesterol content, reduction in egg consumption is generally recommended to reduce risk of cardiovascular disease. Recently, however, evidence has been accumulating to suggest that dietary cholesterol is less relevant to cardiovascular risk than dietary saturated fat. This randomized controlled crossover trial was conducted to determine the effects of egg ingestion on endothelial function, a reliable index of cardiovascular risk. METHODS: Forty-nine healthy adults (mean age 56 years, 40% females) underwent a baseline brachial artery reactivity study (BARS), and were assigned to two eggs or oats daily for 6 weeks in random sequence with a 4-week washout. A BARS was done at the end of each treatment phase, measuring flow-mediated vasodilation (FMD) in the brachial artery using a high-frequency ultrasound. RESULTS: FMD was stable in both egg and oat groups, and between-treatment differences were not significant (egg -0.96%, oatmeal -0.79%; p value >0.05). Six weeks of egg ingestion had no effect on total cholesterol (baseline: 203.8 mg/dl; post-treatment: 205.3) or LDL (baseline: 124.8 mg/dl; post-treatment: 129.1). In contrast, 6 weeks of oats lowered total cholesterol (to 194 mg/dl; p = 0.0017) and LDL (to 116.6 mg/dl; p = 0.012). There were no differences in body mass index (BMI), triglyceride, HDL or SBP levels between egg and oat treatment assignments. CONCLUSION: Short-term egg consumption does not adversely affect endothelial function in healthy adults, supporting the view that dietary cholesterol may be less detrimental to cardiovascular health than previously thought.", "title": "Egg consumption and endothelial function: a randomized controlled crossover trial." }, { "docid": "MED-3781", "text": "In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.", "title": "Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..." }, { "docid": "MED-3784", "text": "Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.", "title": "Choline and betaine intake and the risk of colorectal cancer in men" }, { "docid": "MED-3782", "text": "Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men.", "title": "Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival" }, { "docid": "MED-3193", "text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.", "title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma" }, { "docid": "MED-3783", "text": "Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria", "title": "Fish odour syndrome" }, { "docid": "MED-3787", "text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.", "title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma" }, { "docid": "MED-3785", "text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.", "title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites." }, { "docid": "MED-4324", "text": "BACKGROUND: Increasingly the potential harm from high cholesterol intake, and specifically from egg yolks, is considered insignificant. We therefore assessed total plaque area (TPA) in patients attending Canadian vascular prevention clinics to determine if the atherosclerosis burden, as a marker of arterial damage, was related to egg intake. To provide perspective on the magnitude of the effect, we also analysed the effect of smoking (pack-years). METHODS: Consecutive patients attending vascular prevention clinics at University Hospital had baseline measurement of TPA by duplex ultrasound, and filled out questionnaires regarding their lifestyle and medications, including pack-years of smoking, and the number of egg yolks consumed per week times the number of years consumed (egg-yolk years). RESULTS: Data were available in 1262 patients; mean (SD) age was 61.5 (14.8) years; 47% were women. Carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and with egg-yolk years. Plaque area in patients consuming <2 eggs per week (n = 388) was 125 ± 129 mm(2), versus 132 ± 142 mm(2) in those consuming 3 or more eggs per week (n = 603); (p < 0.0001 after adjustment for age). In multiple regression, egg-yolk years remained significant after adjusting for coronary risk factors. INTERPRETATION: Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease. This hypothesis should be tested in a prospective study with more detailed information about diet, and other possible confounders such as exercise and waist circumference. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Egg yolk consumption and carotid plaque." }, { "docid": "MED-4385", "text": "The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.", "title": "The influence of dietary lutein and zeaxanthin on visual performance." }, { "docid": "MED-2370", "text": "In this third installment of the series, we point out that the absence of an explicit, detailed and plausible hypothesis linking hypercholesterolemia to the events in the artery wall was probably an important reason for continuing skepticism and for failure to treat elevated blood cholesterol levels. The rapid advances in understanding of lipoprotein metabolism in the 1950s and 1960s and the application of modern cellular biology in the 1970s provided the context for a modern consensus on pathogenetic mechanisms of atherogenesis.", "title": "Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defi..." }, { "docid": "MED-3790", "text": "Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.", "title": "Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression" } ]	[ { "docid": "MED-5216", "text": "Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.", "title": "Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies" }, { "docid": "MED-2089", "text": "In this study, genotoxicity of two mouthwash products (chlorexidin, benzidamine-HCl) were investigated in the Drosophila Wing-Spot Test which makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also, to some extent, to mwh single spots. Recording of the frequency and the size of different spots is allowed for a quantitative determination of the mutagenic and recombinogenic effects. Trans-heterozygous third-instar larvae were treated at different concentrations of the mouthwash products. Chlorexidin exposure concentrations were 0.5, 1 and 2mg/ml. Benzidamine-HCl exposure concentrations were 0.38, 0.75 and 1.5mg/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. Both chlorexidin and benzidamine-HCl were genotoxic in terms of total mutations per wing at the highest doses. Survival rates of flies used in the experiments were significantly lower than those of the control group, with both mouthwash products showing toxic effects on Drosophila melanogaster larvae. Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "title": "Genotoxicity of two mouthwash products in the Drosophila Wing-Spot Test." }, { "docid": "MED-2475", "text": "Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.", "title": "The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study." }, { "docid": "MED-4980", "text": "Feasibility of fluorescence imaging technique for the detection of diluted fecal matters from various parts of the digestive tract, including colon, ceca, small intestine, and duodenum, on poultry carcasses was investigated. One of the challenges for using fluorescence imaging for inspection of agricultural material is the low fluorescence yield in that fluorescence can be masked by ambient light. A laser-induced fluorescence imaging system (LIFIS) developed by our group allowed acquisition of fluorescence from feces-contaminated poultry carcasses in ambient light. Fluorescence emission images at 630 nm were captured with 415-nm laser excitation. Image processing algorithms including threshold and image erosion were used to identify fecal spots diluted up to 1: 10 by weight with double distilled water. Feces spots on the carcasses, without dilution and up to 1: 5 dilutions, could be detected with 100% accuracy regardless of feces type. Detection accuracy for fecal matters diluted up to 1: 10 was 96.6%. The results demonstrated good potential of the LIFIS for detection of diluted poultry fecal matter, which can harbor pathogens, on poultry carcasses.", "title": "Detection of fecal residue on poultry carcasses by laser-induced fluorescence imaging." }, { "docid": "MED-4032", "text": "AIM: The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. METHODS: A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. RESULTS: The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. CONCLUSION: In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.", "title": "Oral implications of the vegan diet: observational study." }, { "docid": "MED-4747", "text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.", "title": "Hormonal growth promoting agents in food producing animals." }, { "docid": "MED-936", "text": "BACKGROUND: The contribution of ascorbate to urinary oxalate is controversial. The present study aimed to determine whether urinary oxalate and pH may be affected by vitamin C supplementation in calcium stone-forming patients. METHODS: Forty-seven adult calcium stone-forming patients received either 1 g (N=23) or 2 g (N=24) of vitamin C supplement for 3 days and 20 healthy subjects received 1 g. A 24-hour urine sample was obtained both before and after vitamin C for calcium, oxalate, magnesium, citrate, sodium, potassium, and creatinine determination. The Tiselius index was used as a calcium oxalate crystallization index. A spot fasting morning urine sample was also obtained to determine the urinary pH before and after vitamin C. RESULTS: Fasting urinary pH did not change after 1 g (5.8 +/- 0.6 vs. 5.8 +/- 0.7) or 2 g vitamin C (5.8 +/- 0.8 vs. 5.8 +/- 0.7). A significant increase in mean urinary oxalate was observed in calcium stone-forming patients receiving either 1 g (50 +/- 16 vs. 31 +/- 12 mg/24 hours) or 2 g (48 +/- 21 vs. 34 +/- 12 mg/24 hours) of vitamin C and in healthy subjects (25 +/- 12 vs. 39 +/- 13 mg/24 hours). A significant increase in mean Tiselius index was observed in calcium stone-forming patients after 1 g (1.43 +/- 0.70 vs. 0.92 +/- 0.65) or 2 g vitamin C (1.61 +/- 1.05 vs. 0.99 +/- 0.55) and in healthy subjects (1.50 +/- 0.69 vs. 0.91 +/- 0.46). Ancillary analyses of spot urine obtained after vitamin C were performed in 15 control subjects in vessels with or without ethylenediaminetetraacetic acid (EDTA) with no difference in urinary oxalate between them (28 +/- 23 vs. 26 +/- 21 mg/L), suggesting that the in vitro conversion of ascorbate to oxalate did not occur. CONCLUSION: These data suggest that vitamin C supplementation may increase urinary oxalate excretion and the risk of calcium oxalate crystallization in calcium stone-forming patients.", "title": "Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients." }, { "docid": "MED-4625", "text": "Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose. (c) 2010 Elsevier Ltd. All rights reserved.", "title": "Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women." }, { "docid": "MED-2884", "text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.", "title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women." }, { "docid": "MED-963", "text": "The public perceives that the nutritional quality of eggs produced as free range is superior to that of eggs produced in cages. Therefore, this study compared the nutrient content of free-range vs. cage-produced shell eggs by examining the effects of the laboratory, production environment, and hen age. A flock of 500 Hy-Line Brown layers were hatched simultaneously and received the same care (i.e., vaccination, lighting, and feeding regimen), with the only difference being access to the range. The nutrient content of the eggs was analyzed for cholesterol, n-3 fatty acids, saturated fat, monounsaturated fat, polyunsaturated fat, β-carotene, vitamin A, and vitamin E. The same egg pool was divided and sent to 4 different laboratories for analysis. The laboratory was found to have a significant effect on the content of all nutrients in the analysis except for cholesterol. Total fat content in the samples varied (P < 0.001) from a high of 8.88% to a low of 6.76% in laboratories D and C, respectively. Eggs from the range production environment had more total fat (P < 0.05), monounsaturated fat (P < 0.05), and polyunsaturated fat (P < 0.001) than eggs produced by caged hens. Levels of n-3 fatty acids were also higher (P < 0.05), at 0.17% in range eggs vs. 0.14% in cage eggs. The range environment had no effect on cholesterol (163.42 and 165.38 mg/50 g in eggs from caged and range hens, respectively). Vitamin A and E levels were not affected by the husbandry to which the hens were exposed but were lowest at 62 wk of age. The age of the hens did not influence the fat levels in the egg, but cholesterol levels were highest (P < 0.001) at 62 wk of age (172.54 mg/50 g). Although range production did not influence the cholesterol level in the egg, there was an increase in fat levels in eggs produced on the range.", "title": "Comparison of fatty acid, cholesterol, and vitamin A and E composition in eggs from hens housed in conventional cage and range production facilities." }, { "docid": "MED-2976", "text": "Background: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. Objectives: We assessed the association between egg intake and incident diabetes in older adults. Design: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989–2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. Results: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1–3 eggs/mo, 1–4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. Conclusion: In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.", "title": "Egg consumption and risk of type 2 diabetes in older adults" }, { "docid": "MED-5124", "text": "Background Reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Although eggs are important sources of cholesterol and other nutrients, limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality. Objectives To examine the association between egg consumption and the risk of CVD and mortality. Design Prospective cohort study of 21,327 participants from the Physicians' Health Study I. Egg consumption was assessed using a simple abbreviated food questionnaire. We used Cox regression to estimate relative risks. Results After an average follow up of 20 years, a total of 1,550 new myocardial infarction (MI), 1,342 incident strokes, and 5,169 deaths occurred in this cohort. Egg consumption was not associated with incident MI or stroke in a multivariable Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87-1.02), 1.03 (0.95-1.11), 1.05 (0.93-1.19), and 1.23 (1.11-1.36) for egg consumption of <1, 1, 2-4, 5-6, and 7+ per week, respectively, (p for trend <0.0001). This association was stronger among diabetic subjects with a 2-fold increased risk of death comparing the highest to the lowest category of egg consumption than non-diabetic subjects (HR: 1.22 (1.09-1.35) (p for interaction 0.09). Conclusions Our data suggest that infrequent egg consumption does not influence the risk of CVD and only confers a modest increased risk for total mortality in male physicians. In addition, egg consumption was positively related to mortality and such relation was stronger among diabetic subjects in this selective population.", "title": "Egg Consumption and Cardiovascular Disease and Mortality The Physicians' Health Study" }, { "docid": "MED-3774", "text": "While dehydration has well-documented negative effects on adult cognition, there is little research on hydration and cognitive performance in children. We investigated whether having a drink of water improved children's performance on cognitive tasks. Fifty-eight children aged 7-9 years old were randomly allocated to a group that received additional water or a group that did not. Results showed that children who drank additional water rated themselves as significantly less thirsty than the comparison group (p=0.002), and they performed better on visual attention tasks (letter cancellation, p=0.02; spot the difference memory tasks, ps=0.019 and 0.014).", "title": "Should children drink more water?: the effects of drinking water on cognition in children." }, { "docid": "MED-1884", "text": "We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.", "title": "Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge." }, { "docid": "MED-2849", "text": "Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus. However, their association with gestational diabetes mellitus (GDM) has not been evaluated. The authors assessed such associations in both a prospective cohort study (1996–2008; 3,158 participants) and a case-control study (1998–2002; 185 cases, 411 controls). A food frequency questionnaire was used to assess maternal diet. Multivariable models were used to derive relative risks and 95% confidence intervals. Compared with no egg consumption, adjusted relative risks for GDM were 0.94, 1.01, 1.12, 1.54, and 2.52 for consumption of ≤1, 2–3, 4–6, 7–9, and ≥10 eggs/week, respectively (P for trend = 0.008). Women with high egg consumption (≥7/week) had a 1.77-fold increased risk compared with women with lower consumption (95% confidence interval (CI): 1.19, 2.63). The relative risk for the highest quartile of cholesterol intake (≥294 mg/day) versus the lowest (<151 mg/day) was 2.35 (95% CI: 1.35, 4.09). In the case-control study, the adjusted odds ratio for consuming ≥7 eggs/week versus <7 eggs/week was 2.65 (95% CI: 1.48, 4.72), and the odds of GDM increased with increasing cholesterol intake (P for trend = 0.021). In conclusion, high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM.", "title": "Risk of Gestational Diabetes Mellitus in Relation to Maternal Egg and Cholesterol Intake" }, { "docid": "MED-2975", "text": "BACKGROUND: Although egg consumption has been associated with elevated plasma levels of cholesterol and triglyceride and with risk of cardiovascular disease in some populations, epidemiologic studies on egg consumption and the risk of diabetes are extremely sparse, particularly in the Chinese population. METHOD: Data from a household survey in the year 2002 among 2849 adults aged ≥20 y from a nationally representative sample in Jiangsu Province, China, were used. Dietary information was assessed by a validated food frequency questionnaire and 3 d weighed food records. Fasting blood specimens were collected. RESULTS: After the adjustment for age, total calorie intake, education, smoking, family history of diabetes, and sedentary activity, egg consumption was significantly and positively associated with diabetes risk, particularly in women. The odds ratios (OR) (95% CI) of diabetes associated with egg consumption <2/wk, 2-6/wk, and ≥1/d in the total sample were 1.00, 1.75, 2.28 (1.14-4.54), respectively (P for trend 0.029). Corresponding ORs (95% CI) in women were 1.00, 1.66, and 3.01 (1.12, 8.12), respectively (P for trend 0.022). Additional adjustment of body mass index attenuated the association, but it remained significant. There was a similar, however, not statistically significant association in men. In addition, plasma triglyceride and total cholesterol levels were significantly higher in women who consumed ≥2 eggs/wk than those who consumed eggs less often. CONCLUSION: Egg consumption was positively associated with the risk of diabetes among the Chinese, particularly in women. Copyright Â© 2011 Elsevier Inc. All rights reserved.", "title": "Egg consumption and the risk of diabetes in adults, Jiangsu, China." }, { "docid": "MED-1889", "text": "Consumption of eggs for a long period was shown to result in hypercholesterolemia and is generally restricted for this reason. In the present study we analyzed the effect of eggs consumption for 3 weeks on lipoprotein atherogenicity. Consumption of 2 eggs per day with the meals, for 3 weeks resulted in a minor elevation in plasma glucose and urea concentrations. Plasma cholesterol concentration increased by 11% (p < 0.05) as a result of increased plasma low-density lipoprotein (LDL) cholesterol levels. Plasma triglycerides decreased by 13% (p < 0.01), but there were no significant alterations in plasma apolipoproteins A-I or B-100 concentrations. Plasma high-density lipoprotein (HDL) cholesterol decreased by 11% (p < 0.05). There was a 13% reduction, though not significant, in the cholesterol efflux from J-774 A.1 macrophages by HDL that was derived after eggs consumption in comparison to HDL that was obtained at baseline. The susceptibility of plasma [using 100 mM of 2,2' azobis 2-amidinopropane (AAPH)] as well as that of LDL (using 10 microM of copper ions) to lipid peroxidation was increased by 42% and 34%, respectively, as measured by the thiobarbituric acid reactive substance (TBARS) assay (p < 0.01). Kinetic analysis of LDL oxidation by copper ions revealed a 37% reduction in the lag time required for the initiation of LDL oxidation after 3 weeks of eggs consumption. The total plasma fatty acids concentration increased from 2.2 +/- 0.5 to 3.2 +/- 0.6 mg/ml. The plasma antioxidants, vitamin E and carotenoids were not significantly affected by eggs consumption. We conclude that eggs consumption, in addition to its hypercholesterolemic effect, increases plasma and LDL oxidizability, a phenomenon which was shown to enhance the progression of atherosclerosis. The atherogenic properties may contribute to the accelerated atherosclerosis prevalent in populations with high cholesterol intake.", "title": "Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation." }, { "docid": "MED-2977", "text": "OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.", "title": "Egg Consumption and Risk of Type 2 Diabetes in Men and Women" }, { "docid": "MED-4892", "text": "OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.", "title": "Egg Consumption and Risk of Type 2 Diabetes in Men and Women" }, { "docid": "MED-4429", "text": "Epidemiological studies show that poultry meat and eggs are important sources for consumers' exposure to pathogens such as Salmonella and Campylobacter. There is a focus in many countries to reduce the level of human illness from food-borne pathogens. Reduction of the prevalence of contaminated poultry meat or eggs is one major area of focus. The other is risk communication to the consumer, where information aimed at changing the food preparation behaviour has been utilised as a risk management tool. The efficacy of messages such as 'cook poultry meat and eggs thoroughly' or 'wash your hands' will depend both on the ability to change consumer behaviour as well as where the risk can best be mitigated. In order to prioritise what message should be given to the consumer, the relative contribution of different exposure pathways finally leading to ingestion of the pathogens and resulting in illness needs to be known. It is important to know whether cross-contamination events or undercooking are the greatest risk lurking in consumers' kitchens. A review of studies looking at the location of pathogens in food products has been performed and data regarding internal and external (surface) contamination of poultry meat with Salmonella spp. and Campylobacter jejuni and C. coli is presented. In the case of eggs, data on internal contamination with Salmonella and for contamination of egg shells with Salmonella and Campylobacter are discussed. The results from published risk assessments for these pathogen-food commodity combinations have been evaluated and conclusions regarding the relative risk of internal and external contamination of poultry meat and eggs were drawn. In conclusion, cross-contamination events from activities such as use of the same cutting board for chicken meat and salad without intermediate cleaning or spreading of pathogens via the kitchen environment seem to be of greater importance than the risk associated with undercooking of poultry meat or eggs. Risk management options are discussed against the background of risk communication strategies used in different countries.", "title": "Cross-contamination versus undercooking of poultry meat or eggs - which risks need to be managed first?" }, { "docid": "MED-4175", "text": "In this study, 10 perfluorochemicals (PFCs) were measured in meat, meat products, and eggs, and in indoor dust, collected in China. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the most frequently detected PFCs in these samples. Mean concentrations of PFOS and PFOA in foodstuffs were in the range of 0.05-1.99 ng/g fresh wt and 0.06-12.5 ng/g fresh wt, respectively. The mean concentrations of PFOA, perfluoroheptanoic acid (PFHpA), and PFOS in indoor dust were 205, 14.0, and 4.86 ng/g, dry wt, respectively. The estimated daily intake of PFOS and PFOA from meat, meat products and eggs (EDI(meat&eggs)) ranged from 6.00 to 9.64 ng/d and from 254 to 576 ng/d, respectively, when the values below the limit of quantitation (LOQ) were assigned as 0, and from 8.80 to 15.0 ng/d and from 255 to 577 ng/d, respectively, when the values below the LOQ were set at 1/2LOQ. The EDI(meat&eggs) of PFOS and PFOA increased with increasing family income. The estimated daily intake of PFOS and PFOA through inhalation of dust (EDI(dust)) ranged from 0.23 to 0.31 ng/d and from 9.68 to 13.4 ng/d, respectively. The daily intakes of PFOS and PFOA from the consumption of meat, meat products, and eggs, and from dust ingestion, as calculated from our samples in this study, were compared with estimated daily intake of PFCs reported from the concentrations in drinking water, fish and seafood from China. Our calculations indicate that dietary sources (EDI(dietary)) account for the overwhelming proportion of (>99% for PFOS and 98% for PFOA) total daily intake (TDI) in adults. The analyzed foodstuffs (meat, meat products, and eggs) were not the major contributors to dietary exposure to PFOS, whereas, meat was the primary contributor to dietary exposure to PFOA.", "title": "Perfluorochemicals in meat, eggs and indoor dust in China: assessment of sources and pathways of human exposure to perfluorochemicals." }, { "docid": "MED-2973", "text": "OBJECTIVE: Type 2 diabetes mellitus appears to involve an interaction between susceptible genetic backgrounds and environmental factors including highly calorific diets. As it is important to identify modifiable risk factors that may help reduce the risk of type 2 diabetes mellitus, the aim of the present study was to determine the association between egg consumption and the risk of type 2 diabetes mellitus. DESIGN: A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes mellitus. The odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were calculated by conditional logistic regression. SETTING: A case-control study in a Lithuanian out-patient clinic was performed in 2001. SUBJECTS: A total of 234 cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls free of the disease. RESULTS: Variables such as BMI, family history of diabetes, cigarette smoking, education, morning exercise and plasma TAG level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the odds ratio by more than 10 % in any exposure category. After adjustment for possible confounders more than twofold increased risk of type 2 diabetes mellitus was determined for individuals consuming 3-4·9 eggs/week (OR = 2·60; 95 % CI 1·34, 5·08) and threefold increased risk of the disease was determined for individuals consuming ≥5 eggs/week (OR = 3·02; 95 % CI 1·14, 7·98) compared with those eating <1 egg/week. CONCLUSIONS: Our data support a possible relationship of egg consumption and increased risk of type 2 diabetes mellitus.", "title": "Egg consumption and the risk of type 2 diabetes mellitus: a case-control study." }, { "docid": "MED-1956", "text": "The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the \"chick edema factor\" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.", "title": "Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine." }, { "docid": "MED-4741", "text": "BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.", "title": "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay." }, { "docid": "MED-2374", "text": "OBJECTIVES: To assess the dose-response relationship between egg consumption and the risk of cardiovascular diseases (CVD) and diabetes. METHODS: We systematically searched MEDLINE database through December 2012. Fixed- or random-effects model was used to pool the relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses was performed to explore the potential sources of heterogeneity. Weighted linear regression model was used to estimate the dose-response relationship. RESULTS: Fourteen studies involving 320,778 subjects were included. The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02-1.38), 1.83 (95% CI 1.42-2.37), 1.68 (95% CI 1.41-2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03-1.10), 1.40 (95% CI 1.25-1.57), 1.29 (95% CI 1.21-1.37), respectively. Subgroup analyses showed that population in other western countries have increased CVD than ones in USA (RR 2.00, 95% CI 1.14 to 3.51 vs 1.13, 95% CI 0.98 to 1.30, P = 0.02 for subgroup difference). CONCLUSIONS: Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis." }, { "docid": "MED-1890", "text": "BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological s searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.", "title": "Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis." }, { "docid": "MED-1174", "text": "We used a novel study design to measure dietary organophosphorus pesticide exposure in a group of 23 elementary school-age children through urinary biomonitoring. We substituted most of children’s conventional diets with organic food items for 5 consecutive days and collected two spot daily urine samples, first-morning and before-bedtime voids, throughout the 15-day study period. We found that the median urinary concentrations of the specific metabolites for malathion and chlorpyrifos decreased to the nondetect levels immediately after the introduction of organic diets and remained nondetectable until the conventional diets were reintroduced. The median concentrations for other organophosphorus pesticide metabolites were also lower in the organic diet consumption days; however, the detection of those metabolites was not frequent enough to show any statistical significance. In conclusion, we were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agricultural production. We also concluded that these children were most likely exposed to these organophosphorus pesticides exclusively through their diet. To our knowledge, this is the first study to employ a longitudinal design with a dietary intervention to assess children’s exposure to pesticides. It provides new and persuasive evidence of the effectiveness of this intervention.", "title": "Organic Diets Significantly Lower Children’s Dietary Exposure to Organophosphorus Pesticides" }, { "docid": "MED-751", "text": "BACKGROUND AND AIMS Although dietary fats and cholesterol have previously been associated with risk of cardiovascular disease (CVD) in middle aged populations, less is known among older adults. The purpose of this study was to determine the association between dietary fats, cholesterol, and eggs and CVD risk among community-dwelling adults aged 70–79 in the Health, Aging and Body Composition Study. METHODS AND RESULTS Diet was assessed using an interviewer-administered 108-item food frequency questionnaire (n=1,941). CVD events were defined as a confirmed myocardial infarction, coronary death, or stroke. Relative rates of CVD over 9 years of follow-up were estimated using Cox proportional hazards models. During follow-up, there were 203 incident cases of CVD. There were no significant associations between dietary fats and CVD risk. Dietary cholesterol (HR (95% CI): 1.47 (0.93, 2.32) for the upper vs. lower tertile; P for trend, 0.10) and egg consumption (HR (95% CI): 1.68 (1.12, 2.51) for 3+/week vs. <1/week); P for trend, 0.01) were associated with increased CVD risk. However, in subgroup analyses, dietary cholesterol and egg consumption were associated with increased CVD risk only among older adults with type 2 diabetes (HR (95% CI): 3.66 (1.09, 12.29) and 5.02 (1.63, 15.52), respectively, for the upper vs. lower tertile/group). CONCLUSIONS Dietary cholesterol and egg consumption were associated with increased CVD risk among older, community-dwelling adults with type 2 diabetes. Further research on the biological mechanism(s) for the increased CVD risk with higher dietary cholesterol and frequent egg consumption among older adults with diabetes is warranted.", "title": "Dietary Fat and Cholesterol and Risk of Cardiovascular Disease in Older Adults: the Health ABC Study" }, { "docid": "MED-4676", "text": "A widespread misconception has been developing among the Canadian public and among physicians. It is increasingly believed that consumption of dietary cholesterol and egg yolks is harmless. There are good reasons for long-standing recommendations that dietary cholesterol should be limited to less than 200 mg/day; a single large egg yolk contains approximately 275 mg of cholesterol (more than a day’s worth of cholesterol). Although some studies showed no harm from consumption of eggs in healthy people, this outcome may have been due to lack of power to detect clinically relevant increases in a low-risk population. Moreover, the same studies showed that among participants who became diabetic during observation, consumption of one egg a day doubled their risk compared with less than one egg a week. Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries. Patients at risk of cardiovascular disease should limit their intake of cholesterol. Stopping the consumption of egg yolks after a stroke or myocardial infarction would be like quitting smoking after a diagnosis of lung cancer: a necessary action, but late. The evidence presented in the current review suggests that the widespread perception among the public and health care professionals that dietary cholesterol is benign is misplaced, and that improved education is needed to correct this misconception. Résumé Une idée fausse et généralisée se répand au sein du public canadien et des médecins, qui pensent de plus en plus que la consommation de cholestérol alimentaire et de jaunes d’œuf est inoffensive. Les recommandations de longue date qui préconisent de limiter le cholestérol alimentaire à moins de 200 mg/jour reposent sur de bonnes raisons. Un seul gros jaune d’œuf contient environ 275 mg de cholestérol (plus que la portion quotidienne de cholestérol). Même si certaines études ont démontré que la consommation d’œufs n’est pas nuisible chez les personnes en santé, ce résultat peut découler de l’absence de capacité à déceler des augmentations pertinentes sur le plan clinique au sein d’une population à faible risque. De plus, les mêmes études ont révélé que chez les participants devenus diabétiques pendant la période d’observation, la consommation d’un œuf par jour doublait leur risque par rapport à la consommation de moins d’un œuf par semaine. Le régime ne vise pas à éviter le cholestérol, mais surtout les effets postprandiaux du cholestérol, des gras saturés, du stress oxydant et de l’inflammation. Le fait de se concentrer à tort sur les lipides à jeun occulte trois enjeux. Le cholestérol alimentaire accroît la susceptibilité des lipoprotéines à faible densité à l’oxydation, accroît la lipémie postprandiale et potentialise les effets secondaires des graisses saturées alimentaires. Le cholestérol alimentaire, y compris les jaunes d’œuf, est nuisible pour les artères. Les patients vulnérables aux maladies cardiovasculaires devraient limiter leur consommation de cholestérol. Le fait d’arrêter de consommer des jaunes d’œuf après un accident vasculaire cérébral ou un infarctus du myocarde s’apparenterait à arrêter de fumer après un diagnostic de cancer du poumon : c’est un geste nécessaire, mais entrepris tardivement. D’après les données probantes présentées dans la présente analyse, la perception généralisée du public et des professionnels de la santé selon laquelle le cholestérol alimentaire est un mal bénin est une idée fausse, et une meilleure information s’impose pour la corriger.", "title": "Dietary cholesterol and egg yolks: Not for patients at risk of vascular disease" }, { "docid": "MED-2221", "text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.", "title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?" } ]
5ae2a8bf554299492dc91c40	For which rock band did Mark Evans play bass guitar on the band's third LP released in Australia and in Europe in 1976?	[ { "docid": "9327283", "text": "Dirty Deeds Done Dirt Cheap is an album by Australian hard rock band AC/DC. It was the band's third LP released in Australia and in Europe in 1976 but was not released in the US until 1981, more than one year after Bon Scott's death. All songs were written by Angus Young, Malcolm Young and Bon Scott.", "title": "" }, { "docid": "1943156", "text": "Mark Whitmore Evans (born 2 March 1956) is an Australian bass guitarist for the Australian rock band Rose Tattoo who was an early member of hard rock band AC/DC from March 1975 to June 1977. His playing featured on their albums \"T.N.T\", \"High Voltage\", \"Dirty Deeds Done Dirt Cheap\", \"Let There Be Rock\" and \"'74 Jailbreak\". Evans has played for numerous other groups, sometimes on lead guitar, including Finch (a.k.a. Contraband), Cheetah, Swanee, Heaven and The Party Boys. Evans' autobiography, \"Dirty Deeds: My Life Inside/Outside of AC/DC\" was released in December 2011.", "title": "" } ]	[ { "docid": "8700109", "text": "Rabbit (originally, The Cherries) were an Australian glam rock band from Newcastle, which formed in 1973 by Jim Porteus on bass guitar, Phil Screen on drums and Mark Tinson on guitar and vocals. In October 1974 they were joined by Dave Evans (ex-AC/DC) on lead vocals. The group relocated to Sydney and released two albums, \"Rabbit\" (1975) and \"Too Much Rock n Roll\" (1976), before disbanding in late 1977. Porteus, Screen and Tinson returned to Newcastle where they formed a hard rock band, Heroes, with Peter De Jong on guitar and vocals. They issued a self-titled album in October 1980 and disbanded in 1982.", "title": "" }, { "docid": "43445391", "text": "The Peep Tempel is a punk rock band from Melbourne, Australia. The band's line-up includes Blake Scott (vocals, guitar), Steven Carter (drums) and Stewart Rayner (bass guitar). After releasing two singles The Peep Tempel released their debut LP \"The Peep Tempel\" in February 2012, an EP \"Modern Professional\" in June 2013 and their second LP \"Tales\" in October 2014 through Melbourne imprint Wing Sing. The third The Peep Tempel LP \"Joy\" was released in October 2016.", "title": "" }, { "docid": "4642618", "text": "AC/DC are an Australian hard rock band formed by guitarist brothers Angus and Malcolm Young in 1973. Originally featuring vocalist Dave Evans, bassist Larry Van Kriedt and drummer Colin Burgess, after a number of lineup changes the band settled with Bon Scott on vocals, Mark Evans on bass guitar and Phil Rudd on drums, and released five albums (two limited to Australia) between 1974 and 1977. Due to continuing clashes with lead guitarist Angus Young, Evans was later fired from the band shortly after the release of \"Let There Be Rock\", although \"musical differences\" was the official reason given for his departure. Cliff Williams was brought in as his replacement.", "title": "" }, { "docid": "8216463", "text": "The Blitz is the eighth studio album by the Swiss hard rock band Krokus, released in August 1984. It became a gold album in the United States. The band hit the Billboard Hot 100 with \"Midnite Maniac\" from that album and became the first Swiss act to do so. While preparing to record it, Patrick Mahassen had been tapped to join the band on guitar, Mark Kohler having switched to bass. Mahassen did not join, and the album was recorded as a quartet; Andy Tanas played bass on the subsequent tour.", "title": "" }, { "docid": "22653988", "text": "Verona or vrn, is a rock band formed in Punto Fijo at the end of 2000, by Chevy (guitars and vocals), Atari (guitar and backing vocals), Paúl Jatem (bass guitar) and Eduardo (drums). In 2001, they recorded their first EP, \"Delirium\", which included earlier recordings from Chevy. Paúl left the band in 2003 and was replaced by Adolfo Alcala. Alcala was credited with the composition of Verona's first LP, \"Summer Consequence\", but he left before its recording. He was replaced by Ray Diaz in December 2003. In May 2004, Verona released \"Summer Consequence\". The band, with the same members, released its second LP, \"Anywhere\" in March 2008.", "title": "" }, { "docid": "1689029", "text": "INXS is Australian rock band INXS's first album. It was released on Deluxe Records in Australia on 13 October 1980. The band recorded the album in midnight to dawn sessions during 1979 to 1980 after performing, on average, two gigs a day at local pubs around Sydney. All tracks were credited to band members, Garry Gary Beers (bass guitar and double bass); brothers Andrew (keyboards and guitar), Jon (drums, keyboards) and Tim Farriss (lead guitar); Michael Hutchence (lead vocals); and Kirk Pengilly (guitar, saxophone and backing vocals). The album was co-produced by the band and Duncan McGuire (ex-Ayers Rock). It spawned the single, \"Just Keep Walking\" (September 1980), which became their first Australian Top 40 hit. \"INXS\" peaked in the Top 30 of the related Kent Music Report Albums Chart. The album did not appear internationally until 1984.", "title": "" }, { "docid": "15957743", "text": "The Bamboos were a swamp and alternative rock band from Collie, Western Australia which formed in 1984 by mainstays Mark Gelmi on bass guitar and Craig Hallsworth on guitar and vocals. They relocated to Perth by the following year and were joined by Greg Hitchcock (ex-The Go-Starts, Graverobbers) on guitar, and by Shakir Pichler (ex-The Kryptonics) on drums in 1986 who was replaced by Russell Hopkinson in the next year. The Bamboos released an album, \"Rarer than Rockinghorse Shit\" and an EP, \"Born Killer\", before they disbanded in late 1987.", "title": "" }, { "docid": "2106766", "text": "Bedhead was an American, Texas-based indie rock band, active from 1991 to 1998. Members consisted of Matt and Bubba Kadane (vocals and guitar), Tench Coxe (guitar), Kris Wheat (bass), and Trini Martinez (drums). The band released several EPs and three LPs on Trance Syndicate, touring intermittently. Bedhead's music was generally subdued, with three electric guitars and one electric bass guitar over sung or spoken vocals. Allmusic dubbed the group \"the quintessential indie rock band,\" and \"Tiny Mix Tapes\" gave their final album \"Transaction de Novo\" a perfect 5/5 score.", "title": "" }, { "docid": "5683738", "text": "The Cold was a new wave band that formed in New Orleans in 1979. The band was hugely popular in its home city and throughout the southeastern U.S. during its existence, but did not find national success. The members of The Cold were Barbara Menendez (vocals and keyboards), Vance DeGeneres (bass), Chris Luckette (drums), Kevin Radecker (guitar) and Bert Smith (guitar). Influenced by British punk bands as well as American act Blondie, the band released several independent singles between 1980 and 1982, then split up. They reunited in 1984 for an LP and new single release, and released another album in 1985. In 1997, a compilation of their early singles entitled \"Three Chord City\" was released. The band reunited for some live performances in 1999 and 2001. In 2005 a CD of outtakes from the band's original incarnation was released.", "title": "" }, { "docid": "39743250", "text": "Corrupted Ideals is a punk rock band from Long Beach, California formed in 1988. The band's early line-up, which appeared on their first full-length LP, Join the Resistance, included Paul Kelly and Mike Nigro, on vocals and guitar, respectively. They wrote most of the material together, with Mike writing most of the music, and Paul contributing most of the lyrics. The band's second release, Anti-Generation, came with a lineup change, including Pete \"Action Man\" Archer on bass, and Anthony Guarino on drums. Nicky Garratt also played guitar on portions of Anti-Generation, including the CI cover of the UK Subs, \"Telephone Numbers.\" Pete and Anthony played in another band together in the mid-1980s, called Violent Outrage (a band that played with Corrupted Ideals regularly in the mid-late 1980s. This line up changed slightly a week before touring the Western US, with Pete moving to bass in the Stitches (who were opening for Corrupted Ideals on tour), and Anthony moving to bass, as the band was able to recruit celebrated punk rock drummer Sean Antillon to play drums. Sean is known best for playing drums for the Weirdos, but also has (or is currently) played for the Gears, the Stains, the Skulls, and many other early LA bands who reformed. Currently, Corrupted Ideals lineup includes Steve Swailes of the Hitchhikers playing guitar, Paul Kelly on vocals, Anthony Guarino playing bass, and Sean Antillon on drums.", "title": "" }, { "docid": "20234003", "text": "The Vampire Lovers, also styled as Vampyre Lovers or Vampire Lovers, were a Brisbane punk rock group which formed in 1982 in Queensland, Australia. Original band members were Axle \"Axe Babe\" Conrad on vocals, Brendan Kibble on guitar, Shane Cooke on bass guitar, Matt \"Nasty\" Le Noury on guitar and Dave Chamberlain on drums. Other members included guitarist Jason Shepherd; and drummer, Ziggy Staten. Initially the group existed from 1982 to 1984 and then reformed in 1988 to disband finally in 1990. In 1983 their first single, \"Buzzsaw Popstar\", brought greater recognition from the Australia alternative rock fans. In 1991 they released a mini-LP, \"Acid Commandos from Planet Fuzz\", a year after they had disbanded.", "title": "" }, { "docid": "37715210", "text": "Citizens! are a British indie rock band from London, formed in the summer of 2010. The band consists of Tom Burke (vocals), Thom Rhoades (guitar), Martyn Richmond (bass), Lawrence Diamond (keyboards) and Mike Evans (drums). Their debut album \"Here We Are\" was released by Kitsuné on 28 May 2012 in the UK / Europe and on 9 October 2012 in North America.", "title": "" }, { "docid": "489387", "text": "Third Eye Blind is an American rock band formed in San Francisco in 1993. The songwriting duo of Stephan Jenkins and Kevin Cadogan signed the band's first major label recording contract with Elektra Records in 1996, which was later reported as the largest publishing deal ever for an unsigned artist. The band released their self-titled album, \"Third Eye Blind\", in 1997, with the band largely consisting of Jenkins (lead vocals, rhythm guitar), Cadogan (lead guitar), Arion Salazar (bass guitar), and Brad Hargreaves (drums). Shortly after the release of the band's second album in 1999, \"Blue\", with the same line-up, Cadogan was released from the band under controversial circumstances.", "title": "" }, { "docid": "35253160", "text": "Evans The Death are an English indie rock band formed in London in 2011. The band consists of brothers Dan and Olly Moss (guitars), Katherine Whitaker (vocals), Daniel Raphael (bass) and James Burkitt (drums). They have released three albums.", "title": "" }, { "docid": "42217002", "text": "Bad Dreems (stylised as Bad//Dreems) are an \"outsider rock\" band from Adelaide, South Australia. The band consists of Ben Marwe (Vocals/Guitar), Alex Cameron (Guitar), James Bartold (Bass), and Miles Wilson (Drums). The band released their debut EP titled \"Badlands\" in August 2013. They released their debut album \"Dogs at Bay\" on 21 August 2015 with legendary Australian producer Mark Opitz (INXS, Cold Chisel, the Angels).", "title": "" }, { "docid": "20392122", "text": "Radiohead, an alternative rock band from Abingdon, Oxfordshire, have had concerts and other live performances in Europe, North America, Australia, Asia and South America. The band's line-up has been constant since its founding, consisting of Thom Yorke (vocals and guitar), Jonny Greenwood (guitar), Ed O'Brien (guitar), Colin Greenwood (bass guitar), and Phil Selway (drums). The role that each band member plays during performances has changed dramatically throughout the band's history.", "title": "" }, { "docid": "25470724", "text": "My Education is an American instrumental post-rock band from Austin TX. They create cinematic and psychedelic compositions blending intense droning guitars with melodic viola. The core of the band is two guitars, bass, drums, and viola, although they do play with violins, keyboards and vibes at times. They are currently on Golden Antenna Records, a label based in Hessen, Germany, who released the band's latest LP A Drink for All My Friends in March 2013.", "title": "" }, { "docid": "27717184", "text": "Pollyanna were an Australian alternative rock band that came to prominence in the mid-1990s with their brand of noisy indie guitar pop. Formed in Sydney, (as Blue Trike, they changed their name on their 13th gig to Pollyanna) Australia in 1993, the original Pollyanna line-up was Andrea Croft (vocals/guitar, but left prior to recording) Matt Handley (vocals/guitar), Maryke Stapleton (bass), and Serge Luca (drums). They released 2 EP's, numerous singles and 4 LP's. The band went into an indefinite hiatus in 2002. (Matt and Andrea had previously been in another band - Catherine Wheel - together. 1 EP - Self Portraits)", "title": "" }, { "docid": "44175543", "text": "Iguana Lovers is an Argentine rock band that formed in 1990 in west Buenos Aires, Argentina, by Ariel Soriano (guitars and vocals), Ivan Mirabal (guitars)and Javier Accossatto (bass). They are currently playing with Gabriel Diederle (tambourine and machines) and Alfredo García Kalb (drums) The band continues today as it has since 1990 and released four LP's and nine EP's.", "title": "" }, { "docid": "15999225", "text": "Finch were an Australian hard and pub rock band, initially forming as Stillwater in 1972. By 1973 they had changed their name with the line-up of Peter McFarlane on drums, Owen Orford on lead vocals, Bob Spencer on lead guitar, and Tony Strain on bass guitar. They won a 2SM/Pepsi Pop Poll, earning a contract with Picture Records to release their debut single, \"And She Sings\" in January 1974. Their first album, \"Thunderbird\", appeared in May 1976. In March of the following year Spencer left to join Skyhooks and the group went through various line-ups to settle with McFarlane and Orford joined by Mark Evans (ex AC/DC) on bass guitar. Their second album, \"Nothing to Hide\", was issued in March 1978. Upon attempting to enter the international market they changed their name to Contraband by October that year. They issued a self-titled album in May of the next year but disbanded later in 1979.", "title": "" }, { "docid": "26488540", "text": "Eighty-three songs are included in \"Rock Band 3\", a 2010 music video game developed by Harmonix, published by MTV Games and distributed by Electronic Arts. The game, the third main title in the \"Rock Band\" series, was released in October 2010 for the Xbox 360, PlayStation 3, Wii, and Nintendo DS. \"Rock Band 3\" allows one to seven players to simulate the playing of rock music by providing the players with peripherals modeled after musical instruments. These include a guitar peripheral for lead guitar and bass gameplay, a drum kit peripheral, a keyboard peripheral, and up to three microphones. \"Rock Band 3\" is the first game in the series to include a \"Pro\" mode, which allows players to use more realistic peripherals to play the game's songs note-for-note as they would be played on an actual instrument.", "title": "" }, { "docid": "577187", "text": "The Mark of Cain (also seen as the initialism, TMOC) are a hard rock, alternative metal band from Adelaide, South Australia. Their style has been likened to that of Helmet and Rollins Band, yet this band pre-dates both groups and was influenced by the early work of Joy Division, Big Black and United States hardcore groups. The Mark of Cain were formed in mid-1984 by brothers, John (guitar) and Kim Scott (bass guitar), with Rod Archer on vocals and Gavin Atkinson playing drums. Before long, Archer had left the group and John Scott took on the lead vocal role and the group has remained a trio ever since. The Scotts have been the core of the band which has featured 15 different drummers. Since January 2001, former Helmet member John Stanier has been their drummer; he is also concurrently with Tomahawk and Battles. Australian musicologist, Ian McFarlane, described the group's sound as \"Gloomy, monotonous vocals and bleak slabs of metallic guitar did battle over a lurching rhythm section to arrive at a harsh sound.\" Rod Archer died on 26 February 2016.", "title": "" }, { "docid": "32393256", "text": "Kentucky Blue Collar Band are an American country rock band. They were founded in 2004 deep in the foothills of Eastern Kentucky as the Blue Collar Band, composed of Goble Cantrell (rhythm guitar, vocals) and Mark Rohan (drums) along with Don Hayes (lead guitar) and Dean Ball (bass guitar). After discovering that another band already existed in Louisville, Kentucky with the name \"Blue Collar Band\", the band added \"Kentucky\" to its name and thus became the Kentucky Blue Collar Band. The band began performing as the Kentucky Blue Collar Band in 2006, adding Marc Currens as bass guitarist and harmony vocalist in 2008. With the release of their debut album \"Rockin' the Road\" in 2006 with independent record label Huba Records, the band garnered a good rotation of local radio play. Their second album \"Long Hard Road\", released in 2009, fared much better and was widely played, including winning song of the month in May 2009 on a Texas radio station, Hoss the Boss with DJ Don Cudd, as well as coming in fourth for song of the year on that same station's yearly contest for 2009, setting an all-time record at that point for most fan votes of any one song in the history of the contest. The band released their third album \"Evolution\" on March 15, 2011, with that album still working its way into and up the charts.", "title": "" }, { "docid": "1087827", "text": "Cake Like was an all-female indie rock band based in New York City. Its members were bassist and lead singer Kerri Kenney, drummer Jody Seifert, and vocalist and guitarist Nina Hellman. The band came together in 1993 when Kenney and Hellman met at New York University's Experimental Theater Wing, decided to form a band, and were joined by Hellman's roommate Seifert. The members had never played music before and so developed their own unique style. Their songs often play out like poetry set to erratic guitar-rock. They soon attracted the attention of John Zorn, who signed the band to his Avant Records label, which released their first LP. Ric Ocasek, formerly of The Cars, produced their follow-up EP. Subsequently, Neil Young signed the band to his Vapor Records label, which released their second and third LPs.", "title": "" }, { "docid": "1158581", "text": "Apple were a British psychedelic rock band. The band was founded in Cardiff in 1968 by Rob Ingram on guitar and Jeff Harrad on bass. They released a single LP in 1969, titled \"An Apple a Day\". The album was a commercial failure, and the band ceased to exist shortly after its release. However, during the subsequent years several tracks from the LP, most notably \"The Otherside\" by Harrad, were dubbed classics of British psychedelic rock by critics, making \"An Apple a Day\" one of the most sought-after British psychedelic rarities.", "title": "" }, { "docid": "32419031", "text": "The Clash were a punk rock band formed in 1976 initially consisting of Joe Strummer (lead vocals, guitar), Mick Jones (vocals, lead guitar), Paul Simonon (bass guitar), Keith Levene (guitar) and Terry Chimes (drums and percussion). Levene was dismissed in September 1976 and went on to form Public Image Ltd. Terry Chimes performed intermittently as drummer for the first year of the band's existence, playing on the debut album. Topper Headon was recruited in May 1977 as the band's permanent drummer, forming the classic Clash line-up which would remain together until 1982.", "title": "" }, { "docid": "16295671", "text": "Admonish is a Swedish black metal band formed in 1994. They were one of the first bands in the Christian black metal movement and the first Christian black metal group in Sweden. While the band did not release anything until 2005, the magazine \"Metal Hammer\" called Admonish \"One of the leading Christian black metal bands\" in a 1990s issue which focused on black metal. In 2006 Admonish achieved some mainstream notice when the twins Emil (guitar) and Jonas Karlsson (bass) both appeared on the MTV Europe show \"Pimp My Ride International\" on October 6. On that show, in which their car was modified, the twins advertised their band and Admonish's music was played. The former Admonish member Per Sundberg was also a guitar-player in Crimson Moonlight.", "title": "" }, { "docid": "5833086", "text": "Flour is an American band. Flour is the nickname of Minneapolis musician Pete Conway who wrote songs and played bass guitar in the bands Rifle Sport and Breaking Circus until the mid-1980s. He released four solo albums on Touch and Go Records from 1988 to 1994 on which he plays most of the instruments himself. Flour toured as a live band twice with a lineup that featured ex-Big Black guitarist Steve Albini on bass and former Breaking Circus percussionist Todd Trainer on drums before they went on to form the band Shellac. Flour's solo recordings feature the drum machine sound characteristic of Big Black and toyed with by many other independent rock bands in the Midwest during that time period. Flour's third solo album \"Machinery Hill\" was described by Allmusic' s Richard Foss as \"an oddball masterpiece of grinding guitar, fluid bass, hammering drums, and very creative ideas\".", "title": "" }, { "docid": "969510", "text": "Lazer Guided Melodies is the debut studio album by English space rock band Spiritualized. The album was recorded by the inaugural line up of the band, consisting of Jason Pierce (vocals, guitars), Mark Refoy (guitars), Will Carruthers (bass), Jonny Mattock (drums) and Kate Radley (keyboards) from 1990 to 1991, and mixed by Pierce in London in January 1992. The album was first released on Dedicated Records in March 1992, on cassette, Compact Disc and Vinyl (2 x LP, with initial copies containing an additional free 7\").", "title": "" }, { "docid": "19164317", "text": "The Phantom Band are a Scottish indie rock band based in Glasgow, consisting of Duncan Marquiss (guitar), Gerry Hart (bass), Andy Wake (keyboards), Rick Anthony (vocals and guitar), Iain Stewart (drums) and Greg Sinclair (guitars). They are often generally described as indie rock but are known to utilize a variety of genres and styles. The band's debut album \"Checkmate Savage\" was released in January 2009 and the follow up \"The Wants\" in October 2010. In June 2014, the band released their third record, \"Strange Friend\".", "title": "" } ]
4178	Is it sensible to keep savings in a foreign currency?	[ { "docid": "393823", "text": "Given that we live in a world rife with geopolitical risks such as Brexit and potential EU breakup, would you say it's advisable to keep some of cash savings in a foreign currency? Probably not. Primarily because you don't know what will happen in the fallout of these sorts of political shifts. You don't know what will happen to banking treaties between the various countries involved. If you can manage to place funds on deposit in a foreign bank/country in a currency other than your home currency and maintain the deposit insurance in that country and not spend too much exchanging your currency then there probably isn't a downside other than liquidity loss. If you're thinking I'll just wire some whatever currency to some bank in some foreign country in which you have no residency or citizenship consideration without considering deposit insurance just so you might protect some of your money from a possible future event I think you should stay away.", "title": "" }, { "docid": "191668", "text": "Is it sensible to keep savings in a foreign currency? The answer varies from one country to the next, but in the UK (or any other mature economy), I would advise against it. There are better ways to hedge against currency risks with the funds readily available to you through your ISA. You can keep your money relatively safe and liquid without ever paying a currency exchange fee.", "title": "" }, { "docid": "450860", "text": "I don't think that it's a good idea to have cash savings in different currencies, unless you know which will be the direction of the wind for that currency. You can suffer a lot of volatility and losses if you just convert your savings to another currency without knowing anything about which direction that pair will take. Today we can see Brexit, but this is a fact that has been discounted by the market, so the currencies are already adjusted to that fact, but we don't know what will happen in the future, maybe Trump will collapse the US economy, or some other economies in Asia will raise to gain more leadership. If you want to invest in an economy, I think that it's a best idea to invest on companies that are working in that country. This is a way of moving your money to other currencies, and at least you can see how is the company performing.", "title": "" }, { "docid": "35511", "text": "would you say it's advisable to keep some of cash savings in a foreign currency? This is primarily opinion based. Given that we live in a world rife with geopolitical risks such as Brexit and potential EU breakup There is no way to predict what will happen in such large events. For example if one keeps funds outside on UK in say Germany in Euro's. The UK may bring in a regulation and clamp down all funds held outside of UK as belonging to Government or tax these at 90% or anything absurd that negates the purpose of keeping funds outside. There are example of developing / under developed economics putting absurd capital controls. Whether UK will do or not is a speculation. If you are going to spend your live in a country, it is best to invest in country. As normal diversification, you can look at keep a small amount invested outside of country.", "title": "" } ]	[ { "docid": "435940", "text": "You have to balance several concerns here. The primary problem is that if you go to the effort of saving your money you want to also be sure that your savings will not lose too much of its value to inflation. Ukraine had a terrible inflation spike in 2015 for obvious reasons. Even as inflation has settled down in 2016, it is stabilizing around 12% which is very high Exchange rates are your next concern. If you lose a large percentage of the value of your money just in the process of exchanging it, that also eats away at the value of your money. If you accept the US Federal Reserve target of 2% inflation, then you should only exchange money that you will hold long enough that both exchange fees will outweigh the 10% inflation advantage. Even in cases where you have placed your money in a foreign currency, there's a chance that your government could freeze accounts denominated in foreign currencies, so there's always the political risk that you have to factor in. For that reason keeping foreign currency in cash also has some appeal because it cannot be confiscated as easily. You could still certainly be robbed, so keeping all of your savings in cash isn't a great solution either. All in all, you are diversifying your savings if you use the strategy of balancing all three methods. Splitting it evenly to 5% for each method isn't the most important. I would suggest taking advantage of good exchange rates (as they appear) to time when you buy foreign currency.", "title": "" }, { "docid": "466950", "text": "\"Having savings only in your home currency is relatively 'low risk' compared with other types of 'low diversification'. This is because, in a simple case, your future cash outflows will be in your home currency, so if the GBP fluctuates in value, it will (theoretically) still buy you the same goods at home. In this way, keeping your savings in the same currency as your future expenditures creates a natural hedge against currency fluctuation. This gets complicated for goods imported from other countries, where base price fluctuates based on a foreign currency, or for situations where you expect to incur significant foreign currency expenditures (retirement elsewhere, etc.). In such cases, you no longer have certainty that your future expenditures will be based on the GBP, and saving money in other currencies may make more sense. In many circumstances, 'diversification' of the currency of your savings may actually increase your risk, not decrease it. Be sure you are doing this for a specific reason, with a specific strategy, and not just to generally 'spread your money around'. Even in case of a Brexit, consider: what would you do with a bank account full of USD? If the answer is \"\"Convert it back to GBP when needed (in 6 months, 5 years, 30, etc.), to buy British goods\"\", then I wouldn't call this a way to reduce your risk. Instead, I would call it a type of investment, with its own set of risks associated.\"", "title": "" }, { "docid": "21055", "text": "\"> We've been deficit spending for generations and we're trillions in the hole, and that's the psychological issue hanging over our heads. Let's unpack that a bit. What does \"\"trillions in the hole\"\" actually mean for the issuer of the dollar? It means that the issuer at various points has to redeem its own interest-bearing dollars (treasuries) for its own non-interest bearing dollars (reserves/notes/coins). That's not a hole. That's moving a balance from the savings account to the checking account at the same bank. You don't think of your savings account balance as the bank being \"\"in the hole\"\" for checking account balances. You implicitly understand that the bank simply marks down the number in one account and marks up the number in the other and you don't fret that the bank might \"\"run out\"\" of checking account balances. Treasuries have this same relationship to reserves. Not similar, not analogous to but the same. Treasury securities are literally interest-bearing accounts at the federal reserve. Reserves are literally demand accounts at the federal reserve. When a treasury matures, a treasury securities account is marked down, a reserve account is marked up. When a treasury is issued, a treasury securities account is marked up and a reserve account is marked down. What you're thinking of as trillions \"\"in the hole\"\" is just trillions in a savings account balance. That's what it means to have \"\"debt\"\" in a currency that you are the issuer of and why foreign-denominated debt is fundamentally different. >so we can design a system that will keep inflation low while we dump money into the economy We already have that. There's no inflation monster under the bed. If there's an inflation problem it's that we're so paranoid about it we're not putting enough money into the economy and so inflicting unnecessary misery on ourselves. > the issue in my mind with dumping money while the debt situation is such a concern, is that speculators could sht the bed and devalue our currency There's nothing a speculator can do vs a sovereign currency that the issuing central bank can't offset. So if you are a sovereign and the issuing central bank is within and beneath your authority, you have the last word and there's no such thing as bond vigilantes. In contrast, if you take on sovereign obligations denominated in currencies where the issuing central bank sits outside your authority as is the case when you borrow/peg to foreign currency or enter a monetary union like the euro, you become just another currency user. Here, your government actually is kinda like a household and can go broke in that foreign currency. Consider how that perspective sheds light on the \"\"mystery\"\" of why some countries actually experience a debt crisis and others don't. Why contrary to all the scaremongering, someplace like Japan for example can have 200% debt:GDP and* near zero interest rates and no sovereign debt crisis. It's because Japan issues the yen, sets the interest rate on the yen and can't run out of yen. People who don't understand this are what gave the [widowmaker](http://www.businessinsider.com/hedge-funds-feeling-confident-about-the-widowmaker-trade-in-japan-2012-12) its name. :) Time after time they line up to place bets on japanese government bond crisis, they're always wrong and always will be.\"", "title": "" }, { "docid": "334495", "text": "You have two problems, money exchange commissions and currency risk. Commissions are always exorbitant. First you must find the cheapest way to get your money converted to the foreign currency and into your brokerage account. The absolute cheapest way may involve some research and financial institution maneuvering. Also I'd forget about anything other than USD for the foreseeable future. Any other foreign currency will probably have higher commissions and a weaker market. Once you have that down, you must avoid needlessly exchanging currencies. Keep a balance in the foreign currency, keep all dividends and capital gains there, and only take local money out of your brokerage account right before using it. That means of course that you need to keep enough local currency to pay taxes on any gains, etc. As for currency risk, there are two solutions. One solution is to buy your risk away using forex. You sell an amount of USD/AED lots that is mostly equivalent to your current investments and then just make sure you don't get margin calls. I'm not sure just how cheap your rates would be in the UAE, but, on average, your investments should still have positive returns. The other solution is to just stop seeing exchange rate fluctuations as losses. If you had USD 100k and now you have USD 115k how are you losing money? Exchange rates can go the other way just fine, you know, and holding USD is a good way to hedge against your country going south.", "title": "" }, { "docid": "260889", "text": "As NRI/PIO (Non-Resident Indian/Person of Indian Origin), the overseas income and transfers in foreign currency are exempt from Indian income taxes. However, the account in India has to be designated NRE or FCNR. There are three kind of accounts that an NRI can maintain Interest earned in NRE and FCNR accounts is exempt from income taxes. Interest earned in NRO accounts is not exempt from income taxes, in fact banks would withhold about 30% of interest (TDS). The exact tax liability would depend upon income generated in India and TDS could be applied towards that liability when the tax returns are filed. There are other implications also of designating the account as NRE or NRO. NRE accounts can only be funded via inward remittance of permitted foreign currency e.g. deposit USD/GBP. So proceeds like rental income, pension etc. that are generated in INR within India can't be deposited in this account. The money deposited in NRE account can grow tax free and can be converted back in any foreign currency freely. On the other hand NRO accounts can be funded through both inward remittance of permitted foreign currency or local income e.g. rental, pension etc. All the amount in this account is treated as Indian originated INR (even if remitted in foreign currency) and thus is taxed as any other bank account. The amount in this account is subject to the annual cap of convertibility of USD 1 million. Both NRE and NRO accounts are maintained in INR and can be Saving and Term Deposit. Any remittance made to these accounts in any foreign currency is converted to INR at the time of deposit and is maintained in INR. FCNR account are held in foreign currency and can only be Term Deposit. Official definitions: Accounts for Non Resident Indians (NRIs) and Persons of Indian Origin (PIOs)", "title": "" }, { "docid": "475478", "text": "\"You might convert all your money in local currency but you need take care of following tips while studying abroad.Here are some money tips that can be useful during a trip abroad. Know about fees :- When you use a debit card or credit card in a foreign country, there are generally two types of transaction fees that may apply: Understand exchange rates :- The exchange rate lets you know the amount of nearby money you can get for each U.S. dollar, missing any expenses. There are \"\"sell\"\" rates for individuals who are trading U.S. dollars for foreign currency, and, the other way around, \"\"purchase\"\" rates. It's a smart thought to recognize what the neighborhood money is worth in dollars so you can comprehend the estimation of your buys abroad. Sites like X-Rates offer a currency converter that gives the current exchange rate, so you can make speedy comparisons. You can utilize it to get a feel for how much certain amount (say $1, $10, $25, $50, $100) are worth in local currency. Remember that rates fluctuate, so you will be unable to suspect precisely the amount of a buy made in a foreign currency will cost you in U.S. dollars. To get cash, check for buddy banks abroad:- If you already have an account with a large bank or credit union in the U.S., you may have an advantage. Being a client of a big financial institution with a large ATM system may make it easier to find a subsidiary cash machine and stay away from an out-of-system charge. Bank of America, for example, is a part of the Global ATM Alliance, which lets clients of taking an interest banks use their debit cards to withdraw money at any Alliance ATM without paying the machine's operator an access fee, in spite of the fact that you may at present be charged for converting dollars into local currency used for purchases. Citibank is another well known bank for travelers because it has 45,000 ATMs in more than 30 countries, including popular study-abroad destinations such as the U.K., Italy and Spain. ATMs in a foreign country may allow withdrawals just from a financial records, and not from savings so make sure to keep an adequate checking balance. Also, ATM withdrawal limits will apply just as they do in the U.S., but the amount may vary based on the local currency and exchange rates. Weigh the benefits of other banks :- For general needs, online banks and even foreign banks can also be good options. With online banks, you don’t have to visit physical branches, and these institutions typically have lower fees. Use our checking account tool to find one that’s a good fit. Foreign banks:- Many American debit cards may not work in Europe, Asia and Latin America, especially those that don’t have an EMV chip that help prevent fraud. Or some cards may work at one ATM, but not another. One option for students who expect a more extended stay in a foreign country is to open a new account at a local bank. This will let you have better access to ATMs, and to make purchases more easily and without as many fees. See our chart below for the names of the largest banks in several countries. Guard against fraud and identity theft:- One of the most important things you can do as you plan your trip is to let your bank know that you’ll be abroad. Include exact countries and dates, when possible, to avoid having your card flagged for fraud. Unfortunately, incidents may still arise despite providing ample warning to your bank. Bring a backup credit card or debit card so you can still access some sort of money in case one is canceled. Passports are also critical — not just for traveling from place to place, but also as identification to open a bank account and for everyday purposes. You’ll want to make two photocopies and give one to a friend or family member to keep at home and put the other in a separate, secure location, just in case your actual passport is lost or stolen.\"", "title": "" }, { "docid": "450184", "text": "\"Depends. The short answer is yes; HSBC, for instance, based in New York, is listed on both the LSE and NYSE. Toyota's listed on the TSE and NYSE. There are many ways to do this; both of the above examples are the result of a corporation owning a subsidiary in a foreign country by the same name (a holding company), which sells its own stock on the local market. The home corporation owns the majority holdings of the subsidiary, and issues its own stock on its \"\"home country's\"\" exchange. It is also possible for the same company to list shares of the same \"\"pool\"\" of stock on two different exchanges (the foreign exchange usually lists the stock in the corporation's home currency and the share prices are near-identical), or for a company to sell different portions of itself on different exchanges. However, these are much rarer; for tax liability and other cost purposes it's usually easier to keep American monies in America and Japanese monies in Japan by setting up two \"\"copies\"\" of yourself with one owning the other, and move money around between companies as necessary. Shares of one issue of one company's stock, on one exchange, are the same price regardless of where in the world you place a buy order from. However, that doesn't necessarily mean you'll pay the same actual value of currency for the stock. First off, you buy the stock in the listed currency, which means buying dollars (or Yen or Euros or GBP) with both a fluctuating exchange rate between currencies and a broker's fee (one of those cost savings that make it a good idea to charter subsidiaries; could you imagine millions a day in car sales moving from American dealers to Toyota of Japan, converted from USD to Yen, with a FOREX commission to be paid?). Second, you'll pay the stock broker a commission, and he may charge different rates for different exchanges that are cheaper or more costly for him to do business in (he might need a trader on the floor at each exchange or contract with a foreign broker for a cut of the commission).\"", "title": "" }, { "docid": "504612", "text": "You can apply for Foreign currency accounts. But they aren't saving accounts by any means, but more like current accounts. Taking money out will involve charges. You have to visit the bank website to figure out what all operations can be performed on your account. Barclays and HSBC allow accounts in foreign currency. Other banks also will be providing the same services. Are there banks where you can open a bank account without being a citizen of that country without having to visit the bank in person Depends on country by country. Are there any online services for investing money that aren't tied to any particular country? Get yourself a trading account and invest in foreign markets i.e. equities, bonds etc. But all in all be ready for the foreign exchange risks involved in denominating assets in multiple currencies.", "title": "" }, { "docid": "554522", "text": "I'll add this to what the other answers said: if you are a renter now, and the real estate you want to buy is a house to live in, then it may be worth it - in a currency devaluation, rent may increase faster than your income. If you pay cash for the home, you also have the added benefit of considerably reducing your monthly housing costs. This makes you more resilient to whatever the future may throw at you - a lower paying job, for instance, or high inflation that eats away at the value of your income. If you get a mortgage, then make sure to get a fixed interest rate. In this case, it protects you somewhat from high inflation because your mortgage payment stays the same, while what you would have had to pay in rent keeps going up an up. In both cases there is also taxes and insurance, of course. And those would go up with inflation. Finally, do make sure to purchase sensibly. A good rule of thumb on how much you can afford to pay for a home is 2.5x - 3.5x your annual income. I do realize that there are some areas where it's common for people to buy homes at a far greater multiple, but that doesn't mean it's a sensible thing to do. Also: I'll second what @sheegaon said; if you're really worried about the euro collapsing, it might give you some peace of mind to move some money into UK Gilts or US Treasuries. Just keep in mind that currencies do move against each other, so you'd see the euro value of those investments fluctuate all the time.", "title": "" }, { "docid": "250790", "text": "\"> but the buying power of that money can be significantly reduced to the point where it's fundamentally useless, i.e. inter-war Germany and many countries in South and Central America. That's true, but how does that come about? The effect on buying power stems from the level of spending in the present period. Too little leaves you anywhere from outright deflation and contraction to weaker growth falling short of capacity. Too much reaches capacity and keeps spending, bidding up prices and driving down purchasing power. It has nothing to do with debt:GDP or interest payments. > Germany managed to skate by by creating a new Deutschmark in a confidence trick, and it worked because Germany is a solid, iron clad manufacturing powerhouse of a lot of stuff. There are two important differences between inter-war Germany and the US. First is that inter-war Germany lost a war. This real shock is kind of important. When you're talking about buying power of money, one side of it is the amount of money in circulation but the other side of it is how much real output there is to buy and German real output capacity collapsed after the war. Their most productive regions were occupied territory and they were no longer a powerhouse manufacturing a lot of stuff, driving down the value of their currency. So lesson number one from Germany: real output collapse harms your currency. The second problem is that losing a war left Germany saddled with war reparations denominated in foreign currency. When you're on the hook for something you don't print you're in a situation where you can run out of money and that's exactly what happened to them. They tried printing more of their own currency to buy the foreign stuff with but that quickly drove down the value of German currency. So lesson number two from Germany is you don't want to be on the hook for a currency you don't issue. Put the two together and you have a real supply shock + foreign-denominated debt eviscerating the buying power of German currency. It wasn't debt:GDP but the real basis for their economy collapsing out from under them pushed along by a need for foreign currency. >My question is, at what point do we engage Washington's unlimited money printing presses until we reach that point? In answer to your question, the printing presses are what funds the real economy. The worry in terms of avoiding \"\"that point\"\" is in making sure we keep that real economy productive and fully funded. Ironically, taking our eye off the ball to focus on budget balance at the expense of real output pushes the economy in the direction you're afraid of going. See also: the euro zone today.\"", "title": "" }, { "docid": "93518", "text": "\"It may seem weird but interest rates are set by a market. Risk is a very large component of the price that a saver will accept to deposit their money in a bank but not the only one. Essentially you are \"\"lending\"\" deposited cash to the bank that you put it in and they will lend it out at a certain risk to themselves and a certain risk to you. By diversifying who they lend to (corporations, home-buyers each other etc.) the banks mitigate a lot of the risk but lending to the bank is still a risky endeavour for the \"\"saver\"\" and the saver accepts a given interest rate for the amount of risk there is in having the money in that particular bank. The bank is also unable to diversify away all possible risk, but tries to do the best job it can. If a bank is seen to take bigger risks and therefore be in greater risk of failing (having a run on deposits) it must have a requisitely higher interest rates on deposits compared to a lower risk bank. \"\"Savers\"\" therefore \"\"shop around\"\" for the best interest rate for a given level of risk which sets the viable interest rate for that bank; any higher and the bank would not make a profit on the money that it lends out and so would not be viable as a business, any lower and savers would not deposit their money as the risk would be too high for the reward. Hence competition (or lack of it) will set the rate as a trade off between risk and return. Note that governments are also customers of the banking industry when they are issuing fixed income securities (bonds) and a good deal of the lending done by any bank is to various governments so the price that they borrow money at is a key determinant of what interest rate the bank can afford to give and are part of the competitive banking industry whether they want to be or not. Since governments in most (westernised) countries provide insurance for deposits the basic level of (perceived) risk for all of the banks in any given country is about the same. That these banks lend to each other on an incredibly regular basis (look into the overnight or repo money market if you want to see exactly how much, the rates that these banks pay to and receive from each other are governed by interbank lending rates called Libor and Euribor and are even more complicated than this answer) simply compounds this effect because it makes all of the banks reliant on each other and therefore they help each other to stay liquid (to some extent). Note that I haven't mentioned currency at all so far but this market in every country applies over a number of currencies. The way that this occurs is due to arbitrage; if I can put foreign money into a bank in a country at a rate that is higher than the rate in its native country after exchange costs and exchange rate risk I will convert all of my money to that currency and take the higher interest rate. For an ordinary individual's savings that is not really possible but remember that the large multinational banks can do exactly the same thing with billions of dollars of deposits and effectively get free money. This means that either the bank's interest rate will fall to a risk adjusted level or the exchange rate will move. Either of those moves will remove the potential for making money for nothing. In this case, therefore it is both the exchange rate risk (and costs) as well as the loan market in that country that set the interest rate in foreign currencies. Demand for loans in the foreign currency is not a major mover for the same reason. Companies importing from foreign entities need cash in foreign currencies to pay their bills and so will borrow money in other currencies to fulfil these operations which could come from deposits in the foreign currency if they were available at a lower interest rate than a loan in local currency plus the costs of exchange but the banks will be unwilling to loan to them for less than the highest return that they can get so will push up interest rates to their risk level in the same way that they did in the market before currencies were taken into account. Freedom of movement of foreign currencies, however, does move interest rates in foreign currencies as the banks want to be able to lend as much of currencies that are not freely deliverable as they can so will pay a premium for these currencies. Other political moves such as the government wanting to borrow large amounts of foreign currency etc. will also move the interest rate given for foreign currencies not just because loaning to the government is less risky but also because they sometimes pay a premium (in interest) for being able to borrow foreign currency which may balance this out. Speculation that a country may change its base interest rate will move short term rates, and can move long term rates if it is seen to be a part of a country's economic strategy. The theory behind this is deep and involved but the tl;dr answer would be the standard \"\"invisible hand\"\" response when anything market or arbitrage related is involved. references: I work in credit risk and got a colleague who is also a credit risk consultant and economist to look over it. Arbitrage theory and the repo markets are both fascinating so worth reading about!\"", "title": "" }, { "docid": "217727", "text": "\"The simplest, most convenient way I know of to \"\"move your savings to Canada\"\" is to purchase an exchange-traded fund like FXC, the CurrencyShares Canadian Dollar Trust, or a similar instrument. (I identify this fund because I know it exists, not because I particularly recommend it.) Your money will be in Canadian currency earning Canadian interest rates. You will pay a small portion of that interest in fees. Since US banks are already guaranteed by the FDIC up to $250,000 per account, I don't really think you avoid any risks associated with the failure of an individual bank, but you might fare better if the US currency is subject to inflation or unfavorable foreign-exchange movements - not that such a thing would be a direct risk of a bank failure, but it could happen as a result of actions taken by the Federal Reserve under the auspices of aiding the economy if the economy worsens in the wake of a financial crisis - or, for that matter, if it worsens as a result of something else, including legislative, regulatory, or executive policies. Read the prospectus to understand additional risks with this investment. One of them is foreign-exchange risk. If the US economy and currency strengthen relative to the Canadian economy and its currency, you may lose substantial amounts of purchasing power. Additionally, one of the possible results of a financial crisis is a \"\"flight to safety\"\"; the global financial markets still seem to think the US dollar is pretty safe, and they may bid it up as they have done in the past, resulting in losses to your position (at least in the short term). I do not personally recommend moving all your savings to Canada, especially if it deprives you of income from more profitable investments over the long term, but moving some of your savings to Canada at least isn't a stupid idea, and it may turn out to be somewhat profitable. Having some Canadian currency is also a good idea if you plan to spend the money that you are saving on Canadian goods in the intermediate future.\"", "title": "" }, { "docid": "468462", "text": "Your bank will gladly help you convert your Indian savings accounts into NRO savings accounts. You cannot change these accounts into NRE accounts directly; NRE accounts are supposed to be funded via deposits made from foreign currency accounts. Under the liberalized schemes available now, you can transfer the money in your regular savings account into your account abroad, converting it into foreign currency, if you (and your CA) provide proof to your bank (and the Reserve Bank of India) that you have paid all applicable taxes on the money in your savings account. And then you can transfer it all back into your NRE account. Perhaps you can combine these two steps into a single one, thereby putting the money in your regular savings account into an NRE account in one step, but I am sure that there will be lots of fees involved (e.g. you might get whacked by commissions, as well as the exchange rate differential as if you converted Indian rupees to US dollars, say, and then converted the dollars back to rupees) just as if you did the two-step conversion. There are no taxes involved in moving your own money into different accounts but there can be lots of fees and service charges.", "title": "" }, { "docid": "166412", "text": "\"Quantitative Easing Explained: http://www.npr.org/blogs/money/2010/10/07/130408926/quantitative-easing-explained The short of it is that you're right; the Fed (or another country's Central Bank) is basically creating a large amount of new money, which it then injects into the economy by buying government and institutional debt. This is, in fact, one of the main jobs of the central bank for a currency; to manage the money supply, which in most fiat systems involves slowly increasing the amount of money to keep the economy growing (if there isn't enough money moving around in the economy it's reflected in a slowdown in GDP growth), while controlling inflation (the devaluation of a unit of currency with respect to most or all things that unit will buy including other currencies). Inflation's primary cause is defined quite simply as \"\"too many dollars chasing too few goods\"\". When demand is low for cash (because you have a lot of it) while demand for goods is high, the suppliers of those goods will increase their price for the goods (because people are willing to pay that higher price) and will also produce more. With quantitative easing, the central bank is increasing the money supply by several percentage points of GDP, much higher than is normally needed. This normally would cause the two things you mentioned: Inflation - inflation's primary cause is \"\"too many dollars chasing too few goods\"\"; when money is easy to get and various types of goods and services are not, people \"\"bid up\"\" the price on these things to get them (this usually happens when sellers see high demand for a product and increase the price to take advantage and to prevent a shortage). This often happens across the board in a situation like this, but there are certain key drivers that can cause other prices to increase (things like the price of oil, which affects transportation costs and thus the price to have anything shipped anywhere, whether it be the raw materials you need or the finished product you're selling). With the injection of so much money into the economy, rampant inflation would normally be the result. However, there are other variables at play in this particular situation. Chief among them is that no matter how much cash is in the economy, most of it is being sat on, in the form of cash or other \"\"safe havens\"\" like durable commodities (gold) and T-debt. So, most of the money the Fed is injecting into the economy is not chasing goods; it's repaying debt, replenishing savings and generally being hoarded by consumers and institutions as a hedge against the poor economy. In addition, despite how many dollars are in the economy right now, those dollars are in high demand all around the world to buy Treasury debt (one of the biggest safe havens in the global market right now, so much so that buying T-debt is considered \"\"saving\"\"). This is why the yields on Treasury bonds and notes are at historic lows; it's bad everywhere, and U.S. Government debt is one of the surest things in the world market, especially now that Euro-bonds have become suspect. Currency Devaluation - This is basically specialized inflation; when there are more dollars in the market than people want to have in order to use to buy our goods and services, demand for our currency (the medium of trade for our goods and services) drops, and it takes fewer Euros, Yen or Yuan to buy a dollar. This can happen even if demand for our dollars inside our own borders is high, and is generally a function of our trade situation; if we're buying more from other countries than they are from us, then our dollars are flooding the currency exchange markets and thus become cheaper because they're easy to get. Again, there are other variables at play here that keep our currency strong. First off, again, it's bad everywhere; nobody's buying anything from anyone (relatively speaking) and so the relative trade deficits aren't moving much. In addition, devaluation without inflation is self-stablizing; if currency devalues but inflation is low, the cheaper currency makes the things that currency can buy cheaper, which encourages people to buy them. At the same time, the more expensive foreign currency increases the cost in dollars of foreign-made goods. All of this can be beneficial from a money policy standpoint; devaluation makes American goods cheaper to Americans and to foreign consumers alike than foreign goods, and so a policy that puts downward pressure on the dollar but doesn't make inflation a risk can help American manufacturing and other producer businesses. China knows this just as well as we do, and for decades has been artificially fixing the exchange rate of the Renmin B (Yuan) lower than its true value against the dollar, meaning that no matter how cheap American goods get on the world market, Chinese goods are still cheaper, because by definition the Yuan has greater purchasing power for the same cost in dollars. In addition, dollars aren't only used to buy American-made goods and services. The U.S. has positioned its currency over the years to be an international medium of trade for several key commodities (like oil), and the primary currency for global lenders like the IMF and the World Bank. That means that dollars become necessary to buy these things, and are received from and must be repaid to these institutions, and thus the dollar has a built-in demand pretty much regardless of our trade deficits. On top of all that, a lot of countries base their own currencies on our dollar, by basically buying dollars (using other valuable media like gold or oil) and then holding that cash in their own central banks as the store of value backing their own paper money. This is called a \"\"dollar board\"\". Their money becomes worth a particular fraction of a dollar by definition, and that relationship is very precisely controllable; with 10 billion dollars in the vault, and 20 billion Kabukis issued from Kabukistan's central bank, a Kabuki is worth $.50. Print an additional 20 billion Kabuki and the value of one Kabuki decreases to $.25; buy an additional 10 billion dollars and the Kabuki's value increases again to $.50. Quite a few countries do this, mostly in South America, again creating a built-in demand for U.S. dollars and also tying the U.S. dollar to the value of the exports of that country. If Kabukistan's goods become highly demanded by Europe, and its currency increases relative to the dollar, then the U.S. dollar gets a boost because by definition it is worth an exact, fixed number of Kabukis (and also because a country with a dollar board typically has no problem accepting dollars as payment and then printing Kabukis to maintain the exchange rate)\"", "title": "" }, { "docid": "263648", "text": "On my recent visit to the bank, I was told that money coming into the NRE account can only be foreign currency and for NRO accounts, the money can come in local currency but has to be a valid source of income (e.g. rent or investments in India). Yes this is correct as per FMEA regulation in India. Now if we use 3rd party remittances like Remitly or Transferwise etc, they usually covert the foreign currency into local currency like INR and then deposit it. The remittance services are better suited for transferring funds to Normal Savings accounts of your loved ones. Most remittance services would transfer funds using a domestic clearing network [NEFT] and hence the trace that funds originated outside of India is lost. There could be some generic remittance that may have direct tie-up with some banks to do direct transfers. How can we achieve this in either NRE/NRO accounts? If not, what are the other options ? You can do a Wire Transfer [SWIFT] from US to Indian NRE account. You can also use the remittance services [if available] from Banks where you hold NRE Account. For example RemittoIndia from HDFC for an NRE account in HDFC, or Money2India from ICICI for an NRE account in ICICI or QuickRemit from SBI etc. These would preserve the history that funds originated from outside India. Similarly you can also deposit a Foreign Currency Check into Indian Bank Account. The funds would take around month or so to get credited. All other funds can be deposited in NRO account.", "title": "" }, { "docid": "157907", "text": "\"Currencies that are pegged or fixed require that foreign currencies are held by the central issuer at a proportional amount. This is analogous to having a portfolio of currencies that the central bank issues shares from - in the form of its own currency. We will continue with this analogy, if the central bank says these \"\"shares\"\" are worth $1, but the underlying components of the portfolio are worth $0.80 and decreasing, then it is expensive for the central bank to maintain its peg, and eventually they will have to disregard the peg as people start questioning the central bank's solvency. (People will know the $1 they hold is not really worth what the central bank says it is, because of the price changes people experience in buying goods and services, especially when it comes to imports. Shadow economies will also trade using a currency more reflective of labor, which happens no matter what the government's punishments are for doing so). Swiss National Bank (central bank) did this in early 2015, as it experienced volatility in the Euro which it had previously been trying to keep it's currency pegged to. It became too expensive for it to keep this peg on its own. The central bank can devalue its currency by adjusting the proportions of the reserve, such as selling a lot of foreign currency X, buying more of currency Y. They can and do take losses doing this. (Swiss National Bank is maintaining a large loss) They can also flood their economy with more of their currency, diluting the value of each individual 1 dollar equivalent. This is done by issuing bonds or monetizing goods and services from the private sector in exchange for bonds. People colloquially call this \"\"printing money\"\" but it is a misnomer in this day and age where printers are not relevant tools. The good and service goes onto the central bank's balance book, and the company/entity that provided the service now has a bond on its book which can be immediately sold to someone else for cash (another reading is that the bond is as good as cash). The bond didn't previously exist until the central bank said it did, and central banks can infinitely exchange goods and services for bonds. Bond monetization (also called Quantitative Easing) is practiced by the Federal Reserve in the United States, Bank of Japan, European Central Bank and now the Central Bank of the Republic of China\"", "title": "" }, { "docid": "283044", "text": "HDFC Bank offers an easy and comfortable way to hold the foreign currency for NRIs with a RFC Savings Account. You can deposit money in 4 different currencies and anytime convert them into money. Apply for an HDFC Bank RFC Account now!", "title": "" }, { "docid": "228459", "text": "If you have significant assets, such as a large deposit, then diversification of risks such as currency risk is good practice - there are many good options, but keeping 100% of it in roubles is definitely not a good idea, nor is keeping 100% of it in a single foreign currency. Of course, it would be much more beneficial to have done it yesterday, and moments of extreme volatility generally are a bad time to make large uninformed trades, but if the deposit is sufficiently large (say, equal to annual expenses) then it would make sense to split it among different currencies and also different types of assets as well (deposit/stocks/precious metals/bonds). The rate of rouble may go up and down, but you also have to keep in mind that future events such as fluctuating oil price may risk a much deeper crisis than now, and you can look to experiences of the 1998 crisis as an example of what may happen if the situation continues to deteriorate.", "title": "" }, { "docid": "185983", "text": "Here's what the GnuCash documentation, 10.5 Tracking Currency Investments (How-To) has to say about bookkeeping for currency exchanges. Essentially, treat all currency conversions in a similar way to investment transactions. In addition to asset accounts to represent holdings in Currency A and Currency B, have an foreign exchange expenses account and a capital gains/losses account (for each currency, I would imagine). Represent each foreign exchange purchase as a three-way split: source currency debit, foreign exchange fee debit, and destination currency credit. Represent each foreign exchange sale as a five-way split: in addition to the receiving currency asset and the exchange fee expense, list the transaction profit in a capital gains account and have two splits against the asset account of the transaction being sold. My problems with this are: I don't know how the profit on a currency sale is calculated (since the amount need not be related to any counterpart currency purchase), and it seems asymmetrical. I'd welcome an answer that clarifies what the GnuCash documentation is trying to say in section 10.5.", "title": "" }, { "docid": "575046", "text": "why should I have any bias in favour of my local economy? The main reason is because your expenses are in the local currency. If you are planning on spending most of your money on foreign travel, that's one thing. But for most of us, the bulk of our expenses are incurred locally. So it makes sense for us to invest in things where the investment return is local. You might argue that you can always exchange foreign results into local currency, and that's true. But then you have two risks. One risk you'll have anywhere: your investments may go down. The other risk with a foreign investment is that the currency may lose value relative to your currency. If that happens, even a good performing investment can go down in terms of what it can return to you. That fund denominated in your currency is really doing these conversions behind the scenes. Unless the bulk of your purchases are from imports and have prices that fluctuate with your currency, you will probably be better off in local investments. As a rough rule of thumb, your country's import percentage is a good estimate of how much you should invest globally. That looks to be about 20% for Australia. So consider something like 50% local stocks, 20% local bonds, 15% foreign stocks, 5% foreign bonds, and 10% local cash. That will insulate you a bit from a weak local currency while not leaving you out to dry with a strong local currency. It's possible that your particular expenses might be more (or less) vulnerable to foreign price fluctuations than the typical. But hopefully this gives you a starting point until you can come up with a way of estimating your personal vulnerability.", "title": "" }, { "docid": "496857", "text": "\"HSBC, Hang Seng, and other HK banks had a series of special savings account offers when I lived in HK a few years ago. Some could be linked to the performance of your favorite stock or country's stock index. Interest rates were higher back then, around 6% one year. What they were effectively doing is taking the interest you would have earned and used it to place a bet on the stock or index in question. Technically, one way this can be done, for instance, is with call options and zero coupon bonds or notes. But there was nothing to strategize with once the account was set up, so the investor did not need to know how it worked behind the scenes... Looking at the deposit plus offering in particular, this one looks a little more dangerous than what I describe. See, now we are in an economy of low almost zero interest rates. So to boost the offered rate the bank is offering you an account where you guarantee the AUD/HKD rate for the bank in exchange for some extra interest. Effectively they sell AUD options (or want to cover their own AUD exposures) and you get some of that as extra interest. Problem is, if the AUD declines, then you lose money because the savings and interest will be converted to AUD at a contractual rate that you are agreeing to now when you take the deposit plus account. This risk of loss is also mentioned in the fine print. I wouldn't recommend this especially if the risks are not clear. If you read the fine print, you may determine you are better off with a multicurrency account, where you can change your HK$ into any currency you like and earn interest in that currency. None of these were \"\"leveraged\"\" forex accounts where you can bet on tiny fluctuations in currencies. Tiny being like 1% or 2% moves. Generally you should beware anything offering 50:1 or more leverage as a way to possibly lose all of your money quickly. Since you mentioned being a US citizen, you should learn about IRS form TD F 90-22.1 (which must be filed yearly if you have over $10,000 in foreign accounts) and google a little about the \"\"foreign account tax compliance act\"\", which shows a shift of the government towards more strict oversight of foreign accounts.\"", "title": "" }, { "docid": "14781", "text": "\"Yes, you're still exposed to currency risk when you purchase the stock on company B's exchange. I'm assuming you're buying the shares on B's stock exchange through an ADR, GDR, or similar instrument. The risk occurs as a result of the process through which the ADR is created. In its simplest form, the process works like this: I'll illustrate this with an example. I've separated the conversion rate into the exchange rate and a generic \"\"ADR conversion rate\"\" which includes all other factors the bank takes into account when deciding how many ADR shares to sell. The fact that the units line up is a nice check to make sure the calculation is logically correct. My example starts with these assumptions: I made up the generic ADR conversion rate; it will remain constant throughout this example. This is the simplified version of the calculation of the ADR share price from the European share price: Let's assume that the euro appreciates against the US dollar, and is now worth 1.4 USD (this is a major appreciation, but it makes a good example): The currency appreciation alone raised the share price of the ADR, even though the price of the share on the European exchange was unchanged. Now let's look at what happens if the euro appreciates further to 1.5 USD/EUR, but the company's share price on the European exchange falls: Even though the euro appreciated, the decline in the share price on the European exchange offset the currency risk in this case, leaving the ADR's share price on the US exchange unchanged. Finally, what happens if the euro experiences a major depreciation and the company's share price decreases significantly in the European market? This is a realistic situation that has occurred several times during the European sovereign debt crisis. Assuming this occurred immediately after the first example, European shareholders in the company experienced a (43.50 - 50) / 50 = -13% return, but American holders of the ADR experienced a (15.95 - 21.5093) / 21.5093 = -25.9% return. The currency shock was the primary cause of this magnified loss. Another point to keep in mind is that the foreign company itself may be exposed to currency risk if it conducts a lot of business in market with different currencies. Ideally the company has hedged against this, but if you invest in a foreign company through an ADR (or a GDR or another similar instrument), you may take on whatever risk the company hasn't hedged in addition to the currency risk that's present in the ADR/GDR conversion process. Here are a few articles that discuss currency risk specifically in the context of ADR's: (1), (2). Nestle, a Swiss company that is traded on US exchanges through an ADR, even addresses this issue in their FAQ for investors. There are other risks associated with instruments like ADR's and cross-listed companies, but normally arbitrageurs will remove these discontinuities quickly. Especially for cross-listed companies, this should keep the prices of highly liquid securities relatively synchronized.\"", "title": "" }, { "docid": "210796", "text": "If your savings are in USD and will be making purchases using USD, then it will no longer go as far as it used to. I assume most Americans currently have their savings accounts in USD, so the value of those accounts will decrease. If you have investments in stocks or foreign currencies, your exposure may be less, but it depends. For example, stocks in companies that hold a lot of USD will also be hit hard, as will be currencies of nations that are still holding a lot of USD if the value of the USD is crashing. If you have a lot of debt measured in USD, while have a lot of assets that have nothing to do with USD, then you might make out like a bandit, since if you assume the value of the USD is falling, then it would become easier to sell off your other assets to pay off the debt.", "title": "" }, { "docid": "69171", "text": "Wire transfers are the best method. Costs can vary from $10 to $100 or more, depending on the banks and countries involved. There's rarely any saving using the same bank, although HSBC may have reduced charges if you have Premier accounts in both countries (for a one-off transaction, it may not be worth the effort to open an account). However, that cost is insignificant compared to your possible losses on the currency exchange. Assuming your money is currently in Hong Kong Dollars (HKD), it will need to be converted to US Dollars (USD). One place where it could be converted is at your Hong Kong bank. You'll get their retail rate. Make sure you are aware of the rate they will use, and any fees, in advance. Expect to pay around 2-3% from the mid-market rate (the rate you see quoted online, which doesn't fluctuate much for HKD-USD as the currencies are linked). Another place where the currency could be converted is at your US bank. You really don't get any control over that if it arrives as HKD and is then automatically converted into your USD. The rate and fees could be quite poor, especially if it is a minor US bank that has to deal with anther bank for foreign currency. For amounts of this size, it's worthwhile using a specialist currency conversion company instead. Currency Fair in Ireland is one. It's a peer-to-peer exchange that is generally the best deal (at least for the currency pairs I use). You wire the money to them, do the exchange on their site at a rate that is much closer to 0.5% from the midrate, then the money is transferred out by wire for a few dollars. Adds a few days to the process, but will possibly save you close to US$1000. Another established option is Currency Online in New Zealand. There are probably also specialist currency exchange companies in Hong Kong. The basic rule is, don't let the banks exchange currencies at rates that suit them, use a third party that offers a better rate and lower fees.", "title": "" }, { "docid": "586772", "text": "Citizens of India who are not residents to India (have NRI status) are not entitled to have ordinary savings accounts in India. If you have such accounts (e.g. left them behind to support your family while you are abroad), they need to be converted to NRO (NonResident Ordinary) accounts as soon as possible. Your bank will have forms for completion of this process. Any interest that these accounts earn will be taxable income to you in India, and possibly in the U.K. too, though tax treaties (or Double Taxation Avoidance Agreements) generally allow you to claim credit for taxes paid to other countries. Now, with regard to your question, NRIs are entitled to make deposits into NRO accounts as well as NRE (NonResident External) accounts. The differences are that money deposited into an NRE account, though converted to Indian Rupees, can be converted back very easily to foreign currency if need be. However, the re-conversion is at the exchange rate then in effect, and you may well lose that 10% interest earned because of a change in exchange rate. Devaluation of the Indian Rupee as occurred several times in the past 70 years. Once upon a time, it was essentially impossible to take money in an NRO account and convert it to foreign currency, but under the new recently introduced schemes, money in an NRO account can also be converted to foreign currencies, but it needs certification by a CA, and various forms to be filled out, and thus is more hassle. interest earned by the money in an NRE account is not taxable income in India, but is taxable income in the U.K. There is no taxable event (neither in U.K. nor in India) when you change an ordinary savings account held in India into an NRO account, or when you deposit money from abroad into an NRE or NRO account in an Indian bank. What is taxable is the interest that you receive from the Indian bank. In the case of an NRO account, what is deposited into your NRO account is the interest earned less the (Indian) income tax (usually 20%) deducted at the source (TDS) and sent to the Income Tax Authority on your behalf. In the case of an NRE account, the full amount of interest earned is deposited into the NRE account -- no TDS whatsoever. It is your responsibility to declare these amounts to the U.K. income tax authority (HM Revenue?) and pay any taxes due. Finally, you say that you recently moved to the U.K. for a job. If this is a temporary job and you might be back in India very soon, all the above might not be applicable to you since you would not be classified as an NRI at all.", "title": "" }, { "docid": "124862", "text": "\"To speak to this a little more broadly: apart from groups like hedge funds and other investors investing for purely speculative purposes, one of the major purposes of forwards (and, for that matter, futures) for companies in the \"\"real economy\"\" is to \"\"lock in\"\" a particular price in advance (or to reduce the risk of some kind of investment or transaction). Investopedia defines a currency forward as follows (with a few key points emphasized): [A currency forward is] a binding contract in the foreign exchange market that locks in the exchange rate for the purchase or sale of a currency on a future date. A currency forward is essentially a hedging tool that does not involve any upfront payment. The other major benefit of a currency forward is that it can be tailored to a particular amount and delivery period, unlike standardized currency futures. This can be a major advantage for planning and risk management purposes. For example, if I know I'm going to have to pay $1 million USD in the future and most of my revenue is in Euros, the actual amount I'll have to pay will vary based on the exchange rate between Euros and dollars. Thus, it's very worthwhile for me to be able to \"\"lock in\"\" a particular exchange rate so that I know exactly how much I'm going to pay relative to my projected revenue. The goal isn't necessarily to make money off the transaction (maybe they do, maybe they don't) as much as to reduce risk and improve planning ability. The fact that it doesn't involve an up-front payment is also a major advantage. It's usually a bad practice to \"\"sit on\"\" cash for a year if you can avoid it. Another key point: savings accounts pay less interest than inflation. If inflation is 3% and your savings account pays 1%, that looks remarkably like a guaranteed 2% loss to me.\"", "title": "" }, { "docid": "569928", "text": "Is the balance (in dollars, say) automatically converted to rupees when I try to: You can't transact on this account like you do on savings account. So there is NO ATM/Debit Card/Net Banking. You have to walk-in to the Branch and withdraw in local currency or in travel cards as required. Am I correct in understanding that a resident foreign currency account cannot have deposits made into it in rupees, say if someone wants to transfer money to me using IMPS? Deposits are restricted. See RBI circular", "title": "" }, { "docid": "308208", "text": "So your accountant certainly knows much more than I do about Israeli tax law and its interactions with US tax law, which is zero. I'm going to look at this problem from the investment perspective which I hope to convince you is the most important place to start. Then you can adjust for interactions between the Isreali and US tax codes. Even if the tax breaks are exceptional, it would be hard to recommend buying real estate as an investment in the 7-10 year time frame. Especially if this real estate is in the US. Open/Closing fees, mortgage fees, risk of property devaluation, bad-renters, acts of god, insurance costs and tax complications make short to medium term investments in real estate a particularly risky way to invest. Buying a local apartment and renting is somewhat more reasonable as you don't have to worry about the currency conversion and you can do a lot more research in your local environment and keep a closer eye on the property, it is still this a pretty concentrated risk. Saving and investing using tax-advantaged accounts is generally considered a great way to build toward a down payment in the medium term. A mixture of mostly local bonds with some local and foreign stocks and more and more cash as it gets close to purchase time is generally what is recommended when saving for a home. This mixture is relatively safe and will tend to grow steadily without the concentrated risk of a real estate investment. PFIC rules are complicated and certainly worth taking some time to understand, but owning real estate especially in a foreign country seems much more complicated and certainly riskier. There may be some rule that makes investing in REITs much better than normal stocks in these particular accounts though I would be surprised if that were the case. It is generally not true for people under just he US tax code. So while option (1) may not be the absolute best from a tax perspective it would certainly be my guess as the most likely to succeed.", "title": "" }, { "docid": "535151", "text": "There's another dimension here as currency conversion isn't necessarily the final answer. As stated by others, converting money between the three should theoretically end up with the exact same value, less transactional costs. However the kink is that the price of most products are not updated as the currencies change. In many cases the price difference is such that even accounting for shipping and exchange fees, purchasing a product from a distributor in a foreign country can be cheaper than just picking it up at the local store. You might even be able to take advantage of this when purchasing at a single store. If that store is set up to accept multiple currencies then it's a matter of looking at the conversion rates the moment you are buying and deciding which one is the cheapest route for you. Of course, this generally will not work for smaller purchases like a cup of coffee or a meal. Primarily because the fee for the exchange might eclipse any savings.", "title": "" }, { "docid": "95044", "text": "The ruble was, is and will be very unstable because of unstable political situation in Russia and the economy strongly dependent of the export of raw resources. What you can do? I assume, you want to minimize risk. The best way to achieve that is to make your savings in some stable currency. Euro and Swiss Franc are currently very stable currencies, so storing your surpluses in them is a very good option if you want to keep your money safe. To prevent political risk, you should keep your money in countries with stable political regime, which are unlikely to 'nationalize' the savings of the citizens in predictable future. As for your existing savings in rubles, it's a hard deal. I assume, as the web developer, you have a plenty of money, which have lost a lot of value. If you convert them to euro or francs, you will preserver the current value (after the loss). You'll safe them agaist ruble falling down, but in case the ruble will return to previous value, you'll loose. Keeping savings in instable currencies is, however, speculation, like investing in gold etc. So if you can mentally accept the loss and want to sleep good, convert them. You have also option to invest in properties, for example buy an extra appartment. It's a good way to deal with financial surplus in Europe in US, however you should be aware, in Russland it's connected with the political risk. The real estates can be confiscated in any moment by the state and you can't run away with it (the savings can also be confiscated, but there's a fair chance you'll manage to rescue them if you act quickly).", "title": "" } ]
640	Inside the body, falciparum parasites reproduce asexually.	[ { "docid": "6503185", "text": "Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.", "title": "Malaria biology and disease pathogenesis: insights for new treatments" } ]	[ { "docid": "8373753", "text": "The seasonal dynamics and spatial distributions of Anopheles mosquitoes and Plasmodium falciparum parasites were studied for one year at 30 villages in Malindi, Kilifi, and Kwale Districts along the coast of Kenya. Anopheline mosquitoes were sampled inside houses at each site once every two months and malaria parasite prevalence in local school children was determined at the end of the entomologic survey. A total of 5,476 Anopheles gambiae s.l. and 3,461 An. funestus were collected. Species in the An. gambiae complex, identified by a polymerase chain reaction, included 81.9% An. gambiae s.s., 12.8% An. arabiensis, and 5.3% An. merus. Anopheles gambiae s.s. contributed most to the transmission of P. falciparum along the coast as a whole, while An. funestus accounted for more than 50% of all transmission in Kwale District. Large spatial heterogeneity of transmission intensity (< 1 up to 120 infective bites per person per year) resulted in correspondingly large and significantly related variations in parasite prevalence (range = 38-83%). Thirty-two percent of the sites (7 of 22 sites) with malaria prevalences ranging from 38% to 70% had annual entomologic inoculation rates (EIR) less than five infective bites per person per year. Anopheles gambiae s.l. and An. funestus densities in Kwale were not significantly influenced by rainfall. However, both were positively correlated with rainfall one and three months previously in Malindi and Kilifi Districts, respectively. These unexpected variations in the relationship between mosquito populations and rainfall suggest environmental heterogeneity in the predominant aquatic habitats in each district. One important conclusion is that the highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys. The field-based estimate of entomologic parameters on a district level does not provide a sensitive indicator of transmission intensity in this study.", "title": "Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast." }, { "docid": "25499612", "text": "Despite its key role in determining the stability and intensity of malaria transmission, the infectiousness of human populations to mosquitoes has rarely been estimated. Field-based analyses of malaria transmission have frequently relied on the prevalence of asexual parasites or gametocytes as proxies for infectiousness. We now summarize empirical data on human infectiousness from Africa and Papua New Guinea. Over a wide range of transmission intensities there is little relationship between the infectiousness of human populations to vector mosquitoes and mosquito-to-human transmission intensity. We compare these data with the predictions of a stochastic simulation model of Plasmodium falciparum epidemiology. This model predicted little variation in the infectiousness of the human population for entomologic inoculation rates (EIRs) greater than approximately 10 infectious bites per year, demonstrating that the lack of relationship between the EIR and the infectious reservoir can be explained without invoking any effects of acquired transmission-blocking immunity. The near absence of field data from areas with an EIR < 10 per year precluded validation of the model predictions for low EIR values. These results suggest that interventions reducing mosquito-to-human transmission will have little or no effect on human infectiousness at the levels of transmission found in most rural areas of sub-Saharan Africa. Unless very large reductions in transmission can be achieved, measures to prevent mosquito-to-human transmission need to be complemented with interventions that reduce the density or infectiousness of blood stage parasites.", "title": "Infectiousness of malaria-endemic human populations to vectors." }, { "docid": "2460304", "text": "Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.", "title": "Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance." }, { "docid": "40900567", "text": "The multiplication rates and invasiveness of Plasmodium falciparum parasites isolated from adult Thai patients hospitalized with uncomplicated malaria (n=34) were compared with those from persons with severe malaria (n=42). To simulate severe malaria and control for host effects, the in vitro cultures were adjusted to 1% parasitemia and used the same red blood cell donor. P. falciparum isolates from persons with severe malaria had initial cycle multiplication rates in vitro that were 3-fold higher than those from uncomplicated malaria (median [95% confidence interval], 8.3 [7. 1-10.5] vs. 2.8 [1.7-3.9]; P=.001). Parasites causing severe malaria exhibited unrestricted red blood cell invasion, whereas those from uncomplicated malaria were restricted to a geometric mean of 40 (31%-53%) of red blood cells. P. falciparum parasites causing severe malaria were less selective and multiplied more at high parasitemias than those causing uncomplicated malaria.", "title": "Parasite multiplication potential and the severity of Falciparum malaria." }, { "docid": "21392703", "text": "All organisms must trade off resource allocation between different life processes that determine their survival and reproduction. Malaria parasites replicate asexually in the host but must produce sexual stages to transmit between hosts. Because different specialized stages are required for these functions, the division of resources between these life-history components is a key problem for natural selection to solve. Despite the medical and economic importance of these parasites, their reproductive strategies remain poorly understood and often seem counterintuitive. Here, we tested recent theory predicting that in-host competition shapes how parasites trade off investment in in-host replication relative to between-host transmission. We demonstrate, across several genotypes, that Plasmodium chabaudi parasites detect the presence of competing genotypes and facultatively respond by reducing their investment in sexual stages in the manner predicted to maximize their competitive ability. Furthermore, we show that genotypes adjust their allocation to sexual stages in line with the availability of exploitable red blood cell resources. Our findings are predicted by evolutionary theory developed to explain life-history trade-offs in more traditionally studied multicellular taxa and suggest that the answer to the long-standing question of why so few transmission stages are produced is that in most natural infections heavy investment in reproduction may compromise in-host survival.", "title": "Competition and the evolution of reproductive restraint in malaria parasites." }, { "docid": "4336849", "text": "CHLOROQUINE is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function14. Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles5. The discovery that verapamil partially reverses chloroquine resistance in vitro 6 led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant (mdr) tumor cell lines. Indeed, Plasmodium falciparum contains at least two mdr-like genes7,8, one of which has been suggested to confer the chloroquine resistant (CQR) phenotype7,9,10. To determine if either of these genes is linked to chloroquine resistance, we performed a genetic cross between CQR and chloroquine-susceptible (CQS) clones of P. falciparum. Examination of 16 independent recombinant progeny indicated that the rapid efflux phenotype is controlled by a single gene or a closely linked group of genes. But, there was no linkage between the rapid efflux, CQR phenotype and either of the mdr-like P. falciparum genes or amplification of those genes. These data indicate that the genetic locus governing chloroquine efflux and resistance is independent of the known mdr-like genes.", "title": "Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross" }, { "docid": "18074797", "text": "BACKGROUND Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR approximately 43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR approximately 586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. CONCLUSIONS Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required.", "title": "Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies" }, { "docid": "12409683", "text": "BACKGROUND Artemisinin combination therapies (ACT), which are increasingly being introduced for treatment of Plasmodium falciparum malaria, are more effective against sexual stage parasites (gametocytes) than previous first-line antimalarials and therefore have the potential to reduce parasite transmission. The size of this effect is estimated in symptomatic P. falciparum infections. METHODS Data on 3,174 patients were pooled from six antimalarial trials conducted in The Gambia and Kenya. Multivariable regression was used to investigate the role of ACT versus non-artemisinin antimalarial treatment, treatment failure, presence of pre-treatment gametocytes and submicroscopic gametocytaemia on transmission to mosquitoes and the area under the curve (AUC) of gametocyte density during the 28 days of follow up. RESULTS ACT treatment was associated with a significant reduction in the probability of being gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26), transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means 0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the difference between ACT and non-artemisinin impact. The presence of slide-positive gametocytaemia prior to treatment significantly reduced ACT impact on gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia reduced estimates of ACT impact in a high transmission setting in Kenya, but not in a lower transmission setting in the Gambia. CONCLUSION Treatment with ACT significantly reduces infectiousness of individual patients with uncomplicated falciparum malaria compared to previous first line treatments. Rapid treatment of cases before gametocytaemia is well developed may enhance the impact of ACT on transmission.", "title": "Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials" }, { "docid": "9254550", "text": "BACKGROUND & OBJECTIVES Anaemia is commonly observed in children with malaria, but reports on leucocyte and platelet count abnormalities associated with malaria are inconsistent. This study examined the effect of age, gender, parasite density and temperature on haematological parameters in children with acute uncomplicated malaria. METHODS Haematological parameters were determined in children with acute uncomplicated malaria, and these were correlated with age, sex, temperature and parasite density. Statistical analysis was done using SAS 9.1. RESULTS Six hundred and ninety five children with acute uncomplicated malaria participated in the study. The mean age was 51.7 months +/- 33.8. At presentation, anaemia occurred in 43.8% of the patients and children <5 yr had a significantly lower haematocrit (28.4% +/- 4.8) than that of older children (32.8% +/- 4.8) (p <0.001), but the haematocrit was not significantly different by days 14 and 28. There was no difference between both sexes. Leucocytosis was more frequently seen than leucopenia (9.5% vs 3%). Thrombocytopenia was found in 59.3% of enrolled patients. More than half of the patients with thrombocytopenia had recovered by Day 28. Baseline platelet count was related to Day 14 (r = 0.6, p < 0.0001) and Day 28 (r = 0.2, p = 0.0015) and the haematocrit on Day 28 (r = 0.12, p = 0.00197). Platelet count showed no correlation with temperature, parasite density and leucocyte count. Haematocrit correlated with age (r = 0.4, p < 0.0001); but not with parasite density or temperature. Leucocyte count showed no correlation with age or parasite density. CONCLUSION While thrombocytopenia was the most common haematological finding and may be of diagnostic importance, anaemia and leucocytosis were more common in the under fives.", "title": "Age as a risk factor for thrombocytopenia and anaemia in children treated for acute uncomplicated falciparum malaria." }, { "docid": "25420421", "text": "Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.", "title": "Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome." }, { "docid": "3929361", "text": "BACKGROUND Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. METHOD AND FINDINGS A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. CONCLUSIONS The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination.", "title": "Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance" }, { "docid": "2264455", "text": "There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.", "title": "Vaccines against malaria" }, { "docid": "18174210", "text": "BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria. METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia. In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.", "title": "Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia" }, { "docid": "7486516", "text": "Asexuals are an important test case for theories of why species exist. If asexual clades displayed the same pattern of discrete variation as sexual clades, this would challenge the traditional view that sex is necessary for diversification into species. However, critical evidence has been lacking: all putative examples have involved organisms with recent or ongoing histories of recombination and have relied on visual interpretation of patterns of genetic and phenotypic variation rather than on formal tests of alternative evolutionary scenarios. Here we show that a classic asexual clade, the bdelloid rotifers, has diversified into distinct evolutionary species. Intensive sampling of the genus Rotaria reveals the presence of well-separated genetic clusters indicative of independent evolution. Moreover, combined genetic and morphological analyses reveal divergent selection in feeding morphology, indicative of niche divergence. Some of the morphologically coherent groups experiencing divergent selection contain several genetic clusters, in common with findings of cryptic species in sexual organisms. Our results show that the main causes of speciation in sexual organisms, population isolation and divergent selection, have the same qualitative effects in an asexual clade. The study also demonstrates how combined molecular and morphological analyses can shed new light on the evolutionary nature of species.", "title": "Independently Evolving Species in Asexual Bdelloid Rotifers" }, { "docid": "1805641", "text": "BACKGROUND Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas. METHODS AND FINDINGS We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting. CONCLUSIONS Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.", "title": "Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity" }, { "docid": "7734150", "text": "Pulmonary hypertension (PH) causes loss of body weight and inspiratory (diaphragm) muscle dysfunction. A model of PH induced by drug (monocrotaline, MCT) has been extensively used in mice to examine the etiology of PH. However, it is unclear if PH induced by MCT in mice reproduces the loss of body weight and diaphragm muscle dysfunction seen in patients. This is a pre-requisite for widespread use of mice to examine mechanisms of cachexia and diaphragm abnormalities in PH. Thus, we measured body and soleus muscle weight, food intake, and diaphragm contractile properties in mice after 6-8 weeks of saline (control) or MCT (600 mg/kg) injections. Body weight progressively decreased in PH mice, while food intake was similar in both groups. PH decreased (P<0.05) diaphragm maximal isometric specific force, maximal shortening velocity, and peak power. Protein carbonyls in whole-diaphragm lysates and the abundance of select myofibrillar proteins were unchanged by PH. Our findings show diaphragm isometric and isotonic contractile abnormalities in a murine model of PH induced by MCT. Overall, the murine model of PH elicited by MCT mimics loss of body weight and diaphragm muscle weakness reported in PH patients.", "title": "Diaphragm Atrophy and Contractile Dysfunction in a Murine Model of Pulmonary Hypertension" }, { "docid": "3770726", "text": "BACKGROUND Microfluidic platforms for quantitative evaluation of cell biologic processes allow low cost and time efficient research studies of biological and pathological events, such as monitoring cell migration by real-time imaging. In healthy and disease states, cell migration is crucial in development and wound healing, as well as to maintain the body's homeostasis. NEW METHOD The microfluidic chambers allow precise measurements to investigate whether fibroblasts carrying a mutation in the TOR1A gene, underlying the hereditary neurologic disease--DYT1 dystonia, have decreased migration properties when compared to control cells. RESULTS We observed that fibroblasts from DYT1 patients showed abnormalities in basic features of cell migration, such as reduced velocity and persistence of movement. COMPARISON WITH EXISTING METHOD The microfluidic method enabled us to demonstrate reduced polarization of the nucleus and abnormal orientation of nuclei and Golgi inside the moving DYT1 patient cells compared to control cells, as well as vectorial movement of single cells. CONCLUSION We report here different assays useful in determining various parameters of cell migration in DYT1 patient cells as a consequence of the TOR1A gene mutation, including a microfluidic platform, which provides a means to evaluate real-time vectorial movement with single cell resolution in a three-dimensional environment.", "title": "Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia." }, { "docid": "17925632", "text": "We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg (base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria (95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.", "title": "Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria." }, { "docid": "13959707", "text": "BACKGROUND Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) = 2.7 (95% CI 1.42, 5.01, P = 0.002) but not in those without detectable parasitaemia (HR = 1.0 (95% CI 0.74, 1.42, P = 0.9). CONCLUSIONS We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.", "title": "The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children" }, { "docid": "20221907", "text": "BACKGROUND Most gynecologists determine therapy based on current International Society of Gynecologic Pathologists (ISGP)/World Health Organization classification of endometrial hyperplasia, the reproducibility of which has been questioned. The Gynecologic Oncology Group (GOG) initiated a protocol to assess the efficacy of hormonal therapy of atypical endometrial hyperplasia (AEH). Primary goals of the first phase (Part A) were to prospectively determine reproducibility of referring institution's pathologist's diagnosis of AEH by a panel of 3 gynecologic pathologists and to determine reproducibility of diagnoses by panel members. METHODS Three hundred six women were entered on this protocol with a referring institution's pathologist diagnosis of AEH based on biopsy or curettage. Available slides were assessed independently and interpreted by each of a panel of 3 gynecologic pathologists who used International Society of Gynecologic Pathologists (ISGP)/World Health Organization criteria. The majority diagnosis was based on diagnostic concordance by at least 2 of the 3 panelists. RESULTS The referring institution's pathologist's diagnosis of AEH was supported by the majority of the panel in only 38% of cases. Overall kappa value for the panel diagnosis of AEH was 0.28. The majority diagnosis was adenocarcinoma in 29%, cycling endometrium in 7%, and nonatypical hyperplasia in 18% of cases. Unanimous agreement for any diagnosis was reached among all 3 of the panel in 40% of cases. For the panel, paired kappa values for any diagnosis ranged 0.34-0.43, with an overall kappa value of 0.40. CONCLUSION Reproducibility of referring institution's pathologists' diagnosis of AEH by a panel of gynecologic pathologists is poor. Both underestimation and overestimation of the severity of the lesion are very common. The level of reproducibility among subspecialist panel members for diagnosis of AEH in these specimens also is poor. Better criteria and better sampling are needed to improve reproducibility of this diagnosis, particularly if it is to be used for clinical decisions.", "title": "Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study." }, { "docid": "1852826", "text": "Interactions between hosts and parasites provide an ongoing source of selection that promotes the evolution of a variety of features in the interacting species. Here, we use a genetically explicit mathematical model to explore how patterns of gene expression evolve at genetic loci responsible for host resistance and parasite infection. Our results reveal the striking yet intuitive conclusion that gene expression should evolve along very different trajectories in the two interacting species. Specifically, host resistance loci should frequently evolve to co-express alleles, whereas parasite infection loci should evolve to express only a single allele. This result arises because hosts that co-express resistance alleles are able to recognize and clear a greater diversity of parasite genotypes. By the same token, parasites that co-express antigen or elicitor alleles are more likely to be recognized and cleared by the host, and this favours the expression of only a single allele. Our model provides testable predictions that can help interpret accumulating data on expression levels for genes relevant to host−parasite interactions.", "title": "Host–Parasite Interactions and the Evolution of Gene Expression" }, { "docid": "15194125", "text": "This study investigated interobserver (two observers) and intrasubject (two measurements) reproducibility of QT dispersion from abnormal electrocardiograms in patients with previous myocardial infarction, and compared a user-interactive with an automatic measurement system. Standard 12-lead electrocardiograms, recorded at 25 mm.s-1, were randomly chosen from 70 patients following myocardial infarction. These were scanned into a personal computer, and specially designed software skeletonized and joined each image. The images were then available for user-interactive (mouse and computer screen), or automatic measurements using a specially designed algorithm. For all methods reproducibility of the RR interval was excellent (mean absolute errors 3-4 ms, relative errors 0.3-0.5%). Reproducibility of the mean QT interval was good; intrasubject error was 6 ms (relative error 1.4%), interobserver error was 7 ms (1.8%), and observers' vs automatic measurement errors were 10 and 11 ms (2.5, 2.8%). However QTc dispersion measurements had large errors for all methods; intrasubject error was 12 ms (17.3%), interobserver error was 15 ms (22.1%), and observers' vs automatic measurement were errors 30 and 28 ms (35.4, 31.9%). QT dispersion measurements rely on the most difficult to measure QT intervals, resulting in a problem of reproducibility. Any automatic system must not only recognize common T wave morphologies, but also these more difficult T waves, if it is to be useful for measuring QT dispersion. The poor reproducibility of QT dispersion limits its role as a useful clinical tool, particularly as a predictor of events.", "title": "Reproducibility and automatic measurement of QT dispersion." }, { "docid": "26474812", "text": "Malaria parasites and immune responses in an infected human interact on a dynamic landscape, in which a population of replicating parasites depletes a population of replenishing red blood cells (RBCs). These underlying dynamics receive relatively little attention, but they offer unique insights into the processes that control most malaria infections. Here, we focus on the observation that three of the four malaria-parasite species that infect humans are restricted to particular age classes of RBC. We explicitly incorporate this observation in models of infection dynamics to distinguish common from species-specific pressures on host immune responses, and we find that age structuring has profound effects on the course of infection. For all four species conditions exist under which the parasites may persist at low densities, or may clear, even in the absence of an immune response. Catastrophic anemia can occur even with the two species that attack only the youngest RBCs, although only a small fraction of cells are parasitized at any point. Furthermore, with these two, compensatory erythropoetic responses in the host accelerate parasite population growth. A \"basic reproduction rate\" characterizes these differences in outcomes.", "title": "Age-structured red blood cell susceptibility and the dynamics of malaria infections." }, { "docid": "17168045", "text": "BACKGROUND This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging. METHODS The microcirculation in the rectal mucosa of adult patients with severe malaria was assessed by use of OPS imaging, at admission and then daily. Comparison groups comprised patients with uncomplicated falciparum malaria, patients with bacterial sepsis, and healthy individuals. RESULTS Erythrocyte velocities were measured directly in 43 adult patients with severe falciparum malaria, of whom 20 died. Microcirculatory blood flow was markedly disturbed, with heterogeneous obstruction that was proportional to severity of disease. Blocked capillaries were found in 29 patients (67%) and were associated with concurrent hyperdynamic blood flow (erythrocyte velocity, >750 mm/s) in adjacent vessels in 27 patients (93%). The proportion of blocked capillaries correlated with the base deficit in plasma and with the concentration of lactate. Abnormalities disappeared when the patients recovered. In healthy individuals and in patients with uncomplicated malaria or sepsis, no stagnant erythrocytes were detected, and, in patients with sepsis, hyperdynamic blood flow was prominent. CONCLUSION Patients with severe falciparum malaria show extensive microvascular obstruction that is proportional to the severity of the disease. This finding underscores the prominent role that microvascular obstruction plays in the pathophysiology of severe malaria and illustrates the fundamental difference between the microvascular pathophysiology of malaria and that of bacterial sepsis.", "title": "Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria." }, { "docid": "8133050", "text": "Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.", "title": "Quantifying Transmission Investment in Malaria Parasites" }, { "docid": "3930020", "text": "Epidermal Langerhans cells (LCs) play a key role in immune defense mechanisms and in numerous immunological disorders. In this report, we show that percutaneous infection of C57BL/6 mice with the helminth parasite Schistosoma mansoni leads to the activation of LCs but, surprisingly, to their retention in the epidermis. Moreover, using an experimental model of LC migration induced by tumor necrosis factor (TNF)-α, we show that parasites transiently impair the departure of LCs from the epidermis and their subsequent accumulation as dendritic cells in the draining lymph nodes. The inhibitory effect is mediated by soluble lipophilic factors released by the parasites and not by host-derived antiinflammatory cytokines, such as interleukin-10. We find that prostaglandin (PG)D2, but not the other major eicosanoids produced by the parasites, specifically impedes the TNF-α–triggered migration of LCs through the adenylate cyclase–coupled PGD2 receptor (DP receptor). Moreover, the potent DP receptor antagonist BW A868C restores LC migration in infected mice. Finally, in a model of contact allergen-induced LC migration, we show that activation of the DP receptor not only inhibits LC emigration but also dramatically reduces the contact hypersensitivity responses after challenge. Taken together, we propose that the inhibition of LC migration could represent an additional stratagem for the schistosomes to escape the host immune system and that PGD2 may play a key role in the control of cutaneous immune responses.", "title": "Role of the Parasite-Derived Prostaglandin D2 in the Inhibition of Epidermal Langerhans Cell Migration during Schistosomiasis Infection" }, { "docid": "20419913", "text": "The debate around the frequency and importance of genetic exchange in parasitic protozoa is now several decades old. Recently, fresh assertions have been made that predominant clonal evolution explains the population structures of several key protozoan pathogens. Here, we present an alternative perspective. On the assumption that much apparent clonality may be an artefact of inadequate sampling and study design, we review current research to define why sex might be so difficult to detect in protozoan parasite populations. In doing so, we contrast laboratory models of genetic exchange in parasitic protozoa with natural patterns of genetic diversity and consider the fitness advantage of sex at different evolutionary scales. We discuss approaches to improve the accuracy of efforts to characterize genetic exchange in the field. We also examine the implications of the first population genomic studies for the debate around sex and clonality in parasitic protozoa and discuss caveats for the future.", "title": "Reproductive clonality in protozoan pathogens--truth or artefact?" }, { "docid": "5289038", "text": "Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria, we estimated the effective propagation number, which reflects the relative importance of contrasting within-host control mechanisms through time and is sensitive to the inoculating parasite dose. Our analysis showed that the capacity of innate responses to restrict initial parasite growth saturates with parasite dose and that experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Such a statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.", "title": "Partitioning regulatory mechanisms of within-host malaria dynamics using the effective propagation number." }, { "docid": "24721347", "text": "The founding fathers of malariology combined scientific originality, perseverance in research, strong characters, breadth of interest and social concern. A hundred years later research and understanding has made immense progress but the world still bears a huge burden of malaria. For the next century research requires both more specialism and a holistic range if it is to be used in control, requiring multidisciplinary team work. Environmental changes and interventions produce a dynamic and changing pattern of malaria, not the static one of the past. From the original parasite life cycle, research has analysed a series of other cycles at electron microscope, biochemical and genome levels on decreasing size scales and quantitative epidemiological cycles for control. Recent additions to these concepts have been stage-specific antigens, cycles of disease rather than parasites alone, considering populations of parasites rather than just cases, and also genetic variation in each component of the parasite-human host-vector triad. In this volume there emerges for the first time a coherent overall picture of the biomedical aspects of basic malariology as the interacting population genetics of malaria parasites, anophelines and people. This provides a coherent model for the new century dealing with the great biological malaria problems of drug resistance, vaccine development, insecticidal and net control and can feed, with socio-economic work, into the gathering renewal of control efforts. New work on large-scale changes of malaria in space and time enables us to be precise about effects of local and global environmental changes to predict epidemics. Future research will be as much about linking these different scales of understanding as control will be about linking different levels of the health system. The grim situation in poor holoendemic countries also requires practical support of the type that the founders of malariology were involved in. A coherent understanding needs to feed into the new control efforts, from Roll Back Malaria onwards, for the next century.", "title": "The last and the next hundred years of malariology." }, { "docid": "20999249", "text": "BACKGROUND Falciparum malaria or malaria tropica is one of the leading causes of childhood mortality worldwide. Malaria-related deaths occur mainly in sub-Saharan Africa, where an estimated 365 million clinical cases of Plasmodium falciparum malaria occur each year. In Europe, imported malaria cases occur due to returning travellers or immigration mostly from African countries. Children are more at risk than adults. The objective of this study was to identify high risk groups for imported childhood malaria in Europe in order to guide development of strategies for prevention, early recognition and management. METHODS In the period May 2003-January 2005 we reviewed all cases of paediatric malaria in the Netherlands notified by the Dutch Paediatric Surveillance System (Nederland Signalerings Centrum Kindergeneeskunde, NSCK) and the literature on imported malaria in children in Europe published between 1996 and 2006. RESULTS Malaria occurred mainly in children of long-term (n = 15, 47%) and new (n = 8, 25%) immigrants and was mostly acquired in sub-Saharan Africa. The dominant species was P. falciparum. Only one quarter of children had used adequate malaria chemoprophylaxis. Complicated disease occurred in 10 (31%) of cases. We also reviewed the literature and found 6082 reported cases of imported malaria among children in Europe; among these, four died and only one was reported to develop neurological sequelae. CONCLUSION Imported malaria in children remains an important problem and is unlikely to decrease unless the reasons for inadequate prophylaxis are addressed.", "title": "Imported malaria in children: a national surveillance in the Netherlands and a review of European studies." } ]
1084	Side effects associated with antidepressants increases risk of stroke.	[ { "docid": "5691302", "text": "OBJECTIVES To investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose. DESIGN Cohort study of people aged 65 and over diagnosed as having depression. SETTING 570 general practices in the United Kingdom supplying data to the QResearch primary care database. PARTICIPANTS 60,746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008. MAIN OUTCOME MEASURES Hazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs. RESULTS 54,038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1,398,359 antidepressant prescriptions were issued: 764,659 (54.7%) for selective serotonin reuptake inhibitors, 442,192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189,305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants. CONCLUSIONS Selective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.", "title": "Antidepressant use and risk of adverse outcomes in older people: population based cohort study" } ]	[ { "docid": "24494539", "text": "OBJECTIVE To observe the clinical effects of acupuncture combined with auricular point sticking based on the western medication for post stroke depression (PSD). METHODS Sixty patients with PSD were randomly assigned into an acupuncture plus auricular application group (a combination group) and a medication group, 30 cases in each one. 20 mg paroxetine hydrochloride was prescribed orally in the medication group, once a day for continuous 8 weeks. Based on the above treatment, 30-minute acupuncture was used in the combination group for 8 weeks at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7), Neiguan (PC 6), Taichong (LR 3), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Fenglong (ST 40), once the other day and three times a week. Auricular point sticking therapy for 8 weeks was applied at shenmen (TF4), pizhixia (AT4), xin (CO15), and gan (CO12), with pressing 3 times a day and once 3-5 days. The total score and each factor scores of Hamilton's depression scale (HAMD) were observed in the two groups before and after treatment, and Asberg's antidepressant side-effect rating scale (SERS) and clinical effect were evaluated. RESULTS After treatment, the total HAMD scores of the two groups decreased compared with those before treatment (both P<0.05), with better effect in the combination group (P<0.05). The scores of the combination group after treatment were lower than those in the medication group, including the anxiety/somatization factor, sleep disturbance factor, hopelessness factor (all P<0.05). The total effective rate of the combination group was 86.7% (26/30), which was better than 66.7% (20/30) of the medication group (P<0.05). The SERS score of the combination group was lower than that of the medication group (P<0.05). CONCLUSIONS Acupuncture combined with auricular point sticking can improve the clinical symptoms and are effective and safe for PSD.", "title": "[Acupuncture combined with auricular point sticking therapy for post stroke depression:a randomized controlled trial]." }, { "docid": "8595678", "text": "BACKGROUND The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials. METHODS We established a collaboration of genetic studies consisting of 237 datasets including 59,995 individuals with data for homocysteine and 20,885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45,549 individuals, 2314 stroke events, 269 transient ischaemic attacks). FINDINGS The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 μmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 μmol/L, -0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1·00, 95% CI 0·90 to 1·11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0·78, 95% CI 0·68 to 0·90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region. INTERPRETATION In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677C→T and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption. FUNDING Full funding sources listed at end of paper (see Acknowledgments).", "title": "Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials" }, { "docid": "37424881", "text": "OBJECTIVE Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. DESIGN Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. SETTING The meta-analysis included fourteen randomized controlled trials, SUBJECTS A total of 39 420 patients. RESULTS Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification. CONCLUSIONS Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.", "title": "The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis." }, { "docid": "23627419", "text": "RATIONALE Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.", "title": "Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study." }, { "docid": "18256197", "text": "BACKGROUND AND PURPOSE The level of total homocysteine (tHcy) that confers a risk of ischemic stroke is unsettled, and no prospective cohort studies have included sufficient elderly minority subjects. We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke, myocardial infarction, and vascular death in a multiethnic prospective study. METHODS A population-based cohort was followed for vascular events (stroke, myocardial infarction, and vascular death). Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects (mean age, 69+/-10; 61% women, 53% Hispanics, 24% blacks, and 20% whites). Cox proportional models were used to calculate hazard ratios (HRs) and 95% CIs in tHcy categories after adjusting for age, race, education, renal insufficiency, B12 deficiency, and other risk factors. RESULTS The adjusted HR for a tHcy level > or =15 micromol/L compared with <10 micromol/L was greatest for vascular death (HR=6.04; 95% CI, 3.44 to 10.60), followed by combined vascular events (HR=2.27; 95% CI, 1.51 to 3.43), ischemic stroke (HR=2.01; 95% CI, 1.00 to 4.05), and nonvascular death (HR=2.02; 95% CI, 1.31 to 3.14). Mild to moderate elevations of tHcy of 10 to 15 micromol/L were not significantly predictive of ischemic stroke, but increased the risk of vascular death (2.27; 95% CI, 1.44 to 3.60) and combined vascular events (1.42; 95% CI, 1.06 to 1.88). The effect of tHcy was stronger among whites and Hispanics, but not a significant risk factor for blacks. CONCLUSIONS Total Hcy elevations above 15 micromol/L are an independent risk factor for ischemic stroke, whereas mild elevations of tHcy of 10 to 15 micromol/L are less predictive. The vascular effects of tHcy are greatest among whites and Hispanics, and less among blacks.", "title": "Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study." }, { "docid": "32328114", "text": "Stroke ranks as the third leading cause of death in the United States. It is now estimated that there are more than 700 000 incident strokes annually and 4.4 million stroke survivors.1 2 The economic burden of stroke was estimated by the American Heart Association to be $51 billion (direct and indirect costs) in 1999.3 Despite the advent of treatment of selected patients with acute ischemic stroke with tissue plasminogen activator and the promise of other experimental therapies, the best approach to reducing the burden of stroke remains prevention.4 5 High-risk or stroke-prone individuals can be identified and targeted for specific interventions.6 This is important because epidemiological data suggest a substantial leveling off of prior declines in stroke-related mortality and a possible increase in stroke incidence.7 8 The Stroke Council of the American Heart Association formed an ad hoc writing group to provide a clear and concise overview of the evidence regarding various established and potential stroke risk factors. The writing group was chosen based on expertise in specific subject areas, and it used literature review, reference to previously published guidelines, and expert opinion to summarize existing evidence and formulate recommendations (Table 1⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations As given in Tables 2 through 4⇓⇓⇓, risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented, less well documented).5 The tables give the estimated prevalence, population attributable risk, relative risk, and risk reduction with treatment for each factor when known. Population attributable risk reflects the proportion of ischemic strokes in the population that can be attributed to a particular risk factor and is given by the formula 100×[prevalence(relative risk−1)/prevalence(relative risk−1)+1]). …", "title": "Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association." }, { "docid": "14606752", "text": "OBJECTIVE To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches. DESIGN Meta-analysis. DATA SOURCES Medline, Embase, the Cochrane Trials Registry, and PsycLIT. Studies reviewed Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks. DATA EXTRACTION Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index. RESULTS 37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference -1.29, 95% confidence interval -2.18 to -0.39 and -0.70, -0.93 to -0.48) but not compared with selective serotonin reuptake inhibitors (-0.80, -2.63 to 0.02 and -0.20, -0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (β=-0.11, 95% confidence interval -0.63 to -0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97). CONCLUSIONS Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.", "title": "Tricyclic antidepressants and headaches: systematic review and meta-analysis" }, { "docid": "9813098", "text": "Young patients with an ischaemic stroke or transient ischaemic attack (TIA) often have no vascular risk factors. Hyperhomocysteinaemia is an established risk factor for stroke in elderly patients but it is uncertain whether it is also important for the prognosis of young ischaemic stroke and TIA patients. We examined the possible effect of the plasma homocysteine level on the risk of recurrent vascular events in patients between 18 and 45 years of age. The study population consisted of 161 consecutive patients with a recent cerebral infarction or TIA. Data on the primary event and the homocysteine level were collected retrospectively from hospital records. General practitioners and patients were contacted by telephone to record vascular events and the type of medication used during the follow–up period. Vascular events included cerebral infarction, TIA, pulmonary embolism, venous thrombosis, myocardial infarction and peripheral arterial disease. A Kaplan- Meier curve showed a dose effect relationship between event-free survival time and tertiles of the homocysteine level (Log rank statistic 5.91; p = 0.05). The Cox hazard ratio, after adjustment for homocysteine lowering treatment, was 1.7 (95 % CI, 1.1 to 2.8) for any vascular outcome event, 1.9 (95% CI, 1.1 to 3.0) for arterial outcome events and 1.8 (95 % CI, 1.1 to 2.9) for cerebral outcome events. In spite of our small number of outcome events we found a significant association at the 95% confidence level between homocysteine level and the risk of recurrent vascular events in young patients with an ischaemic stroke or TIA. The association is of the same magnitude as in elderly people.", "title": "Plasma homocysteine is a risk factor for recurrent vascular events in young patients with an ischaemic stroke or TIA" }, { "docid": "37619697", "text": "BACKGROUND Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study. METHODS Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient. RESULTS There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants. CONCLUSIONS The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.", "title": "Phenylpropanolamine and the risk of hemorrhagic stroke." }, { "docid": "14566771", "text": "The relationship of migraine and stroke is complex. Stroke may be coincidental with migraine but migraine may confer an increased risk of stroke in women under 45 years of age and possibly in men who have migraine with aura. Stroke may mimic migraine but migraine syndromes may be symptomatic of underlying cerebrovascular disorders. True migraine-induced stroke is rare. The mechanisms of stroke induced during a migraine attack remain to be determined but probably involve an interaction between the dynamic shifts in cerebral blood flow and stroke risk factors.", "title": "Stroke and migraine--the spectrum of cause and effect." }, { "docid": "37065914", "text": "BACKGROUND AND PURPOSE Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. METHODS Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. RESULTS Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, <0.05). In multivariate analysis, men in the lowest quartile of serum soluble corin were more likely to have ischemic (odds ratio [OR], 4.90; 95% confidence interval, 2.99-8.03) and hemorrhagic (OR, 17.57; 95% confidence interval, 4.85-63.71) stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, <0.001). CONCLUSIONS Serum soluble corin was decreased in patients with stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke.", "title": "Serum Soluble Corin is Decreased in Stroke." }, { "docid": "15984735", "text": "OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.", "title": "Migraine and cardiovascular disease: systematic review and meta-analysis." }, { "docid": "39281140", "text": "CONTEXT Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. OBJECTIVE To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. DESIGN, SETTING, AND PATIENTS Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. INTERVENTION Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. MAIN OUTCOME MEASURES The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). RESULTS Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. CONCLUSION In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.", "title": "Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial." }, { "docid": "6083952", "text": "1. Incubation of LMCAT fibroblast cells with antidepressants potentiates glucocorticoid receptor (GR)-mediated gene transcription in the presence of dexamethasone and cortisol, but not of corticosterone. We have shown that antidepressants do so by inhibiting the LMCAT cell membrane steroid transporter (which is virtually identical to the multidrug resistance P-glycoprotein) and thus by increasing dexamethasone or cortisol intracellular concentrations. However, previous experiments with the antidepressant fluoxetine in the presence of dexamethasone have produced negative results (Pariante et al. (2001). Br. J. Pharmacol., 134, 1335-1343). 2. We have since re-examined the effects of fluoxetine on GR-mediated gene transcription in the presence of dexamethasone. Moreover, we have examined the effects of fluoxetine on GR-mediated gene transcription in the presence of cortisol and corticosterone, and on the intracellular accumulation of radioactive cortisol and corticosterone. Finally, we have examined the effects of fluoxetine on inhibition of P-glycoprotein activity in Caco-2 cells. 3. We now find that fluoxetine (1-10 micro M) enhances GR-mediated gene transcription in the presence of dexamethasone and cortisol (+140-170%), but not of corticosterone, and increases the intracellular accumulation of (3)H-cortisol (+5-15%), but not of (3)H-corticosterone. Moreover, fluoxetine (10 micro M) induces approximately 30% inhibition of PGP activity in Caco-2 cells. 4. Our results show that fluoxetine, like other antidepressants, inhibits membrane steroid transporters.", "title": "Antidepressant fluoxetine enhances glucocorticoid receptor function in vitro by modulating membrane steroid transporters." }, { "docid": "16180601", "text": "OBJECTIVE Serum soluble corin has been associated with stroke. However, whether it is associated with stroke prognosis has not yet been studied. Therefore, we aimed to study the association of serum soluble corin with risk of poor outcomes within 3 months after stroke. METHODS We followed 522 stroke patients for 3 months to identify major disability, death and vascular events. Serum soluble corin was measured at baseline for all participants. Logistic regression was used to examine the associations of baseline serum soluble corin with outcomes of stroke, adjusting for age, sex, baseline NIHSS score, hours from onset to hospitalization, smoking, drinking, hypertension, diabetes, coronary heart disease, atrial fibrillation, family history of stroke, and stroke subtype. RESULTS Patients with high corin had a significantly lower crude risk for the composite outcome of major disability or death (OR = 0.64, 95%CI: 0.43-0.96) than patients with low corin (the lowest tertile). After adjustment for age and baseline NIHSS score, patients with high corin still had a significantly lower risk for the composite outcome of major disability or death (OR = 0.60, 95%CI: 0.36-0.99). This association became bottom line significant after additionally adjusting for other conventional factors (OR = 0.61, P = 0.058). No association was found between serum soluble corin and other composite outcomes. CONCLUSION Serum soluble corin deficiency predicted risk for major disability within 3 months after stroke, independent of baseline neurological deficient. Our results may indicate a probable role of corin in stroke prognosis.", "title": "Serum Soluble Corin Deficiency Predicts Major Disability within 3 Months after Acute Stroke" }, { "docid": "5551138", "text": "This article reviews the efficacy of nortriptyline for smoking cessation based on a meta-analysis of the Cochrane Library. Six placebo-controlled trials have shown nortriptyline (75-100 mg) doubles quit rates (OR = 2.1). Between 4% and 12% of smokers dropped out because of adverse events, but no serious adverse events occurred. The efficacy of nortriptyline did not appear to be related to its antidepressant actions. Nortriptyline is an efficacious aid to smoking cessation with a magnitude of effect similar to that for bupropion and nicotine replacement therapies. Whether nortriptyline produces serious side effects at these doses in healthy, nondepressed smokers remains unclear because it has been tested in only 500 smokers. The finding that nortriptyline and bupropion are effective for smoking cessation but that selective serotonin-reuptake inhibitors are not suggests that dopaminergic or adrenergic, but not serotonergic, activity is important for cessation efficacy. Until further studies can verify a low incidence of significant adverse events, nortriptyline should be a second-line treatment for smoking cessation.", "title": "Nortriptyline for smoking cessation: a review." }, { "docid": "21571708", "text": "CONTEXT Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.", "title": "Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality." }, { "docid": "3868322", "text": "Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels. Allelic CETP mRNA expression ratios in 56 human livers were strongly associated with several variants 2.5-7 kb upstream of the transcription start site (e.g., rs247616 p = 6.4 × 10(-5), allele frequency 33%). In addition, a common alternatively spliced CETP isoform lacking exon 9 (Δ9), has been shown to prevent CETP secretion in a dominant-negative manner. The Δ 9 expression ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p = 6.8 × 10(-10)) and intron 8 polymorphism rs9930761-T>C (5.6 × 10(-8)) (in high linkage disequilibrium with allele frequencies 6-7%). rs9930761 changes a key splicing branch point nucleotide in intron 8, while rs5883 alters an exonic splicing enhancer sequence in exon 9.The effect of these polymorphisms was evaluated in two clinical studies. In the Whitehall II study of 4745 subjects, both rs247616 and rs5883T/rs9930761C were independently associated with increased HDL-C levels in males with similar effect size (rs247616 p = 9.6 × 10(-28) and rs5883 p = 8.6 × 10(-10), adjusted for rs247616). In an independent multiethnic US cohort of hypertensive subjects with CAD (INVEST-GENE), rs5883T/rs9930761C alone were significantly associated with increased incidence of MI, stroke, and all-cause mortality in males (rs5883: OR 2.36 (CI 1.29-4.30), p = 0.005, n = 866). These variants did not reach significance in females in either study. Similar to earlier results linking low CETP activity with poor outcomes in males, our results suggest genetic, sex-dependent CETP splicing effects on cardiovascular risk by a mechanism independent of circulating HDL-C levels.", "title": "Cholesteryl Ester Transfer Protein (CETP) Polymorphisms Affect mRNA Splicing, HDL Levels, and Sex-Dependent Cardiovascular Risk" }, { "docid": "1495563", "text": "OBJECTIVE To observe the therapeutic effect of \"Xingnao Kaiqiao Zhenfa\" (Acupuncture Technique for Restoring Consciousness) in the treatment of post-stroke depression. METHODS A total of 256 stroke patients were divided into acupuncture group (n = 180, male 138, female 42) and medication group (n = 76, male 57 and female 19) according to their visiting sequence to our hospital. Acupoints used were Neiguan (PC 6), Renzhong (GV 26), Baihui (GV 20), Yintang (EX-HN 3) and Sanyinjiao (SP 6,the affected side) and the needles were retained for 20 min every time. Patients of medication group were asked to take Amitriptyline (50 mg/d at first, 200 mg/d). Acupuncture treatment was conducted twice daily, and after one month's treatment the therapeutic effect was evaluated. Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HRSD) were used to assess the patient's state of depression. RESULTS After the treatment, of the 180 and 76 cases in acupuncture and medication groups, 31 (17.2%) and 13 (17.1%) were cured, 73 (40.6%) and 18 (23.7%) had a marked improvement in their depression state, 27 (15.0%) and 12 (15.8%) had an improvement, 49 (27.2%) and 33 (43.4%) failed, with the effective rates being 72.8% and 56.6% respectively. The markedly effective rate and the total effective rate of acupuncture group were significantly higher than those of medication group (P < 0.05). After the treatment, the total scores of SDS and HRSD and the severity index of two groups decreased pronouncedly in comparison with those of their individual pre-treatment; and the therapeutic effects of acupuncture group were significantly better than those of medication group in reducing SDS, HRSD and severity index (P < 0 .05). In addition, the decreased values of depression, pessimistic mood and irritability of acupuncture group were all bigger than those of medication group (P < 0.05). No significant difference was found between two groups in the decreased value of insomnia (P > 0.05). CONCLUSION \"Acupuncture Technique for Restoring Consciousness\" can effectively improve depression patients' symptoms and the therapeutic effect of acupuncture is markedly superior to that of medication for post-stroke patients.", "title": "[Clinical study on the therapeutic effect of acupuncture in the treatment of post-stroke depression]." }, { "docid": "14827874", "text": "CONTEXT For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. EVIDENCE ACQUISITION We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders. CONCLUSIONS Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.", "title": "0021-972X/06/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 91(3):760–771 Printed in U.S.A. Copyright © 2006 by The Endocrine Society doi: 10.1210/jc.2005-1923 REVIEW: Aromatase Inhibitors for Ovulation Induction" }, { "docid": "1428840", "text": "BACKGROUND It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.", "title": "Case-control study of endogenous steroid hormones and endometrial cancer." }, { "docid": "10984005", "text": "CONTEXT More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.", "title": "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults." }, { "docid": "16701509", "text": "BACKGROUND The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. METHODS In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38,823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. RESULTS During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P(trend) =.02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI > or =25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P(trend)<.001; P(interaction) =.001). CONCLUSION Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.", "title": "Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk." }, { "docid": "11718220", "text": "BACKGROUND Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke. METHODS In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533. FINDINGS All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27). INTERPRETATION These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results. FUNDING Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.", "title": "Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial" }, { "docid": "13097856", "text": "CONTEXT In 2002, an estimated 877,000 lives were lost worldwide through suicide. Some developed nations have implemented national suicide prevention plans. Although these plans generally propose multiple interventions, their effectiveness is rarely evaluated. OBJECTIVES To examine evidence for the effectiveness of specific suicide-preventive interventions and to make recommendations for future prevention programs and research. DATA SOURCES AND STUDY SELECTION Relevant publications were identified via electronic searches of MEDLINE, the Cochrane Library, and PsychINFO databases using multiple search terms related to suicide prevention. Studies, published between 1966 and June 2005, included those that evaluated preventative interventions in major domains; education and awareness for the general public and for professionals; screening tools for at-risk individuals; treatment of psychiatric disorders; restricting access to lethal means; and responsible media reporting of suicide. DATA EXTRACTION Data were extracted on primary outcomes of interest: suicidal behavior (completion, attempt, ideation), intermediary or secondary outcomes (treatment seeking, identification of at-risk individuals, antidepressant prescription/use rates, referrals), or both. Experts from 15 countries reviewed all studies. Included articles were those that reported on completed and attempted suicide and suicidal ideation; or, where applicable, intermediate outcomes, including help-seeking behavior, identification of at-risk individuals, entry into treatment, and antidepressant prescription rates. We included 3 major types of studies for which the research question was clearly defined: systematic reviews and meta-analyses (n = 10); quantitative studies, either randomized controlled trials (n = 18) or cohort studies (n = 24); and ecological, or population- based studies (n = 41). Heterogeneity of study populations and methodology did not permit formal meta-analysis; thus, a narrative synthesis is presented. DATA SYNTHESIS Education of physicians and restricting access to lethal means were found to prevent suicide. Other methods including public education, screening programs, and media education need more testing. CONCLUSIONS Physician education in depression recognition and treatment and restricting access to lethal methods reduce suicide rates. Other interventions need more evidence of efficacy. Ascertaining which components of suicide prevention programs are effective in reducing rates of suicide and suicide attempt is essential in order to optimize use of limited resources.", "title": "Suicide prevention strategies: a systematic review." }, { "docid": "6945285", "text": "OBJECTIVE To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease. DESIGN Double blind placebo controlled randomised trial. SETTING 85 general practices and nine hospital vascular clinics. PARTICIPANTS 1568 men, mean age 68.2 years (range 35 to 92) at recruitment. INTERVENTIONS Bezafibrate 400 mg daily (783 men) or placebo (785 men). MAIN OUTCOME MEASURES Combination of coronary heart disease and of stroke. All coronary events, fatal and non-fatal coronary events separately, and strokes alone (secondary end points). RESULTS Bezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged <65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years. CONCLUSIONS Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged <65 years at entry, in whom all coronary events may also be reduced.", "title": "Bezafibrate in men with lower extremity arterial disease: randomised controlled trial." }, { "docid": "12438901", "text": "BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.", "title": "Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial" }, { "docid": "6191684", "text": "CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects. OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches. DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53). MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group. RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.", "title": "Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial." }, { "docid": "6327940", "text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.", "title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity." }, { "docid": "13883546", "text": "The term antidepressant refers to a drug that helps to rectify specific biological abnormalities that give rise to the symptoms of depression. This exemplifies what we have called the “disease-centred” model of psychotropic drug action [ 1]. Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms. In contrast, we propose in this Essay that an alternative “drug-centred” model can better explain observed drug effects in psychiatric conditions. This drug-centred model suggests that instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms ( Table 1). Alcohol's disinhibiting effects may relieve symptoms of social phobia, but that does not imply that alcohol corrects a chemical imbalance underlying social phobia. Sedation may lessen high arousal, present in many acute psychiatric situations. Drugs that induce indifference, such as neuroleptics or opiates, may help reduce the distress of acute psychotic symptoms. Low-dose stimulants may help improve attention and concentration in the short term. Table 1 Main Assumptions of Two Models of Psychotropic Drug Action The disease-centred model in psychiatry leads researchers to infer antidepressant effects from patients' scores on symptom rating scales presumed to assess the manifestations of the disease. The drug-centred model, on the other hand, suggests that physiological and subjective effects of drugs should be examined in their own right. These effects include various forms of sedation, stimulation, and a plethora of biopsychological states. Depending on individual inclination and context (including a person's emotional state upon drug ingestion), intoxication with some drugs produces euphoria or mood elevation. Because tolerance develops, however, euphoriant effects do not persist with long-term use. If antidepressants or any other psychotropic drugs could be shown to have mood-elevating effects that were long-term and not diminished by being in a depressed emotional state, this would distinguish them from psychotropic drugs that cause euphoria and might prove uniquely useful in depressed patients (see Sidebar).", "title": "Do Antidepressants Cure or Create Abnormal Brain States?" } ]
PLAIN-1649	Monsanto	[ { "docid": "MED-1733", "text": "INTRODUCTION: Glyphosate-surfactant herbicide (GlySH) is widely used as a non-selective herbicide. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Intramuscular injection of GlySH has never been reported. We present a case of GlySH intoxication via intramuscular injection. CASE REPORT: A 42-year-old woman came to the emergency department complaining of painful swelling of left upper limb for 12 h. She had performed an intramuscular injection of 6 mL of GlySH over the lateral aspect of the left elbow 15 h previously. Physical examination disclosed painful swelling over left distal arm, elbow, and forearm with three needle punctures. CT scan revealed ill-defined areas of heterogeneous high density with marked swelling at subcutaneous tissue over posterior aspect of the elbow. DISCUSSION: The mechanism of toxicity of GlySH is complicated and surfactant was thought to play an important role in GlySH intoxication. Intramuscular GlySH poisoning is different from oral GlySH intoxication. Care should be taken when monitoring acute rhabdomyolysis and compartment syndrome, which may develop rapidly and contribute to the surfactant component of glyphosate formulation.", "title": "Rhabdomyolysis from an intramuscular injection of glyphosate-surfactant herbicide." }, { "docid": "MED-3935", "text": "Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.", "title": "Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007" }, { "docid": "MED-1744", "text": "Eighty percent of (commercial) genetically engineered seeds (GES) are designed only to resist herbicides. Letting farmers use more chemicals, they cut labor costs. But developing nations say GES cause food shortages, unemployment, resistant weeds, and extinction of native cultivars when \"volunteers\" drift nearby. While GES patents are reasonable, this paper argues many patent policies are not. The paper surveys GE technology, outlines John Locke's classic account of property rights, and argues that current patent policies must be revised to take account of Lockean ethical constraints. After answering a key objection, it provides concrete suggestions for implementing its ethical conclusions.", "title": "Property rights and genetic engineering: developing nations at risk." }, { "docid": "MED-1729", "text": "We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed.", "title": "Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA." }, { "docid": "MED-1740", "text": "To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.", "title": "Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation." }, { "docid": "MED-1736", "text": "Glyphosate is a herbicide widely used to kill weeds both in agricultural and non-agricultural landscapes. Its reproductive toxicity is related to the inhibition of a StAR protein and an aromatase enzyme, which causes an in vitro reduction in testosterone and estradiol synthesis. Studies in vivo about this herbicide effects in prepubertal Wistar rats reproductive development were not performed at this moment. Evaluations included the progression of puberty, body development, the hormonal production of testosterone, estradiol and corticosterone, and the morphology of the testis. Results showed that the herbicide (1) significantly changed the progression of puberty in a dose-dependent manner; (2) reduced the testosterone production, in semineferous tubules' morphology, decreased significantly the epithelium height (P < 0.001; control = 85.8 +/- 2.8 microm; 5 mg/kg = 71.9 +/- 5.3 microm; 50 mg/kg = 69.1 +/- 1.7 microm; 250 mg/kg = 65.2 +/- 1.3 microm) and increased the luminal diameter (P < 0.01; control = 94.0 +/- 5.7 microm; 5 mg/kg = 116.6 +/- 6.6 microm; 50 mg/kg = 114.3 +/- 3.1 microm; 250 mg/kg = 130.3 +/- 4.8 microm); (4) no difference in tubular diameter was observed; and (5) relative to the controls, no differences in serum corticosterone or estradiol levels were detected, but the concentrations of testosterone serum were lower in all treated groups (P < 0.001; control = 154.5 +/- 12.9 ng/dL; 5 mg/kg = 108.6 +/- 19.6 ng/dL; 50 mg/dL = 84.5 +/- 12.2 ng/dL; 250 mg/kg = 76.9 +/- 14.2 ng/dL). These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.", "title": "Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology." }, { "docid": "MED-3940", "text": "Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.", "title": "Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease" }, { "docid": "MED-1749", "text": "Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada." }, { "docid": "MED-3937", "text": "BACKGROUND: The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. METHODS: A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. RESULTS: Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called \"the magic potion\". CONCLUSIONS: Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).", "title": "Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books." }, { "docid": "MED-1743", "text": "This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \"chemical\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \"substantial non-equivalence\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.", "title": "Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans." }, { "docid": "MED-4726", "text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.", "title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies." }, { "docid": "MED-1732", "text": "Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Glyphosate induces human breast cancer cells growth via estrogen receptors." }, { "docid": "MED-1728", "text": "The United States Environmental Protection Agency and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. Glyphosate is widely considered by regulatory authorities and scientific bodies to have no carcinogenic potential, based primarily on results of carcinogenicity studies of rats and mice. To examine potential cancer risks in humans, we reviewed the epidemiologic literature to evaluate whether exposure to glyphosate is associated causally with cancer risk in humans. We also reviewed relevant methodological and biomonitoring studies of glyphosate. Seven cohort studies and fourteen case-control studies examined the association between glyphosate and one or more cancer outcomes. Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate. Data from biomonitoring studies underscore the importance of exposure assessment in epidemiologic studies, and indicate that studies should incorporate not only duration and frequency of pesticide use, but also type of pesticide formulation. Because generic exposure assessments likely lead to exposure misclassification, it is recommended that exposure algorithms be validated with biomonitoring data. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Epidemiologic studies of glyphosate and cancer: a review." }, { "docid": "MED-1741", "text": "Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.", "title": "Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase" }, { "docid": "MED-1737", "text": "Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.", "title": "Time- and dose-dependent effects of roundup on human embryonic and placental cells." }, { "docid": "MED-1731", "text": "Glyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.", "title": "Glyphosate herbicide formulation: a potentially lethal ingestion." }, { "docid": "MED-1725", "text": "Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable. Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these \"potentially carcinogenic\" pesticides suggested a positive trend of risk with exposure to increasing numbers. Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.", "title": "Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men" }, { "docid": "MED-1745", "text": "The composition of glyphosate-tolerant (Roundup Ready) soybean 40-3-2 was compared with that of conventional soybean grown in Romania in 2005 as part of a comparative safety assessment program. Samples were collected from replicated field trials, and compositional analyses were performed to measure proximates (moisture, fat, ash, protein, and carbohydrates by calculation), fiber, amino acids, fatty acids, isoflavones, raffinose, stachyose, phytic acid, trypsin inhibitor, and lectin in grain as well as proximates and fiber in forage. The mean values for all biochemical components assessed for Roundup Ready soybean 40-30-2 were similar to those of the conventional control and were within the published range observed for commercial soybean. The compositional profile of Roundup Ready soybean 40-3-2 was also compared to that of conventional soybean varieties grown in Romania by calculating a 99% tolerance interval to describe compositional variability in the population of traditional soybean varieties already on the marketplace. These comparisons, together with the history of the safe use of soybean as a common component of animal feed and human food, lead to the conclusion that Roundup Ready soybean 40-3-2 is compositionally equivalent to and as safe and nutritious as conventional soybean varieties grown commercially.", "title": "Chemical composition of glyphosate-tolerant soybean 40-3-2 grown in Europe remains equivalent with that of conventional soybean (Glycine max L.)." }, { "docid": "MED-3938", "text": "Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.", "title": "Association between polychlorinated biphenyls and Parkinson’s disease neuropathology" }, { "docid": "MED-3939", "text": "Excerpt This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) on the treatment of TBI in U.S. hospitals in 2004. Hospital utilization and costs for TBI admissions are compared with hospital stays for all other injuries. Additionally, trends in hospital stays for TBI and differences in the distribution of TBI admissions by various patient characteristics are examined. Finally, common causes of TBIs resulting in hospital admission, as well as the coexisting conditions often associated with these injuries, are described. All differences between estimates noted in the text are statistically significant at the 0.05 level or better.", "title": "Hospital Admissions for Traumatic Brain Injuries, 2004: Statistical Brief #27" }, { "docid": "MED-1739", "text": "Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by opening L-type voltage-dependent Ca(2+) channels as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased (45)Ca(2+) uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca(2+) influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate-Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, γ-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells." }, { "docid": "MED-2763", "text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.", "title": "Facing the facelessness of public health: what's the public got to do with it?" }, { "docid": "MED-1730", "text": "The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease. Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Epidemiologic studies of glyphosate and non-cancer health outcomes: a review." }, { "docid": "MED-1726", "text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.", "title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles" }, { "docid": "MED-1746", "text": "The global area covered with transgenic (genetically modified) crops has rapidly increased since their introduction in the mid-1990s. Most of these crops have been rendered herbicide resistant, for which it can be envisaged that the modification has an impact on the profile and level of herbicide residues within these crops. In this article, the four main categories of herbicide resistance, including resistance to acetolactate-synthase inhibitors, bromoxynil, glufosinate and glyphosate, are reviewed. The topics considered are the molecular mechanism underlying the herbicide resistance, the nature and levels of the residues formed and their impact on the residue definition and maximum residue limits (MRLs) defined by the Codex Alimentarius Commission and national authorities. No general conclusions can be drawn concerning the nature and level of residues, which has to be done on a case-by-case basis. International residue definitions and MRLs are still lacking for some herbicide-crop combinations, and harmonisation is therefore recommended. Copyright © 2011 Society of Chemical Industry.", "title": "The impact of altered herbicide residues in transgenic herbicide-resistant crops on standard setting for herbicide residues." }, { "docid": "MED-3936", "text": "Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.", "title": "Elevated Serum Pesticide Levels and Risk of Parkinson Disease" }, { "docid": "MED-1738", "text": "Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.", "title": "Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis." } ]	[ { "docid": "MED-4059", "text": "2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.", "title": "Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans." }, { "docid": "MED-760", "text": "There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses.", "title": "A High Antioxidant Spice Blend Attenuates Postprandial Insulin and Triglyceride Responses and Increases Some Plasma Measures of Antioxidant Activity in Healthy, Overweight Men" }, { "docid": "MED-4034", "text": "OBJECTIVES: To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men. DESIGN: Prospective, observational study. SETTING: Greater Boston, Massachusetts, metropolitan area. PARTICIPANTS: Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study. MEASUREMENTS: Dental and physical examinations were conducted every 3 to 5 years. Diet was assessed using food frequency questionnaires (FFQs). Mean follow-up was 15 years (range: 2-24 years). Periodontal disease progression on each tooth was defined as alveolar bone loss (ABL) advancement of 40% or more, probing pocket depth (PPD) of 2 mm or more, or tooth loss. Good and excellent fiber sources provided 2.5 g or more of fiber per serving. Multivariate proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of periodontal disease progression and tooth loss in relation to fiber sources, stratified according to age younger than 65 versus 65 and older, and controlled for smoking, body mass index, calculus, baseline periodontal disease level, caries, education, exercise, carotene, thiamin and caffeine intake, and tooth brushing. RESULTS: In men aged 65 and older, each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression (HR = 0.76, 95% CI = 0.60-0.95) and tooth loss (HR = 0.72, 95% CI = 0.53-0.97). Of the different food groups, only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL (HR = 0.86 per serving, 95% CI = 0.78-0.95), PPD (HR = 0.95, 95% CI = 0.91-0.99), and tooth loss (HR = 0.88, 95% CI = 0.78-0.99). No significant associations were seen in men younger than 65. CONCLUSION: Benefits of higher intake of high-fiber foods, especially fruits, on slowing periodontal disease progression are most evident in men aged 65 and older. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.", "title": "High-fiber foods reduce periodontal disease progression in men aged 65 and older: the Veterans Affairs normative aging study/Dental Longitudinal St..." }, { "docid": "MED-1793", "text": "Most research studies in the field of dietary polyphenols or phenolic compounds use a chemical approach focusing exclusively on polyphenols extracted from plant foods with organic solvents. However, an appreciable part of polyphenols are not extracted with organic solvents and thus are ignored in biological, nutritional, and epidemiological studies. Recent studies have shown that these nonextractable polyphenols (NEPP) are a major part of total dietary polyphenols and that they exhibit a significant biological activity. A physiological approach is proposed on the basis that the bioavailability and health-related properties of polyphenols depend on their solubility in intestinal fluids, which is different from their solubility in organic solvents. This paper tries to clarify the concept of NEPP, distinguishing between chemical and physiological approaches and pointing out the main qualitative and quantitative differences between them. It is stressed that the literature and databases refer to only extractable polyphenols. Greater attention to NEPP may fill the current gap in the field of dietary polyphenols.", "title": "Concept and health-related properties of nonextractable polyphenols: the missing dietary polyphenols." }, { "docid": "MED-980", "text": "Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Trial Registration Controlled-Trials.com ISRCTN94410159", "title": "Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial" }, { "docid": "MED-3977", "text": "OBJECTIVE: The aim of this study was to revisit findings from previous studies reporting that pet ownership improves outcome following an admission for acute coronary syndrome (ACS). METHOD: Four hundred and twenty-four patients admitted to a cardiac unit with an ACS completed questions regarding pet ownership in hospital. Rates of cardiac death and readmission were assessed 1 year following hospitalization. RESULTS: Pet owners were more likely to experience a death or readmission following their hospitalization, after controlling for key psychosocial and medical covariates. When dog and cat owners were considered separately, cat ownership was significantly associated with increased risk of death or readmission. CONCLUSION: In this independent study, pet ownership at baseline, and cat ownership in particular, was associated with increased cardiac morbidity and mortality in the year following an admission for an acute coronary syndrome, a finding contrary to previous reports.", "title": "Survival following an acute coronary syndrome: a pet theory put to the test." }, { "docid": "MED-3734", "text": "Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.", "title": "Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants." }, { "docid": "MED-2511", "text": "Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \"functional foods\" and, indeed, are currently being explored for their potential health-enhancing properties.", "title": "The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load." }, { "docid": "MED-3022", "text": "Methylmercury (MM) is a very potent neurotoxic agent. Its role in polluting the environment is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. Exposure to MM may be through ingestion of poisoned fish or inadvertent misuse of grain treated with the poison as a fungicide. Major epidemics have occurred in Japan (Fetal Minamata disease), Iraq, Pakistan, Guatemala, and Ghana. Sporadic incidences have occurred in the United States and Canada. There is no effective antidote to counteract the effect of MM on the central nervous system, although the information documented should provide hope for more effective therapy in acute cases.", "title": "The many faces of methylmercury poisoning." }, { "docid": "MED-1890", "text": "BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological s searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.", "title": "Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis." }, { "docid": "MED-3024", "text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon." }, { "docid": "MED-2090", "text": "Taking into consideration genetic damage plays an important role in carcinogenesis, the purpose of this paper is to provide an overview on the genotoxic potential of some endodontic compounds currently used in dentistry, such as formocresol, paramonochlorophenol, calcium hydroxide, resin-based sealers, phenolic compounds, chlorhexidine, mineral trioxide aggregate, and others. Some of these compounds appear capable of exerting noxious activity on the genetic material. The action mechanisms are discussed. Therefore, this is an area that warrants investigation since the estimation of risk of these substances with respect to genotoxicity will be added to those used for regulatory purposes in improving oral health and preventing oral carcinogenesis.", "title": "Do endodontic compounds induce genetic damage? A comprehensive review." }, { "docid": "MED-4593", "text": "AIMS: The objective of the study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) contamination of retail meat and to determine the level of contamination. METHODS AND RESULTS: Pork (pork chops and ground pork), ground beef and chicken (legs, wings and thighs) were purchased at retail outlets in four Canadian provinces and tested for the presence of methicillin-resistant Staph. aureus using qualitative and quantitative methods. MRSA was isolated from 9.6% of pork, 5.6% of beef and 1.2% of chicken samples (P = 0.0002). Low levels of MRSA were typically present, with 37% below the detection threshold for quantification and <100 CFU g(-1) present in most quantifiable samples. All isolates were classified as Canadian epidemic MRSA-2 (CMRSA-2) by pulsed field gel electrophoresis (PFGE), with two different PFGE subtypes, and were spa type 24/t242. CONCLUSIONS: MRSA contamination of retail meat is not uncommon. While CMRSA-2, a human epidemic clone, has been found in pigs in Canada, the lack of isolation of livestock-associated ST398 was surprising. SIGNIFICANCE AND IMPACT OF THE STUDY: The relevance of MRSA contamination of meat is unclear but investigation is required because of the potential for exposure from food handling. Sources of contamination require investigation because these results suggest that human or animal sources could be involved.", "title": "Detection and quantification of methicillin-resistant Staphylococcus aureus (MRSA) clones in retail meat products." }, { "docid": "MED-2969", "text": "OBJECTIVE: We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-kappaB (NF-kappaB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose. RESEARCH DESIGN AND METHODS: Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected. RESULTS: There was a significant increase in ROS generation by mononuclear cells (by 130 +/- 18%, P < 0.001), polymorph nuclear cells (by 95 +/- 22%, P < 0.01), and in NF-kappaB binding in mononuclear cells by 82 +/- 16% (P < 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-kappaB binding following orange juice, fructose, and water compared with glucose (P < 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 +/- 7% and 77 +/- 8% (P < 0.01), respectively, while fructose or ascorbic acid did not cause any change. CONCLUSIONS: Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.", "title": "Orange juice or fructose intake does not induce oxidative and inflammatory response." }, { "docid": "MED-4985", "text": "Background: Low-fat vegetarian and vegan diets are associated with weight loss, increased insulin sensitivity, and improved cardiovascular health. Objective: We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia, weight, and plasma lipids. Design: Free-living individuals with type 2 diabetes were randomly assigned to a low-fat vegan diet (n = 49) or a diet following 2003 American Diabetes Association guidelines (conventional, n = 50) for 74 wk. Glycated hemoglobin (Hb A1c) and plasma lipids were assessed at weeks 0, 11, 22, 35, 48, 61, and 74. Weight was measured at weeks 0, 22, and 74. Results: Weight loss was significant within each diet group but not significantly different between groups (−4.4 kg in the vegan group and −3.0 kg in the conventional diet group, P = 0.25) and related significantly to Hb A1c changes (r = 0.50, P = 0.001). Hb A1c changes from baseline to 74 wk or last available values were −0.34 and −0.14 for vegan and conventional diets, respectively (P = 0.43). Hb A1c changes from baseline to last available value or last value before any medication adjustment were −0.40 and 0.01 for vegan and conventional diets, respectively (P = 0.03). In analyses before alterations in lipid-lowering medications, total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups, respectively (P = 0.01); LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups, respectively (P = 0.03). Conclusions: Both diets were associated with sustained reductions in weight and plasma lipid concentrations. In an analysis controlling for medication changes, a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations. Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established. This trial was registered at clinicaltrials.gov as NCT00276939.", "title": "A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial" }, { "docid": "MED-2585", "text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.", "title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic." }, { "docid": "MED-2337", "text": "Urticaria, defined by the presence of wheals and/or angio-edema, is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for pae-diatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.", "title": "Management of childhood urticaria: current knowledge and practical recommendations." }, { "docid": "MED-2510", "text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.", "title": "Comparative and meta-analytic insights into life extension via dietary restriction." }, { "docid": "MED-4515", "text": "BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.", "title": "The effect of a plant-based low-carbohydrate (\"Eco-Atkins\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects." }, { "docid": "MED-5242", "text": "PURPOSE: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. MATERIALS AND METHODS: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. RESULTS: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. CONCLUSIONS: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "title": "Caffeine intake and its association with urinary incontinence in United States men: results from National Health and Nutrition Examination Surveys ..." }, { "docid": "MED-2679", "text": "Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.", "title": "Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice." }, { "docid": "MED-3478", "text": "Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance. Copyright Â© 2011 Elsevier Ltd. All rights reserved.", "title": "Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line--a comparative study." }, { "docid": "MED-4625", "text": "Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose. (c) 2010 Elsevier Ltd. All rights reserved.", "title": "Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women." }, { "docid": "MED-4506", "text": "PURPOSE: Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance. However, it is presently unknown whether it may enhance performance during simulated competition. The present study investigated the effects of acute dietary nitrate supplementation on power output (PO), VO2, and performance during 4- and 16.1-km cycling time trials (TT). METHODS: After familiarization, nine club-level competitive male cyclists were assigned in a randomized, crossover design to consume 0.5 L of beetroot juice (BR; containing ∼ 6.2 mmol of nitrate) or 0.5 L of nitrate-depleted BR (placebo, PL; containing ∼ 0.0047 mmol of nitrate), ∼ 2.5 h before the completion of a 4- and a 16.1-km TT. RESULTS: BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P < 0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P > 0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P < 0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P < 0.01). Consequently, BR improved 4-km performance by 2.8% (PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min, P < 0.05) and 16.1-km performance by 2.7% (PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min, P < 0.01). CONCLUSIONS: These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy, as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance.", "title": "Acute dietary nitrate supplementation improves cycling time trial performance." }, { "docid": "MED-5171", "text": "The objective of this study was to determine the prevalence of enterohemorrhagic Escherichia coli (EHEC), E. coli O157, Salmonella, and Listeria monocytogenes in retail food samples from Seattle, Wash. A total of 2,050 samples of ground beef (1,750 samples), mushrooms (100 samples), and sprouts (200 samples) were collected over a 12-month period and analyzed for the presence of these pathogens. PCR assays, followed by culture confirmation were used to determine the presence or absence of each organism. Of the 1,750 ground beef samples analyzed, 61 (3.5%) were positive for EHEC, and 20 (1.1%) of these were positive for E. coli O157. Salmonella was present in 67 (3.8%) of the 1,750 ground beef samples. Of 512 ground beef samples analyzed, 18 (3.5%) were positive for L. monocytogenes. EHEC was found in 12 (6.0%) of the 200 sprout samples, and 3 (1.5%) of these yielded E. coli O157. Of the 200 total sprout samples, 14 (7.0%) were positive for Salmonella and none were positive for L. monocytogenes. Among the 100 mushroom samples, 4 (4.0%) were positive for EHEC but none of these 4 samples were positive for E. coli O157. Salmonella was detected in 5 (5.0%) of the mushroom samples, and L. monocytogenes was found in 1 (1.0%) of the samples.", "title": "Incidence of enterohemorrhagic Escherichia coli, Escherichia coli O157, Salmonella, and Listeria monocytogenes in retail fresh ground beef, sprouts..." }, { "docid": "MED-744", "text": "This paper presents a new interpretation of a unique Bronze Age (c. 3000-1100 BCE) Aegean wall painting in the building of Xeste 3 at Akrotiri,Thera. Crocus carturightianus and its active principle, saffron, are the primary subjects at Xeste 3. Several lines of evidence suggest that the meaning of these frescoes concerns saffron and healing: (1) the unusual degree of visual attention given to the crocus, including the variety of methods for display of the stigmas; (2) the painted depiction of the line of saffron production from plucking blooms to the collection of stigmas; and (3) the sheer number (ninety) of medical indications for which saffron has been used from the Bronze Age to the present. The Xeste 3 frescoes appear to portray a divinity of healing associated with her phytotherapy, saffron. Cultural and commercial interconnections between the Therans, the Aegean world, and their neighboring civilizations in the early 2nd millennium BCE indicate a close network of thematic exchange, but there is no evidence that Akrotiri borrowed any of these medicinal (or iconographic) representations. The complex production line, the monumental illustration of a goddess of medicine with her saffron attribute, and this earliest botanically accurate image of an herbal medication are all Theran innovations.", "title": "Therapy with saffron and the goddess at Thera." }, { "docid": "MED-5040", "text": "BACKGROUND: Studies suggest cardioprotective benefits of dark chocolate containing cocoa. OBJECTIVE: This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. DESIGN: Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). RESULTS: Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P < 0.001; sugar-free and sugared cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P < 0.001). Blood pressure decreased after the ingestion of dark chocolate and sugar-free cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P < 0.001; and diastolic, -1.4 +/- 3.9 mm Hg compared with 2.7 +/- 6.4 mm Hg; P = 0.01; sugar-free cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P < 0.001; and diastolic: -1.2 +/- 8.7 mm Hg compared with 2.8 +/- 5.6 mm Hg; P = 0.014). Endothelial function improved significantly more with sugar-free than with regular cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P < 0.001). CONCLUSIONS: The acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.", "title": "Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial." }, { "docid": "MED-4826", "text": "A role of diet and nutrition in pancreatic carcinogenesis has been suggested, but the association between selected macronutrients, fatty acids, cholesterol and pancreatic cancer remains controversial. We analysed data from a hospital-based case-control study conducted in Italy between 1991 and 2008, including 326 cases (174 men and 152 women) with incident pancreatic cancer, and 652 controls (348 men and 304 women) frequency-matched to cases by sex, age and study centre. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression models conditioned on age, sex and study centre, and adjusted for year of interview, education, tobacco smoking, history of diabetes and energy intake. A positive association was found for animal proteins (OR=1.85 for the highest versus the lowest quintile of intake; 95% CI: 1.15-2.96; p for trend=0.039), whereas a negative association was observed for sugars (OR=0.52; 95% CI: 0.31-0.86; p for trend=0.003). Non-significant negative associations emerged for vegetable proteins (OR=0.69) and polyunsaturated fatty acids (OR=0.67). In conclusion, a diet poor in animal proteins and rich in sugars (mainly derived from fruit) appears to have a beneficial effect on pancreatic cancer risk. Copyright (c) 2009 Elsevier Ltd. All rights reserved.", "title": "Macronutrients, fatty acids, cholesterol and pancreatic cancer." }, { "docid": "MED-3753", "text": "BACKGROUND: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting. PURPOSE: To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials. DATA SOURCES: 4 English-language general and internal medicine journals with high impact factors. STUDY SELECTION: 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009. DATA EXTRACTION: Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus. DATA SYNTHESIS: Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002). LIMITATION: Journals with high impact factors may not be representative. CONCLUSION: Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.", "title": "What's in placebos: who knows? Analysis of randomized, controlled trials." }, { "docid": "MED-2159", "text": "AIMS: Coffee consumption has been recently linked with decreased blood gamma-glutamyltransferase (GGT) activities and protection from alcoholic liver disease. To explore the relationship and dose response, we assessed the impacts of coffee and alcohol intake on serum GGT activity in apparently healthy men and women with varying levels of coffee and alcohol consumption. METHODS: Data on coffee, alcohol consumption and serum GGT activities were collected from 18,899 individuals (8807 men and 10,092 women), mean age 48 years, range 25-74 years, who participated in a large national cross-sectional health survey. Body mass index, smoking index and age were used as covariates in all analyses. RESULTS: Among the study population, 89.8% reported varying levels of coffee consumption; 6.9% were abstainers from alcohol, 86.1% moderate drinkers, 3.7% heavy drinkers and 3.3% former drinkers. In men, the elevation of GGT induced by heavy drinking (>280 g/week) was found to be significantly reduced by coffee consumption exceeding 4 cups per day. A similar trend was also observed among women, which however, did not reach statistical significance. CONCLUSION: Coffee modulates the effect of ethanol on serum GGT activities in a dose- and gender-dependent manner. These observations should be implicated in studies on the possible hepatoprotective effects of coffee in alcohol consumers.", "title": "Dose- and gender-dependent interactions between coffee consumption and serum GGT activity in alcohol consumers." } ]
287	Converting apoE4 to apoE3 by gene editing worsens the pathology associated with apoE4 in human iPSCderived neurons.	[ { "docid": "4709641", "text": "Efforts to develop drugs for Alzheimer's disease (AD) have shown promise in animal studies, only to fail in human trials, suggesting a pressing need to study AD in human model systems. Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration. ApoE4 increased Aβ production in human, but not in mouse, neurons. Converting ApoE4 to ApoE3 by gene editing rescued these phenotypes, indicating the specific effects of ApoE4. Neurons that lacked APOE behaved similarly to those expressing ApoE3, and the introduction of ApoE4 expression recapitulated the pathological phenotypes, suggesting a gain of toxic effects from ApoE4. Treatment of ApoE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of ApoE4 is a viable therapeutic approach for ApoE4-related AD.", "title": "Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector" } ]	[ { "docid": "15347087", "text": "The amyloid cascade hypothesis posits that deposition of the amyloid β (Aβ) peptide in the brain is a key event in the initiation of Alzheimer's disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of Aβ is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of Aβ₁₋₄₂ and extracellular Aβ deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease.", "title": "Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats" }, { "docid": "13717103", "text": "INTRODUCTION Mutations in the FUS gene have been shown to be a rare cause of amyotrophic lateral sclerosis (ALS-FUS) and whilst well documented clinically and genetically there have been relatively few neuropathological studies. Recent work suggested a possible correlation between pathological features such as frequency of basophilic inclusions in neurons and rate of clinical decline, other studies have revealed a discrepancy between the upper motor neuron features detected clinically and the associated pathology. The purpose of this study was to describe the pathological features associated with more recently discovered FUS mutations and reinvestigate those with well recognised mutations in an attempt to correlate the pathology with mutation and/or clinical phenotype. The brains and spinal cords of seven cases of ALS-FUS were examined neuropathologically, including cases with the newly described p. K510E mutation and a case with both a known p. P525L mutation in the FUS gene and a truncating p. Y374X mutation in the TARDBP gene. RESULTS The neuropathology in all cases revealed basophilic and FUS inclusions in the cord. The density and type of inclusions varied markedly between cases, but did not allow a clear correlation with clinical progression. Only one case showed significant motor cortical pathology despite the upper motor neuron clinical features being evident in 4 patients. The case with both a FUS and TARDBP mutation revealed FUS positive inclusions but no TDP-43 pathology. Instead there were unusual p62 positive, FUS negative neuronal and glial inclusions as well as dot-like neurites. CONCLUSIONS The study confirms cases of ALS-FUS to be mainly a lower motor neuron disease and to have pathology that does not appear to neatly correlate with clinical features or genetics. Furthermore, the case with both a FUS and TARDBP mutation reveals an intriguing pathological profile which at least in part involves a very unusual staining pattern for the ubiquitin-binding protein p62.", "title": "ALS-FUS pathology revisited: singleton FUS mutations and an unusual case with both a FUS and TARDBP mutation" }, { "docid": "5953485", "text": "Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs. In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction. Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms. ADAR1 differentiates its functions in RNA editing and RNAi by the formation of either ADAR1/ADAR1 homodimer or Dicer/ADAR1 heterodimer complexes, respectively. As expected, the expression of miRNAs is globally inhibited in ADAR1(-/-) mouse embryos, which, in turn, alters the expression of their target genes and might contribute to their embryonic lethal phenotype.", "title": "ADAR1 Forms a Complex with Dicer to Promote MicroRNA Processing and RNA-Induced Gene Silencing" }, { "docid": "4405194", "text": "Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells. Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.", "title": "Induction of human neuronal cells by defined transcription factors" }, { "docid": "4303075", "text": "Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.", "title": "Direct conversion of fibroblasts to functional neurons by defined factors" }, { "docid": "461550", "text": "Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.", "title": "Multiplex genome engineering using CRISPR/Cas systems." }, { "docid": "4679264", "text": "The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5′ CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts—defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)—were included. A robust and progressive rise in DNA methylation levels across the lifespan was observed for 8/50 loci (GABRA2, GAD1, HOXA1, NEUROD1, NEUROD2, PGR, STK11, SYK) typically in conjunction with declining levels of the corresponding mRNAs. Another 16 loci were defined by a sharp rise in DNA methylation levels within the first few months or years after birth. Disease-associated changes were limited to 2/50 loci in the Alzheimer's cohort, which appeared to reflect an acceleration of the age-related change in normal brain. Additionally, methylation studies on sorted nuclei provided evidence for bidirectional methylation events in cortical neurons during the transition from childhood to advanced age, as reflected by significant increases at 3, and a decrease at 1 of 10 loci. Furthermore, the DNMT3a de novo DNA methyl-transferase was expressed across all ages, including a subset of neurons residing in layers III and V of the mature cortex. Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase.", "title": "DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons" }, { "docid": "4459491", "text": "Alzheimer’s disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer’s disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer’s disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer’s disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer’s disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer’s disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.", "title": "A three-dimensional human neural cell culture model of Alzheimer’s disease" }, { "docid": "6397191", "text": "Endothelin-1 (ET-1) is the predominant endothelin isopeptide generated by the vascular wall and therefore appears to be the most important peptide involved in regulation of cardiovascular events. Many pathologic conditions are associated with elevations of ET-1 in the blood vessel wall. Because these conditions are often cytokine driven, we examined the effects of a mixture of cytokines on ET-1 production in human vascular smooth muscle cells (VSMCs) derived from internal mammary artery and saphenous vein (SV). Incubation of IMA and SV VSMCs with tumor necrosis factor-alpha (10 ng/ml) and interferon-gamma (1000 U/ml) in combination for up to 48 h markedly elevated the expression of mRNA for prepro-ET-1 and the release of ET-1 into the culture medium. This cytokine-stimulated release of ET-1 was inhibited by a series of dual endothelin-converting enzyme (ECE)/neutral endopeptidase inhibitors, phosphoramidon, CGS 26303, and CGS 26393, with an accompanying increase in big ET-1 release but with no effect on expression of mRNA for prepro-ET-1. These same compounds were 10 times more potent at inhibiting the conversion of exogenously applied big ET-1 to ET-1. ECE-1b/c mRNA is present in SV VSMCs, however no ECE-1a is present in these cells. Thus VSMCs most probably contain, like endothelial cells, an intracellular ECE responsible for the endogenous synthesis of ET-1. Under the influence of pro-inflammatory mediators the vascular smooth muscle can therefore become an important site of ET-1 production, as has already been established for the dilator mediators nitric oxide, prostaglandin I2, and prostaglandin E2.", "title": "Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme." }, { "docid": "4347374", "text": "Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes. When produced in the presence of APOBEC3G, vif-defective virus is non-infectious. APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA. APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.", "title": "Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts" }, { "docid": "9217800", "text": "The fatal adult motor neuron disease amyotrophic lateral sclerosis (ALS) shares some clinical and pathological overlap with frontotemporal dementia (FTD), an early-onset neurodegenerative disorder. The RNA/DNA-binding proteins fused in sarcoma (FUS; also known as TLS) and TAR DNA binding protein-43 (TDP-43) have recently been shown to be genetically and pathologically associated with familial forms of ALS and FTD. It is currently unknown whether perturbation of these proteins results in disease through mechanisms that are independent of normal protein function or via the pathophysiological disruption of molecular processes in which they are both critical. Here, we report that Drosophila mutants in which the homolog of FUS is disrupted exhibit decreased adult viability, diminished locomotor speed, and reduced life span compared with controls. These phenotypes were fully rescued by wild-type human FUS, but not ALS-associated mutant FUS proteins. A mutant of the Drosophila homolog of TDP-43 had similar, but more severe, deficits. Through cross-rescue analysis, we demonstrated that FUS acted together with and downstream of TDP-43 in a common genetic pathway in neurons. Furthermore, we found that these proteins associated with each other in an RNA-dependent complex. Our results establish that FUS and TDP-43 function together in vivo and suggest that molecular pathways requiring the combined activities of both of these proteins may be disrupted in ALS and FTD.", "title": "The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila locomotion and life span." }, { "docid": "47018050", "text": "Here, we report that genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.", "title": "CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response" }, { "docid": "7029990", "text": "One type of RNA editing involves the conversion of adenosine residues into inosine in double-stranded RNA through the action of adenosine deaminases acting on RNA (ADAR). A-to-I RNA editing of the coding sequence could result in synthesis of proteins not directly encoded in the genome. ADAR edits also non-coding sequences of target RNAs, such as introns and 3'-untranslated regions, which may affect splicing, translation, and mRNA stability. Three mammalian ADAR gene family members (ADAR1-3) have been identified. Here we investigated phenotypes of mice homozygous for ADAR1 null mutation. Although live ADAR1-/- embryos with normal gross appearance could be recovered up to E11.5, widespread apoptosis was detected in many tissues. Fibroblasts derived from ADAR1-/- embryos were also prone to apoptosis induced by serum deprivation. Our results demonstrate an essential requirement for ADAR1 in embryogenesis and suggest that it functions to promote survival of numerous tissues by editing one or more double-stranded RNAs required for protection against stress-induced apoptosis.", "title": "Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene." }, { "docid": "4462919", "text": "The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that use the highly versatile adeno-associated virus (AAV) delivery vehicle. Here, we characterize six smaller Cas9 orthologues and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being more than 1 kilobase shorter. We packaged SaCas9 and its single guide RNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection, we observed >40% gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol levels. We further assess the genome-wide targeting specificity of SaCas9 and SpCas9 using BLESS, and demonstrate that SaCas9-mediated in vivo genome editing has the potential to be efficient and specific.", "title": "In vivo genome editing using Staphylococcus aureus Cas9" }, { "docid": "29107180", "text": "The structure of the human gene encoding the double-stranded RNA (dsRNA) adenosine deaminase (DRADA) was characterized. This nuclear localized enzyme is involved in the RNA editing required for the expression of certain subtypes of glutamate-gated ion channel subunits. The DRADA gene span 30 kb pairs and harbors 15 exons. The transcription of the DRADA gene driven by the putative promoter region, which contains no typical TATA or CCAAT box-like sequences, is initiated at multiple sites, 164 to 216 nucleotides upstream of the translation initiation codon. The three dsRNA binding motifs (DRBM), 70 amino acid residues long, are each encoded by two exons plus an intervening sequence that interrupts the motif at the identical amino acid position. This finding is consistent with the notion that the dsRNA binding domains may be composed of two separate functional subdomains. Fluorescent in situ hybridization localized the DRADA gene on the long arm chromosome 1, region q21. The gene structure and sequence information reported in this study will facilitate the investigation of involvement of DRADA in hereditary diseases that may be the result of malfunction of glutamate-gated ion channels.", "title": "Genomic organization and chromosomal location of the human dsRNA adenosine deaminase gene: the enzyme for glutamate-activated ion channel RNA editing." }, { "docid": "13969173", "text": "Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration, paralysis, and death. Accurate disease modeling, identifying disease mechanisms, and developing therapeutics is urgently needed. We previously reported motor neuron toxicity through postmortem ALS spinal cord-derived astrocytes. However, these cells can only be harvested after death, and their expansion is limited. We now report a rapid, highly reproducible method to convert adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes). Non-cell autonomous toxicity to motor neurons is found following coculture of i-astrocytes from familial ALS patients with mutation in superoxide dismutase or hexanucleotide expansion in C9orf72 (ORF 72 on chromosome 9) the two most frequent causes of ALS. Remarkably, i-astrocytes from sporadic ALS patients are as toxic as those with causative mutations, suggesting a common mechanism. Easy production and expansion of i-astrocytes now enables rapid disease modeling and high-throughput drug screening to alleviate astrocyte-derived toxicity.", "title": "Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS." }, { "docid": "8790729", "text": "BACKGROUND There is a widespread interest in developing renewable sources of islet-replacement tissue for type I diabetes mellitus. Human mesenchymal cells isolated from the Wharton's jelly of the umbilical cord (HUMSCs), which can be easily obtained and processed compared with embryonic and bone marrow stem cells, possess stem cell properties. HUMSCs may be a valuable source for the generation of islets. METHODOLOGY AND PRINCIPAL FINDINGS HUMSCs were induced to transform into islet-like cell clusters in vitro through stepwise culturing in neuron-conditioned medium. To assess the functional stability of the islet-like cell clusters in vivo, these cell clusters were transplanted into the liver of streptozotocin-induced diabetic rats via laparotomy. Glucose tolerance was measured on week 12 after transplantation accompanied with immunohistochemistry and electron microscopy analysis. These islet-like cell clusters were shown to contain human C-peptide and release human insulin in response to physiological glucose levels. Real-time RT-PCR detected the expressions of insulin and other pancreatic beta-cell-related genes (Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2) in these islet-like cell clusters. The hyperglycemia and glucose intolerance in streptozotocin-induced diabetic rats was significantly alleviated after xenotransplantation of islet-like cell clusters, without the use of immunosuppressants. In addition to the existence of islet-like cell clusters in the liver, some special fused liver cells were also found, which characterized by human insulin and nuclei-positive staining and possessing secretory granules. CONCLUSIONS AND SIGNIFICANCE In this study, we successfully differentiate HUMSCs into mature islet-like cell clusters, and these islet-like cell clusters possess insulin-producing ability in vitro and in vivo. HUMSCs in Wharton's Jelly of the umbilical cord seem to be the preferential source of stem cells to convert into insulin-producing cells, because of the large potential donor pool, its rapid availability, no risk of discomfort for the donor, and low risk of rejection.", "title": "Islet-Like Clusters Derived from Mesenchymal Stem Cells in Wharton's Jelly of the Human Umbilical Cord for Transplantation to Control Type 1 Diabetes" }, { "docid": "39545358", "text": "Neuregulin 1 (NRG1) and its receptor ErbB4 are both susceptibility genes of schizophrenia. However, little is known about the underlying mechanisms of their malfunction. Although ErbB4 is enriched in GABAergic interneurons, the role of NRG1 in excitatory synapse formation in these neurons remains poorly understood. We showed that NRG1 increased both the number and size of PSD-95 puncta and the frequency and amplitude of miniature EPSCs (mEPSCs) in GABAergic interneurons, indicating that NRG1 stimulates the formation of new synapses and strengthens existing synapses. In contrast, NRG1 treatment had no effect on either the number or size of excitatory synapses in glutamatergic neurons, suggesting its synaptogenic effect is specific to GABAergic interneurons. Ecto-ErbB4 treatment diminished both the number and size of excitatory synapses, suggesting that endogenous NRG1 may be critical for basal synapse formation. NRG1 could stimulate the stability of PSD-95 in the manner that requires tyrosine kinase activity of ErbB4. Finally, deletion of ErbB4 in parvalbumin-positive interneurons led to reduced frequency and amplitude of mEPSCs, providing in vivo evidence that ErbB4 is important in excitatory synaptogenesis in interneurons. Together, our findings suggested a novel synaptogenic role of NRG1 in excitatory synapse development, possibly via stabilizing PSD-95, and this effect is specific to GABAergic interneurons. In light of the association of the genes of both NRG1 and ErbB4 with schizophrenia and dysfunction of GABAergic system in this disorder, these results provide insight into its potential pathological mechanism.", "title": "Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons." }, { "docid": "40666943", "text": "PURPOSE To perform a systematic review on the epidemiology, the health-related quality of life (HRQoL) and economic burden of binge eating disorder (BED). METHODS A systematic literature search of English-language articles was conducted using Medline, Embase, PsycINFO, PsycARTICLES, Academic Search Complete, CINAHL Plus, Business Source Premier and Cochrane Library. Literature search on epidemiology was limited to studies published between 2009 and 2013. Cost data were inflated and converted to 2012 US$ purchasing power parities. All of the included studies were assessed for quality. RESULTS Forty-nine articles were included. Data on epidemiology were reported in 31, HRQoL burden in 16, and economic burden in 7 studies. Diagnosis of BED was made using 4th Edition of The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in 46 studies. Lifetime prevalence of BED was 1.1-1.9% in the general population (DSM-IV). BED was associated with significant impairment in aspects of HRQoL relating to both physical and mental health; the Short Form 36 Physical and Mental Component Summary mean scores varied between 31.1 to 47.3 and 32.0 to 49.8, respectively. Compared to individuals without eating disorder, BED was related to increased healthcare utilization and costs. Annual direct healthcare costs per BED patient ranged between $2,372 and $3,731. CONCLUSIONS BED is a serious eating disorder that impairs HRQoL and is related to increased healthcare utilization and healthcare costs. The limited literature warrants further research, especially to better understand the long-term HRQoL and economic burden of BED.", "title": "Epidemiology, health-related quality of life and economic burden of binge eating disorder: a systematic literature review" }, { "docid": "24652030", "text": "Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) occurs early and contributes significantly to cognitive decline in Alzheimer’s disease (AD). Proper function and morphology of BFCNs depends on the supply of nerve growth factor (NGF) from the cortex and the hippocampus. A large number of experiments have shown that decreased supply of NGF at the level of BFCN cell bodies leads to loss of neuronal markers and shrinkage, mimicking what is observed in AD. The delivery of sufficient amounts of NGF signal to BFCN cell bodies depends on the effective participation of several factors including sufficient synthesis and release of NGF, adequate synthesis and expression of NGF receptors by BFCNs, normal signaling and retrograde transport of NGF-receptor complex, and finally effective induction of gene expression by NGF. In the past few years it has become clear that decreased amounts of NGF at the level of BFCN cell bodies is largely due to failed retrograde transport rather than decreased synthesis, binding or expression of NGF receptors in the BFCN terminals. We will discuss in vivo evidence supporting decreased retrograde transport of NGF in a mouse model with BFCN degeneration, and will attempt to match these findings with our studies in postmortem human AD brain. We will speculate about the possible mechanisms of failed NGF retrograde transport and its relationship to AD pathology.", "title": "Alzheimer’s disease and NGF signaling" }, { "docid": "36474", "text": "Realizing the full potential of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) requires efficient methods for genetic modification. However, techniques to generate cell type–specific lineage reporters, as well as reliable tools to disrupt, repair or overexpress genes by gene targeting, are inefficient at best and thus are not routinely used. Here we report the highly efficient targeting of three genes in human pluripotent cells using zinc-finger nuclease (ZFN)–mediated genome editing. First, using ZFNs specific for the OCT4 (POU5F1) locus, we generated OCT4-eGFP reporter cells to monitor the pluripotent state of hESCs. Second, we inserted a transgene into the AAVS1 locus to generate a robust drug-inducible overexpression system in hESCs. Finally, we targeted the PITX3 gene, demonstrating that ZFNs can be used to generate reporter cells by targeting non-expressed genes in hESCs and hiPSCs.", "title": "Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases" }, { "docid": "432261", "text": "The generation of gene-edited animals using the CRISPRs/Cas9 system is based on microinjection into zygotes which is inefficient, time consuming and demands high technical skills. We report the optimization of an electroporation method for intact rat zygotes using sgRNAs and Cas9 protein in combination or not with ssODNs (~100 nt). This resulted in high frequency of knockouts, between 15 and 50% of analyzed animals. Importantly, using ssODNs as donor template resulted in precise knock-in mutations in 25-100% of analyzed animals, comparable to microinjection. Electroporation of long ssDNA or dsDNA donors successfully used in microinjection in the past did not allow generation of genome-edited animals despite dsDNA visualization within zygotes. Thus, simultaneous electroporation of a large number of intact rat zygotes is a rapid, simple, and efficient method for the generation of a variety of genome-edited rats.", "title": "Generation of gene-edited rats by delivery of CRISPR/Cas9 protein and donor DNA into intact zygotes using electroporation" }, { "docid": "2015929", "text": "Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, with astrocytes implicated as contributing substantially to motor neuron death in familial (F)ALS. However, the proposed role of astrocytes in the pathology of ALS derives in part from rodent models of FALS based upon dominant mutations within the superoxide dismutase 1 (SOD1) gene, which account for <2% of all ALS cases. Their role in sporadic (S)ALS, which affects >90% of ALS patients, remains to be established. Using astrocytes generated from postmortem tissue from both FALS and SALS patients, we show that astrocytes derived from both patient groups are similarly toxic to motor neurons. We also demonstrate that SOD1 is a viable target for SALS, as its knockdown significantly attenuates astrocyte-mediated toxicity toward motor neurons. Our data highlight astrocytes as a non-cell autonomous component in SALS and provide an in vitro model system to investigate common disease mechanisms and evaluate potential therapies for SALS and FALS.", "title": "Astrocytes from Familial and Sporadic ALS Patients are Toxic to Motor Neurons" }, { "docid": "27602752", "text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.", "title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS." }, { "docid": "16375102", "text": "The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.", "title": "Direct reprogramming of mouse fibroblasts to neural progenitors." }, { "docid": "18104691", "text": "AIM This review explores the molecular, neurological, and behavioural outcomes in animal models of uterine artery ligation. We analyse the relevance of this type of model to the pathological and functional phenotypes that are consistent with cerebral palsy and its developmental comorbidities in humans. METHOD A literature search of the PubMed database was conducted for research using the uterine artery ligation model published between 1990 and 2013. From the studies included, any relevant neuroanatomical and behavioural deficits were then summarized from each document and used for further analysis. RESULTS There were 25 papers that met the criteria included for review, and several outcomes were summarized from the results of these papers. Fetuses with growth restriction demonstrated a gradient of reduced body weight with a relative sparing of brain mass. There was a significant reduction in the size of the somatosensory cortex, hippocampus, and corpus callosum. The motor cortex appeared to be spared of identifiable deficits. Apoptotic proteins were upregulated, while those important to neuronal survival, growth, and differentiation were downregulated. Neuronal apoptosis and astrogliosis occurred diffusely throughout the brain regions. White matter injury involved oligodendrocyte precursor maturation arrest, hypomyelination, and an aberrant organization of existing myelin. Animals with growth restriction demonstrated deficits in gait, memory, object recognition, and spatial processing. INTERPRETATION This review concludes that neuronal death, white matter injury, motor abnormalities, and cognitive deficits are important outcomes of uterine artery ligation in animal models. Therefore, this is a clinically relevant type of model, as these findings resemble deficits in human cerebral palsy.", "title": "Neurological outcomes of animal models of uterine artery ligation and relevance to human intrauterine growth restriction: a systematic review" }, { "docid": "6153754", "text": "In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury. The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects include early hemorrhagic necrosis leading to major infarction at the injury site. These posttraumatic vascular effects can be treated. Systemic normotension can be restored with volume expansion or vasopressors, and spinal cord blood flow can be improved with dopamine, steroids, nimodipine, or volume expansion. The combination of nimodipine and volume expansion improves posttraumatic spinal cord blood flow and spinal cord function measured by evoked potentials. These results provide strong evidence that posttraumatic ischemia is an important secondary mechanism of injury, and that it can be counteracted.", "title": "Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms." }, { "docid": "4399268", "text": "Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Although patient fibroblasts have been used extensively to study spinal muscular atrophy, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child’s unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.", "title": "Induced pluripotent stem cells from a spinal muscular atrophy patient" }, { "docid": "13293033", "text": "Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of induced pluripotent stem cells (iPSCs) to model DS phenotypes, as a prototypical complex human disease, we generated bona fide DS and wild-type (WT) nonviral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency and had remarkably similar lineage potency, differentiation kinetics, proliferation, and axon extension at early time points. However, at later time points DS cultures showed a twofold bias toward glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress-induced apoptosis, and this could be prevented by the antioxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy 21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Nonviral DS iPSCs can therefore model features of complex human disease in vitro and provide a renewable and ethically unencumbered discovery platform.", "title": "Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology." }, { "docid": "21323758", "text": "Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.", "title": "Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area" } ]
8118	Selling put and call Loss Scenario Examples	[ { "docid": "63363", "text": "See how you can only make the premium amount but your risk is the same as holding the stock when writing a put option.", "title": "" }, { "docid": "388754", "text": "\"The question you are asking concerns the exercise of a short option position. The other replies do not appear to address this situation. Suppose that Apple is trading at $96 and you sell a put option with a strike price of $95 for some future delivery date - say August 2016. The option contract is for 100 shares and you sell the contract for a premium of $3.20. When you sell the option your account will be credited with the premium and debited with the broker commission. The premium you receive will be $320 = 100 x $3.20. The commission you pay will depend on you broker. Now suppose that the price of Apple drops to $90 and your option is exercised, either on expiry or prior to expiry. Then you would be obliged to take delivery of 100 Apple shares at the contracted option strike price of $95 costing you $9,500 plus broker commission. If you immediately sell the Apple shares you have purchased under your contract obligations, then assuming you sell the shares at the current market price of $90 you would realise a loss of $500 ( = 100x($95-$90) )plus commission. Since you received a premium of $320 when you sold the put option, your net loss would be $500-$320 = $180 plus any commissions paid to your broker. Now let's look at the case of selling a call option. Again assume that the price of Apple is $96 and you sell a call option for 100 shares with a strike price of $97 for a premium of $3.60. The premium you receive would be $360 = 100 x $3.60. You would also be debited for commission by your broker. Now suppose that the price of Apple shares rises to $101 and your option is exercised. Then you would be obliged to deliver 100 Apple shares to the party exercising the option at the contracted strike price of $97. If you did not own the shares to effect delivery, then you would need to purchase those shares in the market at the current market price of $101, and then sell them to the party exercising the option at the strike price of $97. This would realise an immediate loss of $400 = 100 x ($101-$97) plus any commission payable. If you did own the shares, then you would simply deliver them and possibly pay some commission or a delivery fee to your broker. Since you received $360 when you sold the option, your net loss would be $40 = $400-$360 plus any commission and fees payable to the broker. It is important to understand that in addition to these accounting items, short option positions carry with them a \"\"margin\"\" requirement. You will need to maintain a margin deposit to show \"\"good faith\"\" so long as the short option position is open. If the option you have sold moves against you, then you will be called upon to put up extra margin to cover any potential losses.\"", "title": "" }, { "docid": "182272", "text": "Here's a simple example for a put, from both sides. Assume XYZ stock trades at $200 right now. Let's say John writes a $190 out of the money put on XYZ stock and sells this put to Abby for the premium, which is say $5. Assume the strike date, or date of settlement, is 6 months from now. Thus Abby is long one put option and John is short one put option (the writer of the option is short the option). On settlement date, let's assume two different scenarios: (1) If the price of the stock decreases by $50, then the put that Abby bought is 'in the money'. Abby's profit can be calculated as being strike price 190 - current stock price 150 - premium paid 5 = $35 So not including any transaction fees, that is a $35 dollar return on a $5 investment. (2) If the price of the stock increases by $50, then the put that Abby bought is worthless and her loss was 100%, or her entire $5 premium. For John, he made $5 in 6 months (in reality you need collateral and good credit to be able to write sizable option positions).", "title": "" } ]	[ { "docid": "440458", "text": "1) Yes, both of your scenarios would lead to earning $10 on the transaction, at the strike date. If you purchased both of them (call it Scenario 3), you would make $20. 2) As to why this transaction may not be possible, consider the following: The Call and Put pricing you describe may not be available. What you have actually created is called 'arbitrage' - 2 identical assets can be bought and sold at different prices, leading to a zero-risk gain for the investor. In the real marketplace, if an option to buy asset X in January cost $90, would an option to sell asset X in January provide $110? Without adding additional complexity about the features of asset x or the features of the options, buying a Call option is the same as selling a Put option [well, when selling a Put option you don't have the ability to choose whether the option is exercised, meaning buying options has value that selling options does not, but ignore that for a moment]. That means that you have arranged a marketplace where you would buy a Call option for only $90, but the seller of that same option would somehow receive $110. For added clarity, consider the following: What if, in your example, the future price ended up being $200? Then, you could exercise your call option, buying a share for $90, selling it for $200, making $110 profit. You would not exercise your put option, making your total profit $110. Now consider: What if, in your example, the future price ended up being $10? You would buy for $10, exercise your put option and sell for $110, making a profit of $100. You would not exercise your call option, making your total profit $100. This highlights that if your initial assumptions existed, you would earn money (at least $20, and at most, unlimited based on a skyrocketing price compared to your $90 put option) regardless of the future price. Therefore such a scenario would not exist in the initial pricing of the options. Now perhaps there is an initial fee involved with the options, where the buyer or seller pays extra money up-front, regardless of the future price. That is a different scenario, and gets into the actual nature of options, where investors will arrange multiple simultaneous transactions in order to limit risk and retain reward within a certain band of future prices. As pointed out by @Nick R, this fee would be very significant, for a call option which had a price set below the current price. Typically, options are sold 'out of the money' initially, which means that at the current share price (at the time the option is purchased), executing the option would lose you money. If you purchase an 'in the money' option, the transaction cost initially would by higher than any apparent gain you might have by immediately executing the option. For a more realistic Options example, assume that it costs $15 initially to buy either the Call option, or the Put option. In that case, after buying both options as listed in your scenarios you would earn a profit if the share price exceeded $120 [The $120 sale price less the $90 call option = $30, which is your total fee initially], or dropped below $80 [The $110 Put price less the $80 purchase price = $30]. This type of transaction implies that you expect the price to either swing up, or swing down, but not fall within the band between $80-$120. Perhaps you might do this if there was an upcoming election or other known event, which might be a failure or success, and you think the market has not properly accounted for either scenario in advance. I will leave further discussion on that topic [arranging options of different prices to create specific bands of profitability / loss] to another answer (or other questions which likely already exist on this site, or in fact, other resources), because it gets more complicated after that point, and is outside the root of your question.", "title": "" }, { "docid": "573077", "text": "\"Being \"\"Long\"\" something means you own it. Being \"\"Short\"\" something means you have created an obligation that you have sold to someone else. If I am long 100 shares of MSFT, that means that I possess 100 shares of MSFT. If I am short 100 shares of MSFT, that means that my broker let me borrow 100 shares of MSFT, and I chose to sell them. While I am short 100 shares of MSFT, I owe 100 shares of MSFT to my broker whenever he demands them back. Until he demands them back, I owe interest on the value of those 100 shares. You short a stock when you feel it is about to drop in price. The idea there is that if MSFT is at $50 and I short it, I borrow 100 shares from my broker and sell for $5000. If MSFT falls to $48 the next day, I buy back the 100 shares and give them back to my broker. I pocket the difference ($50 - $48 = $2/share x 100 shares = $200), minus interest owed. Call and Put options. People manage the risk of owning a stock or speculate on the future move of a stock by buying and selling calls and puts. Call and Put options have 3 important components. The stock symbol they are actionable against (MSFT in this case), the \"\"strike price\"\" - $52 in this case, and an expiration, June. If you buy a MSFT June $52 Call, you are buying the right to purchase MSFT stock before June options expiration (3rd Saturday of the month). They are priced per share (let's say this one cost $0.10/share), and sold in 100 share blocks called a \"\"contract\"\". If you buy 1 MSFT June $52 call in this scenario, it would cost you 100 shares x $0.10/share = $10. If you own this call and the stock spikes to $56 before June, you may exercise your right to purchase this stock (for $52), then immediately sell the stock (at the current price of $56) for a profit of $4 / share ($400 in this case), minus commissions. This is an overly simplified view of this transaction, as this rarely happens, but I have explained it so you understand the value of the option. Typically the exercise of the option is not used, but the option is sold to another party for an equivalent value. You can also sell a Call. Let's say you own 100 shares of MSFT and you would like to make an extra $0.10 a share because you DON'T think the stock price will be up to $52/share by the end of June. So you go to your online brokerage and sell one contract, and receive the $0.10 premium per share, being $10. If the end of June comes and nobody exercises the option you sold, you get to keep the $10 as pure profit (minus commission)! If they do exercise their option, your broker makes you sell your 100 shares of MSFT to that party for the $52 price. If the stock shot up to $56, you don't get to gain from that price move, as you have already committed to selling it to somebody at the $52 price. Again, this exercise scenario is overly simplified, but you should understand the process. A Put is the opposite of a Call. If you own 100 shares of MSFT, and you fear a fall in price, you may buy a PUT with a strike price at your threshold of pain. You might buy a $48 June MSFT Put because you fear the stock falling before June. If the stock does fall below the $48, you are guaranteed that somebody will buy yours at $48, limiting your loss. You will have paid a premium for this right (maybe $0.52/share for example). If the stock never gets down to $48 at the end of June, your option to sell is then worthless, as who would sell their stock at $48 when the market will pay you more? Owning a Put can be treated like owning insurance on the stock from a loss in stock price. Alternatively, if you think there is no way possible it will get down to $48 before the end of June, you may SELL a $48 MSFT June Put. HOWEVER, if the stock does dip down below $48, somebody will exercise their option and force you to buy their stock for $48. Imagine a scenario that MSFT drops to $30 on some drastically terrible news. While everybody else may buy the stock at $30, you are obligated to buy shares for $48. Not good! When you sold the option, somebody paid you a premium for buying that right from you. Often times you will always keep this premium. Sometimes though, you will have to buy a stock at a steep price compared to market. Now options strategies are combinations of buying and selling calls and puts on the same stock. Example -- I could buy a $52 MSFT June Call, and sell a $55 MSFT June Call. I would pay money for the $52 Call that I am long, and receive money for the $55 Call that I am short. The money I receive from the short $55 Call helps offset the cost of buying the $52 Call. If the stock were to go up, I would enjoy the profit within in $52-$55 range, essentially, maxing out my profit at $3/share - what the long/short call spread cost me. There are dozens of strategies of mixing and matching long and short calls and puts depending on what you expect the stock to do, and what you want to profit or protect yourself from. A derivative is any financial device that is derived from some other factor. Options are one of the most simple types of derivatives. The value of the option is derived from the real stock price. Bingo? That's a derivative. Lotto? That is also a derivative. Power companies buy weather derivatives to hedge their energy requirements. There are people selling derivatives based on the number of sunny days in Omaha. Remember those calls and puts on stock prices? There are people that sell calls and puts based on the number of sunny days in Omaha. Sounds kind of ridiculous -- but now imagine that you are a solar power company that gets \"\"free\"\" electricity from the sun and they sell that to their customers. On cloudy days, the solar power company is still on the hook to provide energy to their customers, but they must buy it from a more expensive source. If they own the \"\"Sunny Days in Omaha\"\" derivative, they can make money for every cloudy day over the annual average, thus, hedging their obligation for providing more expensive electricity on cloudy days. For that derivative to work, somebody in the derivative market puts a price on what he believes the odds are of too many cloudy days happening, and somebody who wants to protect his interests from an over abundance of cloudy days purchases this derivative. The energy company buying this derivative has a known cost for the cost of the derivative and works this into their business model. Knowing that they will be compensated for any excessive cloudy days allows them to stabilize their pricing and reduce their risk. The person selling the derivative profits if the number of sunny days is higher than average. The people selling these types of derivatives study the weather in order to make their offers appropriately. This particular example is a fictitious one (I don't believe there is a derivative called \"\"Sunny days in Omaha\"\"), but the concept is real, and the derivatives are based on anything from sunny days, to BLS unemployment statistics, to the apartment vacancy rate of NYC, to the cost of a gallon of milk in Maine. For every situation, somebody is looking to protect themselves from something, and somebody else believes they can profit from it. Now these examples are highly simplified, many derivatives are highly technical, comprised of multiple indicators as a part of its risk profile, and extremely difficult to explain. These things might sound ridiculous, but if you ran a lemonade stand in Omaha, that sunny days derivative just might be your best friend...\"", "title": "" }, { "docid": "154989", "text": "\"Whether or not you make money here depends on whether you are buying or selling the option when you open your position. You certainly would not make money in the scenario where you are buying options at the open. If fact you would end up loosing quite a lot of money. You do not specify whether you are buying or selling the options, so let's assume that you are buying both the call and the put. We'll look a profitable trade at the bottom of my answer. Buying an in-the-money Call option with a strike price of $90 when the underlying asset price is $150 would cost you a small fraction over $6000 = (100 x $60) since the intrinsic value value of the option is $60. Add to this cost any commission charged by your broker. Buying an out-of-the-money Put option with a strike price of $110 when the underlying asset price is $150 would cost you a \"\"small\"\" premium - lets say a premium of something like $0.50. The option has no intrinsic value, only time value and a volatility value, so the exact cost would depend on the time to expiry and the implied volatility of the underlying asset. Since the strike price is \"\"well out of the money\"\", being about 27% below the underlying asset price, the premium would be small. So, assuming the premium of $0.50, you would pay $50 for the option plus any commission applicable. The cash settlement on expiry, with an underlying settlement price of $100, would be a premium of $10 for each of the two options, so you would receive cash of 100 x ($10 + $10) = $2000, less any commission applicable. However, you have paid $6000 + $50 to purchase the options, so you realise a net loss of $6050 - $2000 = $4050 plus any commissions applicable. Thus, you would make a profit on the put option, but you would realise a very large loss on the call option. On the other hand, if you open your position by selling the call option and buying the put option, then you would make money. For the sale of the call option you would receive about $6000. For the purchase of the put option you would pay about $50. On settlement, you would pay $1000 to buy back the call option and you would receive about $1000 when selling the put option. Thus you net profit would be about ($6000 - $1000) for the call position, and ($1000 - $50) for the put position. The net profit would then total $5950 less an commissions payable.\"", "title": "" }, { "docid": "336541", "text": "\"There is unlimited risk in taking a naked call option position. The only risk in taking a covered call position is that you will be required to sell your shares for less than the going market price. I don't entirely agree with the accepted answer given here. You would not lose the amount you paid to buy the shares. Naked Call Option Suppose take a naked call option position by selling a call option. Since there is no limit on how high the price of the underlying share can go, you can be forced to either buy back the option at a very high price, or, in the case that the option is exercised, you can be force. to buy the underlying shares at a very high price and then sell them to the option holder at a very low price. For example, suppose you sell an Apple call option with a strike price of $100 at a premium of $2.50, and for this you receive a payment of $250. Now, if the price of Apple skyrockets to, say, $1000, then you would either have to buy back the option for about $90,000 = 100 x ($1000-$100), or, if the holder exercised the option, then you would need to buy 100 Apple shares at the market price of $1000 per share, costing you $100,000, and then sell them to the option holder at the strike price of $100 for $10,000 = 100 x $100. In either case, you would show a loss of $90,000 on the share transaction, which would be slightly offset by a $250 credit for the premium you received selling the call. There is no limit on the potential loss since there is no limit on how high the underlying share price can go. Covered Call Option Consider now the case of a covered call option. Since you hold the underlying shares, any loss you make on the option position would be \"\"covered\"\" by the profit you make on the underlying shares. Again, suppose you own 100 Apple shares and sell a call option with a strike price of $100 at a premium of $2.50 to earn a payment of $250. If the price of Apple skyrockets to $1000, then there are again two possible scenarios. One, you buy back the option at a premium of about $900 costing you $90,000. In order to cover this cost you would then sell your 100 Apple shares at the market price of $1000 per share to realise $100,000 = 100 x $1000. On the other hand, if your option is exercised, then you would deliver your 100 Apple shares to the option holder at the contracted strike price of $100 per share, thus receiving just $10,000 = 100 x $100. The only \"\"loss\"\" is that you have had to sell your shares for much less than the market price.\"", "title": "" }, { "docid": "387801", "text": "In the scenario you describe, and really, in any scenario, by the nature of how option contracts work: a higher strike put will necessarily be more expensive than the lower strike put (everything else being equal). the lower strike call will necessarily be more expensive than the higher strike call (everything else being equal). In put options, the buyer has the right to sell stock for the strike price. So the higher the strike price, the more money the buyer of the put option can make by selling the shares of stock at a higher price. In call options, it's the exact opposite: buyers of the call option have the right to buy stock at the strike price. The lower the strike price, the better for the buyer: they have the right to buy stock for a lower amount of money. So it must be worth more.", "title": "" }, { "docid": "215118", "text": "\"Bull means the investor is betting on a rising market. Puts are a type of stock option where the seller of a put option promises to buy 100 shares of stock from the buyer of the put option at a pre-agreed price called the strike price on any day before expiration day. The buyer of the put option does not have to sell (it is optional, thats why it is called buying an option). However, the seller of the put is required to make good on their promise to the buyer. The broker can require the seller of the put option to have a deposit, called margin, to help make sure that they can make good on the promise. Profit... The buyer can profit from the put option if the stock price moves down substantially. The buyer of the put option does not need to own the stock, he can sell the option to someone else. If the buyer of the put option also owns the stock, the put option can be thought of like an insurance policy on the value of the stock. The seller of the put option profits if the stock price stays the same or rises. Basically, the seller comes out best if they can sell put options that no one ends up using by expiration day. A spread is an investment consisting of buying one option and selling another. Let's put bull and put and spread together with an example from Apple. So, if you believed Apple Inc. AAPL (currently 595.32) was going up or staying the same through JAN you could sell the 600 JAN put and buy the 550 put. If the price rises beyond 600, your profit would be the difference in price of the puts. Let's explore this a little deeper (prices from google finance 31 Oct 2012): Worst Case: AAPL drops below 550. The bull put spread investor owes (600-550)x100 shares = $5000 in JAN but received $2,035 for taking this risk. EDIT 2016: The \"\"worst case\"\" was the outcome in this example, the AAPL stock price on options expiry Jan 18, 2013 was about $500/share. Net profit = $2,035 - $5,000 = -$2965 = LOSS of $2965 Best Case: AAPL stays above 600 on expiration day in JAN. Net Profit = $2,035 - 0 = $2035 Break Even: If AAPL drops to 579.65, the value of the 600 JAN AAPL put sold will equal the $2,035 collected and the bull put spread investor will break even. Commissions have been ignored in this example.\"", "title": "" }, { "docid": "234935", "text": "I guess the opposite of being hedged is being unhedged. Typically, a hedge is an additional position that you would take on in order to mitigate the potential for losses on another position. I'll give an example: Say that I purchase 100 shares of stock XYZ at $10 per share because I believe its price will increase in the future. At that point, my full investment of $1000 is at risk, so the position is not hedged. If the price of XYZ decreases to $8, then I've lost $200. If the price of XYZ increases to $12, then I've gained $200; the profit/loss curve has a linear relationship to the future stock price. Suppose that I decide to hedge my XYZ position by purchasing a put option. I purchase a single option contract (corresponding to my 100 shares) with a strike price of $10 and an expiration date in January 2013 for a price of $0.50/share. This means that until the contract expires, I can always sell my XYZ shares for a minimum of $10. Therefore, if the price of XYZ decreases to $8, then I've only lost $50 (the price of the option contract), compared to the $200 that I would have lost if the position was unhedged. Likewise, however, if the price increases to $12, then I've only gained a net total of $150 due to the money I spent on the hedge. (the details of how much money you would actually lose in the hedged scenario are simplified out above; even out-of-the-money options retain some value before expiration, but pricing of options is outside of the scope of this post) So, as a more pointed answer to your question, I would say that the hedged/unhedged status of a position can be characterized by its potential for loss. If you don't have any other assets that will increase in value to offset losses on your position of interest, I would call it unhedged.", "title": "" }, { "docid": "363043", "text": "\"A covered call risks the disparity between the purchase price and the potential forced or \"\"called\"\" sale price less the premium received. So buy a stock for $10.00 believing it will drop you or not rise above $14.00 for a given period of days. You sell a call for a $1.00 agreeing to sell your stock for $14.00 and your wrong...the stock rises and at 14.00 or above during the option period the person who paid you the $1.00 premium gets the stock for a net effective price of $15.00. You have a gain of 5$. Your hypothecated loss is unlimited in that the stock could go to $1mil a share. That loss is an opportunity loss you still had a modest profit in actual $. The naked call is a different beast. you get the 1.00 in commission to sell a stock you don't own but must pay for that right. so lets say you net .75 in commission per share after your sell the option. as long as the stock trades below $14.00 during the period of the option you sold your golden. It rises above the strike price you must now buy that stock at market to fill the order when the counter party choses to exercise the option which results in a REAL loss of 100% of the stocks market price less the .75 a share you made. in the scenarios a 1000 shares that for up $30.00 a share over the strike price make you $5,000 in a covered call and lose you $29,250 in a naked call.Naked calls are speculative. Covered calls are strategic.\"", "title": "" }, { "docid": "528052", "text": "\"Your question indicates that you might have a little confusion about put options and/or leveraging. There's no sense I'm aware of in which purchasing a put levers a position. Purchasing a put will cost you money up front. Leveraging typically means entering a transaction that gives you extra money now that you can use to buy other things. If you meant to sell a put, that will make money up front but there is no possibility of making money later. Best case scenario the put is not exercised. The other use of the term \"\"leverage\"\" refers to purchasing an asset that, proportionally, goes up faster than the value of the underlying. For example, a call option. If you purchase a put, you are buying downside protection, which is kind of the opposite of leverage. Notice that for an American put you will most likely be better off selling the put when the price of the underlying falls than exercising it. That way you make the money you would have made by exercising plus whatever optional value the put still contains. That is true unless the time value of money is greater than the optional (insurance) value. Since the time value of money is currently exceptionally low, this is unlikely. Anyway, if you sell the option instead of exercising, you don't need to own any shares at all. Even if you do exercise, you can just buy them on the market and sell right away so I wouldn't worry about what you happen to be holding. The rules for what you can trade with a cash instead of a margin account vary by broker, I think. You can usually buy puts and calls in a cash account, but more advanced strategies, such as writing options, are prohibited. Ask your broker or check their help pages to see what you have available to you.\"", "title": "" }, { "docid": "581866", "text": "To try to answer the three explicit questions: Every share of stock is treated proportionately: each share is assigned the same dollar amount of investment (1/176th part of the contribution in the example), and has the same discount amount (15% of $20 or $25, depending on when you sell, usually). So if you immediately sell 120 shares at $25, you have taxable income on the gain for those shares (120($25-$17)). Either selling immediately or holding for the long term period (12-18 mo) can be advantageous, just in different ways. Selling immediately avoids a risk of a decline in the price of the stock, and allows you to invest elsewhere and earn income on the proceeds for the next 12-18 months that you would not otherwise have had. The downside is that all of your gain ($25-$17 per share) is taxed as ordinary income. Holding for the full period is advantageous in that only the discount (15% of $20 or $25) will be taxed as ordinary income and the rest of the gain (sell price minus $20 or $25) will be taxed at long-term capital gain tax rates, which generally are lower than ordinary rates (all taxes are due in the year you do sell). The catch is you will sell at different price, higher or lower, and thus have a risk of loss (or gain). You will never be (Federally) double taxed in any scenario. The $3000 you put in will not be taxed after all is sold, as it is a return of your capital investment. All money you receive in excess of the $3000 will be taxed, in all scenarios, just potentially at different rates, ordinary or capital gain. (All this ignores AMT considerations, which you likely are not subject to.)", "title": "" }, { "docid": "195152", "text": "Put options are contracts to sell. You pay me a fee for the right to put the stock (or other underlying security) in my hands if you want to. That happens on a specific date (the strike date) and a specified price (the strike price). You can decide not to exercise that right, but I must follow through and let you sell it to me if you want to. Put options can be used by the purchaser to cap losses. For example: You purchase a PUT option for GE Oct19 13.00 from me. On October 19th, you can make me let you sell your GE stock to me for $13.00 a share. If the price for GE has fallen to $12.00, that would be a good idea. If its now at $15.00 a share, you will probably keep the GE or sell it at the current market price. Call options are contracts to buy. The same idea only in the other direction: You pay me a fee for the right to call the stock away from me. Calls also have a strike date and strike price. Like a put, you can choose not to exercises it. You can choose to buy the stock from me (on the strike date for the strike price), but I have to let you buy it from me if you want to. For example: You purchase a CALL option for GE Oct19 16.00 option from me. On October 19th, you can buy my GE stock from me for $16.00 a share. If the current price is $17.50, you should make me let you buy if from me for $16.00. If its less than $16.00, you could by it at the current market price for less. Commonly, options are for a block of 100 shares of the underlying security. Note: this is a general description. Options can be very complicated. The fee you pay for the option and the transaction fees associated with the shares affects whether or not exercising is financially beneficial. Options can be VERY RISKY. You can loose all your money as there is no innate value in the option, only how it relates to the underlying security. Before your brokerage will let you trade, there are disclosures you must read and affirm that you understand the risk.", "title": "" }, { "docid": "230666", "text": "There are several ways to protect against (or even profit from) a market correction. Hedge funds do this by hedging, that is, buying a stock that they think is strong and selling short a paired stock that is weak. If you hold, say, a strong retail company in your portfolio, you might sell short an equal weight of a weak retail company. These are like buying insurance on your portfolio. If you own 300 shares of XYZ, currently trading at $68, you buy puts at a level at a strike price that lets you sleep at night. For example, you might buy 3 XYZ 6-month puts with a strike price of $60. A disadvantage is that the puts are wasting assets, that is, their time premium (which you paid for at the outset) becomes zero at expiration. (This is why it is like insurance. You wouldn't complain that your insurance premium was lost when you purchase insurance on your house and the house doesn't burn down, would you? Of course not. The purpose of the insurance is to protect your investment.) Note that as these puts are married, they only protect your portfolio. Instead of profiting from a correction, you would merely protect your portfolio during a correction. (No small feat!) If your portfolio is similar to the market, you can buy S&P index puts. If your market reflects a lot of technology, you can buy technology sector puts. Say you have a portfolio of $80K that reflects the market. You could buy out-of-the-market puts (again reflecting your tolerance for loss). Any losses in your portfolio after the puts go in-the-money would be (more or less) offset by gains in the puts. An advantage is that the bid/ask spread is smaller for the S&P. You would pay less for the protection. Also, the S&P puts are cash settled (meaning you get money put in your account on the business day after expiration day). A disadvantage is that the puts do not linearly go up as the market drops. (Delta hedging is a big deal in and of itself.) Another disadvantage is that they are wasting assets (see the Married puts section, previous). While the S&P puts can be used to maintain your market portfolio in the midst of a correction, you could purchase more puts than needed. If you had correctly timed the market, then your portfolio with puts would increase. (Your mileage may vary; some have predicted an imminent market crash way too often.) Collars involve selling out-of-the-money calls and using the premiums to buy out-of-the-money puts. There are many varieties of collars, but the most straightforward is to sell 1 call and buy 1 put for every 100 shares. (This can also be done for index puts and calls.) This has the effect of simultaneously: You get your insurance for almost free. But again, it is protecting your portfolio. As the name implies, you make money when the market goes bearish. Bear put spreads involve buying puts at a close strike price and selling an equal number of puts at a lower strike price than the first. You have a defined maximum loss (the premium you paid for the higher put minus the premium you received for the lower put). You have a defined maximum gain (the difference between strikes minus the defined maximum loss). Buy S&P 500 index puts. If you buy deep out-of-the-money puts, it won't cost much, but you have little probability of it paying off. But if they go in-the-money, there could be a sizable payoff. This is similar to putting one chip on red 18 on the roulette wheel. But rather than paying off 35:1, it is a variable payoff. If you're $1 in the money, you just get $100. If you're $12 in the money, you have a $1200 payoff. If you buy at-the-money puts, it will cost a lot, and your probability will be about 1 in 2 that you will pay off. In our roulette analogy, this is like putting 30 chips on the Even bet of the roulette wheel. The variable payoff is as in the previous paragraph. But you're more likely to get a payoff. And you will lose it all of the roulette ball lands on an Odd number, 0, or 00. (That is, the underlying of your put goes up or stays the same.) If your research shows you what good stocks to buy, it may also tell you which stocks are ripe for a fall. You could short-sell these stocks or buy puts on them. Similar to short-selling stocks or buying puts, you could sell short overpriced sectors or buy puts on them. There are ETFs that will allow you benefit from falling prices without needing to have a margin agreement or options agreement in place. Sorry to have a lengthy answer. Many other answers emphasize that one shouldn't try to time the market. But that is not the OP's question. Provided here are both:", "title": "" }, { "docid": "272547", "text": "\"Ok, I think what you're really asking is \"\"how can I benefit from a collapse in the price of gold?\"\" :-) And that's easy. (The hard part's making that kind of call with money on the line...) The ETF GLD is entirely physical gold sitting in a bank vault. In New York, I believe. You could simply sell it short. Alternatively, you could buy a put option on it. Even more risky, you could sell a (naked) call option on it. i.e. you receive the option premium up front, and if it expires worthless you keep the money. Of course, if gold goes up, you're on the hook. (Don't do this.) (the \"\"Don't do this\"\" was added by Chris W. Rea. I agree that selling naked options is best avoided, but I'm not going to tell you what to do. What I should have done was make clear that your potential losses are unlimited when selling naked calls. For example, if you sold a single GLD naked call, and gold went to shoot to $1,000,000/oz, you'd be on the hook for around $10,000,000. An unrealistic example, perhaps, but one that's worth pondering to grasp the risk you'd be exposing yourself to with selling naked calls. -- Patches) Alternative ETFs that work the same, holding physical gold, are IAU and SGOL. With those the gold is stored in London and Switzerland, respectively, if I remember right. Gold peaked around $1900 and is now back down to the $1500s. So, is the run over, and it's all downhill from here? Or is it a simple retracement, gathering strength to push past $2000? I have no idea. And I make no recommendations.\"", "title": "" }, { "docid": "254474", "text": "\"I think the question, as worded, has some incorrect assumptions built into it, but let me try to hit the key answers that I think might help: Your broker can't really do anything here. Your broker doesn't own the calls you sold, and can't elect to exercise someone else's calls. Your broker can take action to liquidate positions when you are in margin calls, but the scenario you describe wouldn't generate them: If you are long stock, and short calls, the calls are covered, and have no margin requirement. The stock is the only collateral you need, and you can have the position on in a cash (non-margin) account. So, assuming you haven't bought other things on margin that have gone south and are generating calls, your broker has no right to do anything to you. If you're wondering about the \"\"other guy\"\", meaning the person who is long the calls that you are short, they are the one who can impact you, by exercising their right to buy the stock from you. In that scenario, you make $21, your maximum possible return (since you bought the stock at $100, collected $1 premium, and sold it for $120. But they usually won't do that before expiration, and they pretty definitely won't here. The reason they usually won't is that most options trade above their intrinsic value (the amount that they're in the money). In your example, the options aren't in the money at all. The stock is trading at 120, and the option gives the owner the right to buy at 120. Put another way, exercising the option lets the owner buy the stock for the exact same price anyone with no options can in the market. So, if the call has any value whatsoever, exercising it is irrational; the owner would be better off selling the call and buying the stock in the market.\"", "title": "" }, { "docid": "514841", "text": "A limit order is simply an order to buy at a maximum price or sell at a minimum price. For example, if the price is $100 and you want to sell if the price rises to $110, then you can simply put a limit order to sell at $110. The order will be placed in the market and when the price reaches $110 your order will be executed. If the price gaps at the open to $111, then you would end up selling for $111. In other words you will get a minimum of $110 per share. A stop limit order is where you put a stop loss order, which when it gets triggered, will place a limit order in the market for you. For example, you want to limit your losses by placing a stop loss order if the price drops to $90. If you chose a market order with your stop loss as soon as the price hits $90 your stop loss would be triggered and the shares would sell at the next available price, usually at $90, but could be less if the market gaps down past $90. If on the other hand you placed a limit order at $89.50 with your stop loss, when the stop loss order gets triggered at $90 your limit order will be placed into the market to sell at $89.50. So you would get a minimum of $89.50 per share, however, if the market gaps down below $89.50 your order will be placed onto the market but it won't sell, unless the price goes back to or above $89.50. Hope this helps.", "title": "" }, { "docid": "289073", "text": "\"Buying (or selling) a futures contract means that you are entering into a contractual agreement to buy (or sell) the contracted commodity or financial instrument in the contracted amount (the contract size) at the price you have bought (or sold) the contract on the contract expire date (maturity date). It is important to understand that futures contracts are tradeable instruments, meaning that you are free to sell (or buy back) your contract at any time before the expiry date. For example, if you buy 1 \"\"lot\"\" (1 contract) of a gold future on the Comex exchange for the contract month of December 2016, then you entering into a contract to buy 100 ounces (the contract size) of gold at the price at which you buy the contract - not the spot price on the day of expiry when the contract comes to maturity. The December 2016 gold futures contract has an expiry date of 28 December. You are free to trade this contract at any time before its expiry by selling it back to another market participant. If you sell the contract at a price higher than you have purchased it, then you will realise a profit of 100 times the difference between the price you bought the contract and the price you sold the contract, where 100 is the contract size of the gold contract. Similarly, if you sell the contract at a price lower than the price you have purchased it, then you will realise a loss. (Commissions paid will also effect your net profit or loss). If you hold your contract until the expiry date and exercise your contract by taking (or making) delivery, then you are obliged to buy (or sell) 100 ounces of gold at the price at which you bought (or sold) the contract - not the current spot price. So long as your contract is \"\"open\"\" (i.e., prior to the expiry date and so long as you own the contract) you are required to make a \"\"good faith deposit\"\" to show that you intend to honour your contractual obligations. This deposit is usually called \"\"initial margin\"\". Typically, the initial margin amount will be about 2% of the total contract value for the gold contract. So if you buy (or sell) one contract for 100 ounces of gold at, say, $1275 an ounce, then the total contract value will be $127,500 and your deposit requirement would be about $2,500. The initial margin is returned to you when you sell (or buy) back your futures contract, or when you exercise your contract on expiry. In addition to initial margin, you will be required to maintain a second type of margin called \"\"variation margin\"\". The variation margin is the running profit or loss you are showing on your open contract. For the sake of simplicity, lets look only at the case where you have purchased a futures contract. If the futures price is higher than your contract (buy) price, then you are showing a profit on your current position and this profit (the variation margin) will be used to offset your initial margin requirement. Conversely, if the futures price has dropped below your contracted (buy) price, then you will be showing a loss on your open position and this loss (the variation margin) will be added to your initial margin and you will be called to put up more money in order to show good faith that you intend to honour your obligations. Note that neither the initial margin nor the variation margin are accounting items. In other words, these are not postings that are debited or credited to the ledger in your trading account. So in some sense \"\"you don't have to pay anything upfront\"\", but you do need to put up a refundable deposit to show good faith.\"", "title": "" }, { "docid": "557356", "text": "\"There are two reasons why most options aren't exercised. The first is obvious, and the second, less so. The obvious: An option that's practically worthless doesn't get exercised. Options that reach expiry and remain unexercised are almost always worthless bets that simply didn't pay off. This includes calls with strikes above the current underlying price, and puts with strikes below it. A heck of a lot of options. If an option with value was somehow left to expire, it was probably a mistake, or else the transaction costs outweighed the value remaining; not quite worthless, but not \"\"worth it\"\" either. The less obvious: An option with value can be cancelled any time before expiration. A trader that buys an option may at some point show a gain sooner than anticipated, or a loss in excess of his tolerance. If a gain, he may want to sell before expiry to realize the gain sooner. Similarly, if a loss, he may want to take the loss sooner. In both cases, his capital is freed up and he can take another position. And — this is the key part — the other end matched up with that option sale is often a buyer that had created (written) exactly such an option contract in the first place – the option writer – and who is looking to get out of his position. Option writers are the traders responsible, in the first place, for creating options and increasing the \"\"open interest.\"\" Anybody with the right kind and level of options trading account can do this. A trader that writes an option does so by instructing his broker to \"\"sell to open\"\" a new instance of the option. The trader then has a short position (negative quantity) in that option, and all the while may be subject to the obligations that match the option's exercise rights. The only way for the option writer to get out of that short position and its obligations are these: Not by choice: To get assigned. That is to say: a buyer exercised the option. The writer has to fulfill his obligation by delivering the underlying (if a call) to the option holder, or buying the underlying (if a put) from the option holder. Not by choice: The option expires worthless. This is the ideal scenario for a writer because 100% of the premium received (less transaction costs) is profit. By choice: The writer is free to buy back exactly the same kind of option before expiry using a \"\"buy to close\"\" order with their broker. Once the option has been purchased with a \"\"buy to close\"\", it eliminates the short position and obligation. The option is cancelled. The open interest declines. Options thus cancelled just don't live long enough to either expire or be exercised.\"", "title": "" }, { "docid": "140371", "text": "To expand on the comment made by @NateEldredge, you're looking to take a short position. A short position essentially functions as follows: Here's the rub: you have unlimited loss potential. Maybe you borrow a share and sell it at $10. Maybe in a month you still haven't closed the position and now the share is trading at $1,000. The share lender comes calling for their share and you have to close the position at $1,000 for a loss of $990. Now what if it was $1,000,000 per share, etc. To avoid this unlimited loss risk, you can instead buy a put option contract. In this situation you buy a contract that will expire at some point in the future for the right to sell a share of stock for $x. You get to put that share on to someone else. If the underlying stock price were to instead rise above the put's exercise price, the put will expire worthless — but your loss is limited to the premium paid to acquire the put option contract. There are all sorts of advanced options trades sometimes including taking a short or long position in a security. It's generally not advisable to undertake these sorts of trades until you're very comfortable with the mechanics of the contracts. It's definitely not advisable to take an unhedged short position, either by borrowing someone else's share(s) to sell or selling an option (when you sell the option you take the risk), because of the unlimited loss potential described above.", "title": "" }, { "docid": "310837", "text": "\"I look for buying a call option only at the money, but first understand the background above: Let's suppose X stock is being traded by $10.00 and it's January The call option is being traded by $0.20 with strike $11.00 for February. (I always look for 2% prize or more) I buy 100 stocks by $10.00 each and sell the option, earning $0.20 for each X stock. I will have to deliver my stocks by $11.00 (strike value agreed). No problem for me here, I took the prize plus the gain of $1.00. (continuing from item 3) I still can sell the option for the next month with strike equal or higher than that I bought. For instance, I can sell a call option of strike $10.00 and it might be worth to deliver stocks by $10.00 and take the prize. (continuing from item 3) Probably, it won't be possible to sell a call option with strike at the price that I paid for the stock, but that's not a problem. At the end of the option life (in February), the strike was $11.00 but the stock's price is $8.00. I got the $0.20 as prize and my stocks are free for trade again. I'll sell the call option for March with strike $9.00 (taking around 2% of prize). Well, I don't want to sell my stocks by $9.00 and make loss, right? But I'm selling the call option anyway. Then I wait till the price of the stock gets near the strike value (almost ATM) and I \"\"re-buy\"\" the option sold (Example: [StockX]C9 where C means month = March) and sell again the call option with higher strike to April (Example [StockX]D10, where D means month = April) PS.: At item 9 there should be no loss between the action of \"\"re-buy\"\" and sell to roll-out to the next month. When re-buying it with the stock's price near the strike, option value for March (C9) will be lower than when selling it to April (D10). This isn't any rule to be followed, this is just a conservative (I think they call it hedge) way to handle options and stocks. Few free to make money according to your goals and your style. The perfect rule is the one that meet your expectation, don't take the generalized rules too serious.\"", "title": "" }, { "docid": "279185", "text": "\"Simplest way to answer this is that on margin, one is using borrowed assets and thus there are strings that come with doing that. Thus, if the amount of equity left gets too low, the broker has a legal obligation to close the position which can be selling purchased shares or buying back borrowed shares depending on if this is a long or short position respectively. Investopedia has an example that they walk through as the call is where you are asked to either put in more money to the account or the position may be closed because the broker wants their money back. What is Maintenance Margin? A maintenance margin is the required amount of securities an investor must hold in his account if he either purchases shares on margin, or if he sells shares short. If an investor's margin balance falls below the set maintenance margin, the investor would then need to contribute additional funds to the account or liquidate stocks in the account to bring the account back to the initial margin requirement. This request is known as a margin call. As discussed previously, the Federal Reserve Board sets the initial margin requirement (currently at 50%). The Federal Reserve Board also sets the maintenance margin. The maintenance margin, the amount of equity an investor needs to hold in his account if he buys stock on margin or sells shares short, is 25%. Keep in mind, however, that this 25% level is the minimum level set, brokerage firms can increase, but not decrease this level as they desire. Example: Determining when a margin call would occur. Assume that an investor had purchased 500 shares of Newco's stock. The shares were trading at $50 when the transaction was executed. The initial margin requirement on the account was 70% and the maintenance margin is 30%. Assume no transaction costs. Determine the price at which the investor will receive a margin call. Answer: Calculate the price as follows: $50 (1- 0.70) = $21.43 1 - 0.30 A margin call would be received when the price of Newco's stock fell below $21.43 per share. At that time, the investor would either need to deposit additional funds or liquidate shares to satisfy the initial margin requirement. Most people don't want \"\"Margin Calls\"\" but stocks may move in unexpected ways and this is where there are mechanisms to limit losses, especially for the brokerage firm that wants to make as much money as possible. Cancel what trade? No, the broker will close the position if the requirement isn't kept. Basically think of this as a way for the broker to get their money back if necessary while following federal rules. This would be selling in a long position or buying in a short sale situation. The Margin Investor walks through an example where an e-mail would be sent and if the requirement isn't met then the position gets exited as per the law.\"", "title": "" }, { "docid": "365926", "text": "You can execute block trades on the options market and get exercised for shares to create a very large position in Energy Transfer Partners LP without moving the stock market. You can then place limit sell orders, after selling directly into the market and keep an overhang of low priced shares (the technical analysis traders won't know what you specifically are doing, and will call this 'resistance'). If you hit nice even numbers (multiples of 5, multiples of 10) with your sell orders, you can exacerbate selling as many market participants will have their own stop loss orders at those numbers, causing other people to sell at lower and lower prices automatically, and simultaneously keep your massive ask in effect. If your position is bigger than the demand then you can keep a stock lower. The secondary market doesn't inherently affect a company in any way. But many companies have borrowed against the price of their shares, and if you get the share price low enough they can get suddenly margin called and be unable to service their existing debt. You will also lose a lot of money doing this, so you can also buy puts along the way or attempt to execute a collar to lower your own losses. The collar strategy is nice because it is unlikely that other traders and analysts will notice what you are doing, since there are calls, puts and share orders involved in creating it. One person may notice the block trade for the calls initially, but nobody will notice it is part of a larger strategy with multiple legs. With the share position, you may also be able to vote on some things, but that solely depends on the conditions of the shares.", "title": "" }, { "docid": "318321", "text": "My understanding is that losses are first deductible against any capital gains you may have, then against your regular income (up to $3,000 per year). If you still have a loss after that, the loss may be carried over to offset capital gains or income in subsequent years As you suspect, a short term capital loss is deductible against short term capital gains and long term losses are deductible against long term gains. So taking the loss now MIGHT be beneficial from a tax perspective. I say MIGHT because there are a couple scenarios in which it either may not matter, or actually be detrimental: If you don't have any short term capital gains this year, but you have long term capital gains, you would have to use the short term loss to offset the long term gain before you could apply it to ordinary income. So in that situation you lose out on the difference between the long term tax rate (15%) and your ordinary income rate (potentially higher). If you keep the stock, and sell it for a long term loss next year, but you only have short-term capital gains or no capital gains next year, then you may use the long term loss to offset your short-term gains (first) or your ordinary income. Clear as mud? The whole mess is outlined in IRS Publication 550 Finally, if you still think the stock is good, but just want to take the tax loss, you can sell the stock now (to realize the loss) then re-buy it in 30 days. This is called Tax Loss Harvesting. The 30 day delay is an IRS requirement for being allowed to realize the loss.", "title": "" }, { "docid": "271109", "text": "The put vs call assignment risk, is actually the reverse: in-the-money calls are more likely to be exercised early than puts. Exercising a call locks in profit for the option holder because they can buy the shares at below market price, and immediately sell them at the higher market price. If there are dividends due, the risk is even higher. By contrast, exercising an in-the-money put locks in a loss for the holder, so it's less common.", "title": "" }, { "docid": "502164", "text": "I am very surprised no one mentioned the Stock Repair Option Strategy which has real benefits and is one of the mainstream Option Strategies. Quote: Who Should Consider Using the Stock Repair Strategy? In a nutshell, you are buying call options with current strike price (at-the-money) and sell call options with higher strike price (out-of-the-money), all with the same expiry dates. The only reason to also sell call options here is to recover your premium paid for the other call options. If you are comfortable paying that premium, you just buy the call options without selling the others. In case your stock will rise moderately to a price between the two strike prices, your call option will rise together with your stock, so you will be faster to recover your money. This is the main reason it is called Repair. If you have sold any call options, as the price rises, you have to be careful when it reaches the strike price of the options sold, as from there on you will begin incurring losses. It is however exactly the lucky outcome you were hoping for, your stock is higher, and you can buy back those loss making options - then or shortly before. If you didn't sell any options and payed your premium, you don't need to worry at all at this stage. WARNING It should be noted that the Stock Repair Strategy offers no protection for your stock price further falling down. In that case all those options will expire worthless or you can sell back the ones your bought but likely not for much. In order to have the downside protection for your stock, there are other strategies, the simplest one being buying a Put Option at-the-money or slightly lower. That will effectively cut your possible losses to the Option Premium (which is the main use of that option). Again, if you hate to pay that premium, you can offset it by selling other options that you either hope won't be exercised or take steps to protect you against those.", "title": "" }, { "docid": "69395", "text": "\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"", "title": "" }, { "docid": "122188", "text": "Nolube's brain is in his bowels. green-light is pissed as hell. I hope that guy I told to buy it in investing did so. I suggested he sell half at $5.60 then put a stop loss on the rest at $5.30. That was a very conservative idea, but I didn't know his risk scenario.", "title": "" }, { "docid": "173745", "text": "Let's consider that transaction cost is 0(zero) for calculation. In the scenario you have stated, maximum profit that could be made is 55$, however risk is unlimited. Hedging can also be used to limit your losses, let's consider this scenario. Stock ABC trading @ 100$, I'll buy the stock ABC @ 100$ and buy a put option of ABC @ strike price 90$ for a premium of 5$ with an expiration date of 1 month. Possible outcomes I end up in a loss in 3 out of 4 scenarios, however my loss is limited to 15$, whereas profit is unlimited.", "title": "" }, { "docid": "501504", "text": "What financial instruments are there that are profitable when an underlying assets falls? The instrument you are looking for is called an Option, specifically a Put Option. It allows you, within the validity date, to sell ('Put') the respective shares to the option giver, at the predefined Strike Price. For example, let's assume APPL trades currently at 100 $ per share, and you think they will go down a lot. You buy one Put Option for 100 shares (they always come for larger amounts like 100s) for a Strike Price of 90 $, and pay 5 $ for it (it would be cheap if nobody believes they will fall that much). Note the last sentence under 2. - it is rather easy and very common when trading options to make complete losses. You have been warned. Are they available for IPOs? They could be available for IPOs, even before the IPO. However, someone has to put them out (some large bank, typically), which is some effort, and they would only do that if they expect enough interest and volume in the trade. most of the time, there will be no such options on the market. Are they available for foreign stocks?Yes, but again only selectively - only if the stock is well known and interesting enough for a broad audience.", "title": "" }, { "docid": "490176", "text": "\"Individuals most definitely can have NOL. This is covered in the IRS publication 536. What is the difference between NOL and capital loss? NOL is Net Operating Loss. I.e.: a situation where your (allowable) expenses and deductions exceed your gross income. Basically it means that you have negative income for that year, for tax purposes. Capital loss occurs when the total amount of your capital gains reported on Schedule D is negative. What are their relations then? Not all expenses and deductions that you usually put on your tax return are allowed for NOL calculation. For example, capital loss is not allowed. I.e.: if you earned $2000 and you lost in stocks $3000 - you do not get a $1K NOL. Capital losses are excluded from NOL calculation and in this scenario you still have non-negative income for NOL purposes even though it is offset in full by capital loss deduction and your \"\"taxable income\"\" line is negative. The $1K that was not allowed - gets carried forward to the next year using the Capital Loss Carryover Worksheet in the instructions to Schedule D. You calculate your NOL using form 1045 schedule A. You can use the form 1045 to apply the NOL to prior 2 years, or you can elect to apply it only to future years (up to 20 years). In what cases, capital loss can be NOL? Never.\"", "title": "" }, { "docid": "266900", "text": "\"The margin money you put up to fund a short position ($6000 in the example given) is simply a \"\"good faith\"\" deposit that is required by the broker in order to show that you are acting in good faith and fully intend to meet any potential losses that may occur. This margin is normally called initial margin. It is not an accounting item, meaning it is not debited from you cash account. Rather, the broker simply segregates these funds so that you may not use them to fund other trading. When you settle your position these funds are released from segregation. In addition, there is a second type of margin, called variation margin, which must be maintained while holding a short position. The variation margin is simply the running profit or loss being incurred on the short position. In you example, if you sold 200 shares at $20 and the price went to $21, then your variation margin would be a debit of $200, while if the price went to $19, the variation margin would be a credit of $200. The variation margin will be netted with the initial margin to give the total margin requirement ($6000 in this example). Margin requirements are computed at the close of business on each trading day. If you are showing a loss of $200 on the variation margin, then you will be required to put up an additional $200 of margin money in order to maintain the $6000 margin requirement - ($6000 - $200 = $5800, so you must add $200 to maintain $6000). If you are showing a profit of $200, then $200 will be released from segregation - ($6000 + $200 = $6200, so $200 will be release from segregation leaving $6000 as required). When you settle your short position by buying back the shares, the margin monies will be release from segregation and the ledger postings to you cash account will be made according to whether you have made a profit or a loss. So if you made a loss of $200 on the trade, then your account will be debited for $200 plus any applicable commissions. If you made a profit of $200 on the trade then your account will be credited with $200 and debited with any applicable commissions.\"", "title": "" } ]
607	Increased diastolic blood pressure (DBP) is associated with abdominal aortic aneurysm.	[ { "docid": "4506414", "text": "BACKGROUND The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. METHODS We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. FINDINGS During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. INTERPRETATION The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. FUNDING Medical Research Council, National Institute for Health Research, and Wellcome Trust.", "title": "Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people" } ]	[ { "docid": "30058568", "text": "CONTEXT Managing thoracic aortic aneurysms identified incidentally by increased use of computed tomography, echocardiography, and magnetic resonance imaging is problematic, especially in the elderly. OBJECTIVE To ascertain whether the previously reported poor prognosis for individuals with thoracic aortic aneurysms has changed with better medical therapies and improved surgical techniques that can now be applied to aneurysm management. DESIGN Population-based cohort study. SETTING AND PATIENTS All 133 patients with the diagnosis of degenerative thoracic aortic aneurysms among Olmsted County, Minnesota, residents between 1980 and 1994 compared with a previously reported cohort of similar patients between 1951 and 1980. MAIN OUTCOME MEASURES The primary clinical end points were incidence, cumulative rupture risk, rupture risk as a function of aneurysm size, and survival. RESULTS In contrast to abdominal aortic aneurysms, for which men are affected predominately, 51% of thoracic aortic aneurysms were identified in women who were considerably older at recognition than men (mean age, 75.9 vs 62.8 years, respectively; P= .01). The overall incidence rate of 10.4 per 100000 person-years (95% confidence interval [CI], 8.6-12.2) between 1980 and 1994 was more than 3-fold higher than the rate from 1951 to 1980. The cumulative risk of rupture was 20% after 5 years. Seventy-nine percent of ruptures occurred in women (P= .01). The 5-year risk of rupture as a function of aneurysm size at recognition was 0% for aneurysms less than 4 cm in diameter, 16% (95% CI, 4%-28%) for those 4 to 5.9 cm, and 31% (95% CI, 5%-56%) for aneurysms 6 cm or more. Overall 5-year survival improved to 56% (95% CI, 48%-66%) between 1980 and 1994 compared with only 19% between 1951 and 1980 (P<.01). CONCLUSIONS In this population, elderly women represent an increasing portion of all patients with clinically recognized thoracic aortic aneurysms and constitute the majority of patients whose aneurysm eventually ruptures. Overall survival for thoracic aortic aneurysms has improved significantly in the past 15 years.", "title": "Improved prognosis of thoracic aortic aneurysms: a population-based study." }, { "docid": "12549585", "text": "Pulse wave velocity (PWV) was measured in the aorta, right leg and arm of 90 control subjects (CS) and 92 hemodialysis patients (HD) of the same age and mean arterial pressure (MAP). Blood chemistry, including blood lipids, and echographic dimensions of the aorta, were measured in all subjects. Presence of aortic calcification was evaluated by abdominal X-ray and echography. Whereas femoral and brachial PWV were only slightly increased in HD (P less than 0.05), the aortic PWV was significantly elevated (1113 +/- 319 cm/sec) in comparison with CS (965 +/- 216 cm/sec; P = 0.0016). Aortic diameters were larger in HD, both at the root of aorta (32.7 +/- 4 vs. 28.2 +/- 2.8 mm; P less than 0.0001) and aortic bifurcation (16.9 +/- 3.1 vs. 14.6 +/- 2.2 mm; P less than 0.0001). Although the MAP was similar in HD (109.9 +/- 19.3 mm Hg) and CS (110.2 +/- 17.2 mm Hg), the pulse pressure was significantly increased in HD patients (76.6 +/- 23.7 vs. 63.9 +/- 22 mm Hg; P = 0.007). In the two populations, aortic PWV was found to increase with age (P less than 0.0001) and MAP (P less than 0.0001). The presence of aortic calcification showed only a borderline relationship with the increase in aortic PWV (P = 0.050 in CS and P = 0.069 in HD). As change in PWV is directly related to change in distensibility, and the aortic diameters were increased in HD, these results indicate that aortic wall compliance is decreased in HD, resulting in an increase in the pulsatile component of arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Aortic and large artery compliance in end-stage renal failure." }, { "docid": "30639847", "text": "CONTEXT Vascular stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Vascular stiffness and blood pressure pulsatility are related; however, temporal relationships between vascular stiffening and blood pressure elevation have not been fully delineated. OBJECTIVE To examine temporal relationships among vascular stiffness, central hemodynamics, microvascular function, and blood pressure progression. DESIGN, SETTING, AND PARTICIPANTS Longitudinal community-based cohort study conducted in Framingham, Massachusetts. The present investigation is based on the 2 latest examination cycles (cycle 7: 1998-2001; cycle 8: 2005-2008 [last visit: January 25, 2008]) of the Framingham Offspring study (recruited: 1971-1975). Temporal relationships among blood pressure and 3 measures of vascular stiffness and pressure pulsatility derived from arterial tonometry (carotid-femoral pulse wave velocity [CFPWV], forward wave amplitude [FWA], and augmentation index) were examined over a 7-year period in 1759 participants (mean [SD] age: 60 [9] years; 974 women). MAIN OUTCOME MEASURES The primary outcomes were blood pressure and incident hypertension during examination cycle 8. The secondary outcomes were CFPWV, FWA, and augmentation index during examination cycle 8. RESULTS In a multivariable-adjusted regression model, higher FWA (β, 1.3 [95% CI, 0.5-2.1] mm Hg per 1 SD; P = .002) and higher CFPWV (β, 1.5 [95% CI, 0.5-2.6] mm Hg per 1 SD; P = .006) during examination cycle 7 were jointly associated with systolic blood pressure during examination cycle 8. Similarly, in a model that included systolic and diastolic blood pressure and additional risk factors during examination cycle 7, higher FWA (odds ratio [OR], 1.6 [95% CI, 1.3-2.0] per 1 SD; P < .001), augmentation index (OR, 1.7 [95% CI, 1.4-2.0] per 1 SD; P < .001), and CFPWV (OR, 1.3 [95% CI, 1.0-1.6] per 1 SD; P = .04) were associated with incident hypertension during examination cycle 8 (338 cases [32%] in 1048 participants without hypertension during examination cycle 7). Conversely, blood pressure during examination cycle 7 was not associated with CFPWV during examination cycle 8. Higher resting brachial artery flow (OR, 1.23 [95% CI, 1.04-1.46]) and lower flow-mediated dilation (OR, 0.80 [95% CI, 0.67-0.96]) during examination cycle 7 were associated with incident hypertension (in models that included blood pressure and tonometry measures collected during examination cycle 7). CONCLUSION In this cohort, higher aortic stiffness, FWA, and augmentation index were associated with higher risk of incident hypertension; however, initial blood pressure was not independently associated with risk of progressive aortic stiffening.", "title": "Aortic stiffness, blood pressure progression, and incident hypertension." }, { "docid": "18997216", "text": "Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.", "title": "Sympathetic baroreflex gain in normotensive pregnant women." }, { "docid": "4890578", "text": "Time for primary reveiw 27 days Atherosclerosis continues to be one of the main subjects in pathology research. The intriguing complexity of its pathogenesis as well as the importance of its clinical sequelae provide a rationale for this [1]. A large number of diseases with totally different clinical presentations are basically atherosclerosis related, and among these, myocardial infarction, stroke, abdominal aneurysms and lower limb ischemia determine to a large extent the morbidity and mortality in Western style populations. But, despite this broad spectrum of clinical disease, most of the acute manifestations of atherosclerosis share a common pathogenetic feature: rupture of an atherosclerotic plaque [2–4]. Plaque disruptions may vary greatly in extent from tiny fissures or erosions of the plaque surface to deep intimal tears which extend into the soft lipid core of lesions; in all these instances, at least some degree of thrombus formation occurs [5, 6]. The abdominal aorta is the arterial site most prominently involved in the process of plaque formation, and also of plaque complications. In this large diameter vessel the process of plaque disruption and thrombosis is not ended by luminal occlusion, and may lead to extensive surface ulcerations comprising large areas of the aortic wall, as can be observed in many autopsy cases at older age. Apart from the undisputable role of atherosclerosis in abdominal aneurysm formation [7], mural thrombosis leads to a surprisingly low rate of clinically significant complications in these patients, although cholesterol emboli can be regularly found in their kidneys and skin at autopsy. Still, it is presently unclear what impact the various biologically active mediators released from eroded aortic surfaces may have on the human body. In contrast, in small diameter vessels such as coronary arteries, occlusive thrombosis is a frequent and often fatal complication of plaque … * Corresponding author. Tel.: +31-20-5665-633; fax: +31-20-914-738; e-mail [email protected]", "title": "Atherosclerotic plaque rupture--pathologic basis of plaque stability and instability." }, { "docid": "8596837", "text": "Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response. Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06). Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.", "title": "Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy" }, { "docid": "6525844", "text": "BACKGROUND Damage to large arteries is a major factor in the high cardiovascular morbidity and mortality of patients with end-stage renal disease (ESRD). Increased arterial stiffness and intima-media thickness, together with increased pulse pressure, are the principal arterial alterations. Whether increased aortic pulse-wave velocity (PWV), a classic marker of increased arterial stiffness, may predict all-cause and/or cardiovascular mortality has never been investigated. METHODS AND RESULTS A cohort of 241 patients with ESRD undergoing hemodialysis was studied between April 1987 and April 1998. The mean duration of follow-up was 72+/-41 months (mean+/-SD). Mean age at entry was 51.5+/-16.3 years. Seventy-three deaths occurred, including 48 cardiovascular and 25 noncardiovascular fatal events. At entry, together with standard clinical and biochemical analyses, patients underwent echocardiography and aortic PWV measured by Doppler ultrasonography. On the basis of Cox analyses, 2 factors emerged as predictors of all-cause and cardiovascular mortality: age and aortic PWV. Hemoglobin and low diastolic pressure interfered to a smaller extent. After adjustment for all the confounding factors, an OR for PWV >12. 0 versus <9.4 m/s was 5.4 (95% CI, 2.4 to 11.9) for all-cause mortality and 5.9 (95% CI, 2.3 to 15.5) for cardiovascular mortality. For each PWV increase of 1 m/s in our study population, all-cause mortality-adjusted OR was 1.39 (95% CI, 1.19 to 1.62). CONCLUSIONS These results provide the first direct evidence that in patients with ESRD, increased aortic stiffness determined by measurement of aortic PWV is a strong independent predictor of all-cause and mainly cardiovascular mortality.", "title": "Impact of aortic stiffness on survival in end-stage renal disease." }, { "docid": "202259", "text": "BACKGROUND Patients undergoing dialysis have a substantially increased risk of cardiovascular mortality and morbidity. Although several trials have shown the cardiovascular benefits of lowering blood pressure in the general population, there is uncertainty about the efficacy and tolerability of reducing blood pressure in patients on dialysis. We did a systematic review and meta-analysis to assess the effect of blood pressure lowering in patients on dialysis. METHODS We systematically searched Medline, Embase, and the Cochrane Library database for trials reported between 1950 and November, 2008, without language restriction. We extracted a standardised dataset from randomised controlled trials of blood pressure lowering in patients on dialysis that reported cardiovascular outcomes. Meta-analysis was done with a random effects model. FINDINGS We identified eight relevant trials, which provided data for 1679 patients and 495 cardiovascular events. Weighted mean systolic blood pressure was 4.5 mm Hg lower and diastolic blood pressure 2.3 mm Hg lower in actively treated patients than in controls. Blood pressure lowering treatment was associated with lower risks of cardiovascular events (RR 0.71, 95% CI 0.55-0.92; p=0.009), all-cause mortality (RR 0.80, 0.66-0.96; p=0.014), and cardiovascular mortality (RR 0.71, 0.50-0.99; p=0.044) than control regimens. The effects seem to be consistent across a range of patient groups included in the studies. INTERPRETATION Treatment with agents that lower blood pressure should routinely be considered for individuals undergoing dialysis to reduce the very high cardiovascular morbidity and mortality rate in this population.", "title": "Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials" }, { "docid": "12513972", "text": "BACKGROUND Intracranial aneurysm (IA) is significantly more prevalent in patients with coarctation of the aorta or bicuspid aortic valve than in the general population, suggesting a common pathophysiology connecting IA and aortopathy. Here, we analyzed echocardiographic aortic root dimension (ARD) in patients with IA to confirm this possibility. METHODS From January 2008 to December 2010, 260 consecutive patients with IA who were admitted to our institution for coil embolization or for acute stroke management and who also underwent echocardiography were enrolled. We hypothesized that patients with large, ruptured, or multiple IAs are more likely to harbor co-prevalent aortopathy as measured by ARD compared to patients with small, isolated, unruptured IAs. Eccentric group was defined as patients aged <55 years with at least one ruptured aneurysm, an aneurysm ≥7 mm in size, or multiple aneurysms; the remainder was classified into a non-eccentric group. Clinical, angiographic, and echocardiographic findings of the two groups were compared. RESULTS ARD was significantly larger in the eccentric group than in the non-eccentric group (P = 0.049), and the difference was confirmed by multivariable analysis (P = 0.02). Subgroup analysis of patients aged <55 years showed similar result for ARD (P = 0.03), whereas hypertension was more associated with the non-eccentric group (P = 0.01). In addition, height was inversely related to aneurysm size after adjustment for age, sex, weight, ARD, smoking status, and number of aneurysms (P = 0.004). CONCLUSIONS A certain group of IA patients share a common intrinsic wall defect with aortopathy. Shared neural crest cell origin may give rise to this phenomenon.", "title": "Echocardiographic Evidence of Innate Aortopathy in the Human Intracranial Aneurysm" }, { "docid": "22730024", "text": "OBJECTIVE To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). METHODS After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. RESULTS In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. CONCLUSIONS Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake.", "title": "Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies." }, { "docid": "24998764", "text": "Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.", "title": "Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension." }, { "docid": "13108582", "text": "Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction. We demonstrated parallel increases in IL-18, OPN expression, and interstitial fibrosis in murine models of left ventricular pressure and volume overload. Exogenous recombinant (r)IL-18 administered for 2 wk increased cardiac OPN expression, interstitial fibrosis, and diastolic dysfunction. Stimulation of the T helper (Th)1 lymphocyte phenotype with a selective toll-like receptor (TLR)9 agonist induced cardiac IL-18 and OPN expression, which was associated with increased cardiac fibrillar collagen concentrations and interstitial fibrosis resulting in diastolic dysfunction. rIL-18 induced OPN expression and protein levels in primary of cardiac fibroblast cultures. Conditioned media from TLR9-stimulated T lymphocyte cultures induced IL-18 and OPN expression in cardiac fibroblasts, while blockade of the IL-18 receptor with a neutralizing antibody abolished the increase in OPN expression. Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts. With pressure overload, IRF1-mutant mice showed downregulation of IL-18 and OPN expression in cardiac tissue, reduced cardiac fibrotic development, and increased left ventricular function compared with wild type. These results provide direct evidence that the induction of IL-18 regulates OPN-mediated cardiac fibrosis and diastolic dysfunction.", "title": "IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice." }, { "docid": "8509018", "text": "BACKGROUND Patients with signs and symptoms of heart failure and a normal left ventricular ejection fraction are said to have diastolic heart failure. It has traditionally been thought that the pathophysiological cause of heart failure in these patients is an abnormality in the diastolic properties of the left ventricle; however, this hypothesis remains largely unproven. METHODS We prospectively identified 47 patients who met the diagnostic criteria for definite diastolic heart failure; all the patients had signs and symptoms of heart failure, a normal ejection fraction, and an increased left ventricular end-diastolic pressure. Ten patients who had no evidence of cardiovascular disease served as controls. Left ventricular diastolic function was assessed by means of cardiac catheterization and echocardiography. RESULTS The patients with diastolic heart failure had abnormal left ventricular relaxation and increased left ventricular chamber stiffness. The mean (+/-SD) time constant for the isovolumic-pressure decline (tau) was longer in the group with diastolic heart failure than in the control group (59+/-14 msec vs. 35+/-10 msec, P=0.01). The diastolic pressure-volume relation was shifted up and to the left in the patients with diastolic heart failure as compared with the controls. The corrected left ventricular passive-stiffness constant was significantly higher in the group with diastolic heart failure than in the control group (0.03+/-0.01 vs. 0.01+/-0.01, P<0.001). CONCLUSIONS Patients with heart failure and a normal ejection fraction have significant abnormalities in active relaxation and passive stiffness. In these patients, the pathophysiological cause of elevated diastolic pressures and heart failure is abnormal diastolic function.", "title": "Diastolic heart failure--abnormalities in active relaxation and passive stiffness of the left ventricle." }, { "docid": "27158570", "text": "We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10(-4)) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13×10(-9)). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10(-12)) and LOC105369882 rs11104632 (P=4.51×10(-8)) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10(-22)) and mean arterial pressure (P=2.86×10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10(-7)), C2orf80 (P<1.00×10(-12)), EPHA6 (P=2.88×10(-7)), SCOC-AS1 (P=4.35×10(-14)), SCOC (P=6.46×10(-11)), CLGN (P=3.68×10(-13)), MGAT4D (P=4.73×10(-11)), ARHGAP42 (P≤1.00×10(-12)), CASP4 (P=1.31×10(-8)), and LINC01478 (P=6.75×10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium.", "title": "Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study." }, { "docid": "19804204", "text": "BACKGROUND AND OBJECTIVES Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. RESULTS Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55). CONCLUSIONS Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.", "title": "Casual blood pressure and neurocognitive function in children with chronic kidney disease: a report of the children with chronic kidney disease cohort study." }, { "docid": "31889025", "text": "OBJECTIVES - To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. DESIGN - Inception cohort study. SETTING - General community. PARTICIPANTS - Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. EXPOSURE MEASURES - Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations. OUTCOME MEASURE - The development of CHF. RESULTS - A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years. CONCLUSIONS - Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.", "title": "The progression from hypertension to congestive heart failure." }, { "docid": "26710772", "text": "Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.", "title": "Sympathetic activation during early pregnancy in humans." }, { "docid": "4647303", "text": "CONTEXT Exposure to cardiovascular risk factors during childhood and adolescence may be associated with the development of atherosclerosis later in life. OBJECTIVE To study the relationship between cardiovascular risk factors measured in childhood and adolescence and common carotid artery intima-media thickness (IMT), a marker of preclinical atherosclerosis, measured in adulthood. DESIGN, SETTING, AND PARTICIPANTS Population-based, prospective cohort study conducted at 5 centers in Finland among 2229 white adults aged 24 to 39 years who were examined in childhood and adolescence at ages 3 to 18 years in 1980 and reexamined 21 years later, between September 2001 and January 2002. MAIN OUTCOME MEASURES Association between cardiovascular risk variables (levels of low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides; LDL-C/HDL-C ratio; systolic and diastolic blood pressure; body mass index; smoking) measured in childhood and adulthood and common carotid artery IMT measured in adulthood. RESULTS In multivariable models adjusted for age and sex, IMT in adulthood was significantly associated with childhood LDL-C levels (P =.001), systolic blood pressure (P<.001), body mass index (P =.007), and smoking (P =.02), and with adult systolic blood pressure (P<.001), body mass index (P<.001), and smoking (P =.004). The number of risk factors measured in 12- to 18-year-old adolescents, including high levels (ie, extreme age- and sex-specific 80th percentile) of LDL-C, systolic blood pressure, body mass index, and cigarette smoking, were directly related to carotid IMT measured in young adults at ages 33 through 39 years (P<.001 for both men and women), and remained significant after adjustment for contemporaneous risk variables. The number of risk factors measured at ages 3 to 9 years demonstrated a weak direct relationship with carotid IMT at ages 24 to 30 years in men (P =.02) but not in women (P =.63). CONCLUSIONS Risk factor profile assessed in 12- to 18-year-old adolescents predicts adult common carotid artery IMT independently of contemporaneous risk factors. These findings suggest that exposure to cardiovascular risk factors early in life may induce changes in arteries that contribute to the development of atherosclerosis.", "title": "Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study." }, { "docid": "13445579", "text": "BACKGROUND AND PURPOSE IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.", "title": "Results of screening for intracranial aneurysms in patients with coarctation of the aorta." }, { "docid": "3552753", "text": "BACKGROUND In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. METHODS Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. RESULTS 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age >/=65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate >/=30/min, low systolic(<90 mm Hg) or diastolic (</=60 mm Hg) Blood pressure), age >/=65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. CONCLUSIONS A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.", "title": "Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study." }, { "docid": "21616324", "text": "BACKGROUND Control of blood pressure (BP) following renal transplantation may improve allograft and patient survival. Our aims were (i) to describe the distribution of BP and the prevalence of systolic and/or diastolic hypertension in children over the first 5 years following renal transplantation and (ii) to evaluate clinical risk factors and centre-specific factors associated with hypertension in this population. METHODS We conducted a retrospective case note review of all current paediatric kidney transplant patients in the UK, with data collected at 6 months, 1, 2 and 5 years following transplantation in subjects with hypertension (systolic and/or diastolic BP > 95th > ) and non-hypertensive subjects BP ≤ 95th > . RESULTS In total, 27.3% (117/428), 27.6% (118/428), 26.0% (95/365) and 25.6% (50/195) of the patients were hypertensive (systolic and/or diastolic BP > 95th > ) at 6 months, 1, 2 and 5 years following transplantation, respectively. A total of 58.4% of the patients at 6 months, 52.8% at 1 year, 48.2% at 2 years and 48.2% at 5 years were receiving anti-hypertensive therapy, of whom 31.6-36.6% remained hypertensive. When subjects were identified as being hypertensive, on anti-hypertensive medication or had untreated hypertension (systolic and/or diastolic BP > 95th > ), 66.4, 61.0, 56.4 and 55.9% of patients were hypertensive at 6 months, 1, 2 and 5 years, respectively. In a multivariate model, odds ratios for systolic hypertension were 4.16 (deceased versus living donor), 2.65 (lowest versus highest quartile of height z-score) and 2.07 (if on anti-hypertensive; yes versus no). There was significant variation in prevalent rates of hypertension between centres (P < 0.0001) that remained significant (P = 0.003) after adjustment for all the factors in the multivariate model. CONCLUSIONS Control of BP after kidney transplantation remains sub-optimal in paediatric centres in the UK. Just over 25% of patients remain hypertensive 5 years following transplantation. Significant differences between centres remain unexplained and may reflect differences in assessment and management of hypertension.", "title": "Systemic arterial hypertension in children following renal transplantation: prevalence and risk factors." }, { "docid": "14121786", "text": "BACKGROUND Epidemiologic analysis of family data on blood pressure (BP) is often compromised by the effects of antihypertensive medications. A review of numerous clinical trials that investigated the effects of BP-lowering medications is summarized here. METHODS Published clinical trials, including 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies with a total of 11,739 participants, were reviewed from PubMed. Six major classes/groups of antihypertensive medications were categorized by ethnicity, including angiotensin-converting enzyme (ACE) inhibitors, alpha1-blockers, cardioselective beta-blockers (beta1-blockers), calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics. RESULTS Using sitting or supine BP, for ethnic groups combined, monodrug therapy with ACE inhibitors showed a weighted average effect of lowering the systolic and diastolic BP by 12.5/9.5 mm Hg; alpha1-blockers by 15.5/11.7 mm Hg; beta1-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. However, ACE inhibitors, alpha1-blockers, and beta1-blockers were less effective in African Americans than in non-African Americans, whereas calcium channel blockers, thiazide diuretics, and loop diuretics were more effective in African Americans than in non-African Americans. For two-drug combination therapy with ethnic groups combined, the BP-lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic BP, respectively. CONCLUSIONS The BP-lowering effects reported here may be used to impute the pretreatment BP levels, which can improve the information content and hence the power of epidemiologic analysis in studies where use of antihypertensive medications is a confounding factor in the BP measurements.", "title": "A summary of the effects of antihypertensive medications on measured blood pressure." }, { "docid": "27449472", "text": "The metabolic syndrome was initially described as an insulin-resistance syndrome characterized by the clustering of metabolic traits such as high triglycerides, low high-density lipoprotein cholesterol, high blood pressure, abdominal obesity and different degrees of impaired glucose regulation. Although different definitions have been developed by various consensus groups, epidemiological studies demonstrate that they all associate the metabolic syndrome with a similar cardiometabolic risk, which is high for diabetes (ranging between three- and 20-fold), depending on the number of components and the inclusion of impaired fasting glucose, impaired glucose tolerance or both. The latter appear to indicate the failure of the beta cell to produce enough insulin to compensate for the increased demand due to insulin resistance. There is a hyperbolic relationship between insulin production and insulin sensitivity, which can be calculated by the disposition index. When this is altered there is a higher risk of developing Type 2 diabetes. There have been no clinical trials in subjects selected by the diagnosis of metabolic syndrome, but structured lifestyle changes have been tested in people with impaired fasting glucose/impaired glucose tolerance and have been able to reduce incident Type 2 diabetes by almost 50%, as long as a weight loss of at least 5% is achieved. Oral antidiabetic and anti-obesity drugs have also been successful to a lesser degree. Some fibrates have reduced or delayed incident diabetes. Extended-release niacin has a neutral effect and statins are controversial. ACE inhibitors and ARBs are the antihypertensive agents least associated with incident diabetes.", "title": "Metabolic syndrome as a risk factor for diabetes." }, { "docid": "25301182", "text": "CONTEXT Limited information exists regarding the role of left ventricular function in predicting exercise capacity and impact on age- and sex-related differences. OBJECTIVES To determine the impact of measures of cardiac function assessed by echocardiography on exercise capacity and to determine if these associations are modified by sex or advancing age. DESIGN Cross-sectional study of patients undergoing exercise echocardiography with routine measurements of left ventricular systolic and diastolic function by 2-dimensional and Doppler techniques. Analyses were conducted to determine the strongest correlates of exercise capacity and the age and sex interactions of these variables with exercise capacity. SETTING Large tertiary referral center in Rochester, Minnesota, in 2006. PARTICIPANTS Patients undergoing exercise echocardiography using the Bruce protocol (N = 2867). Patients with echocardiographic evidence of exercise-induced ischemia, ejection fractions lower than 50%, or significant valvular heart disease were excluded. MAIN OUTCOME MEASURE Exercise capacity in metabolic equivalents (METs). RESULTS Diastolic dysfunction was strongly and inversely associated with exercise capacity. Compared with normal function, after multivariate adjustment, those with moderate/severe resting diastolic dysfunction (-1.30 METs; 95% confidence interval [CI], -1.52 to -0.99; P < .001) and mild resting diastolic dysfunction (-0.70 METs; 95% CI, -0.88 to -0.46; P < .001) had substantially lower exercise capacity. Variation of left ventricular systolic function within the normal range was not associated with exercise capacity. Left ventricular filling pressures measured by resting E/e' of 15 or greater (-0.41 METs; 95% CI, -0.70 to -0.11; P = .007) or postexercise E/e' of 15 or greater (-0.41 METs; 95% CI, -0.71 to -0.11; P = .007) were similarly associated with a reduction in exercise capacity, each in separate multivariate analyses. Individuals with impaired relaxation (mild dysfunction) or resting E/e' of 15 or greater had a progressive increase in the magnitude of reduction in exercise capacity with advancing age (P < .001 and P = .02, respectively). Other independent correlates of exercise capacity were age (unstandardized beta coefficient, -0.85 METs; 95% CI, -0.92 to -0.77, per 10-year increment; P < .001), female sex (-1.98 METs; 95% CI, -2.15 to -1.84; P < .001), and body mass index greater than 30 (-1.24 METs; 95% CI, -1.41 to -1.10; P < .001). CONCLUSION In this large cross-sectional study of those referred for exercise echocardiography and not limited by ischemia, abnormalities of left ventricular diastolic function were independently associated with exercise capacity.", "title": "Left ventricular function and exercise capacity." }, { "docid": "3825750", "text": "BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. We evaluated the renoprotective effects of dual blockade of the renin-angiotensin-aldosterone system by adding treatment with aliskiren, an oral direct renin inhibitor, to treatment with the maximal recommended dose of losartan (100 mg daily) and optimal antihypertensive therapy in patients who had hypertension and type 2 diabetes with nephropathy. METHODS We enrolled 599 patients in this multinational, randomized, double-blind study. After a 3-month, open-label, run-in period during which patients received 100 mg of losartan daily, patients were randomly assigned to receive 6 months of treatment with aliskiren (150 mg daily for 3 months, followed by an increase in dosage to 300 mg daily for another 3 months) or placebo, in addition to losartan. The primary outcome was a reduction in the ratio of albumin to creatinine, as measured in an early-morning urine sample, at 6 months. RESULTS The baseline characteristics of the two groups were similar. Treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-to-creatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). A small difference in blood pressure was seen between the treatment groups by the end of the study period (systolic, 2 mm Hg lower [P=0.07] and diastolic, 1 mm Hg lower [P=0.08] in the aliskiren group). The total numbers of adverse and serious adverse events were similar in the groups. CONCLUSIONS Aliskiren may have renoprotective effects that are independent of its blood-pressure-lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. (ClinicalTrials.gov number, NCT00097955 [ClinicalTrials.gov].).", "title": "Aliskiren combined with losartan in type 2 diabetes and nephropathy." }, { "docid": "19854543", "text": "PURPOSE To characterize the relationship between aneurysm size and epidemiologic risk factors with growth and rupture by using computed tomographic (CT) angiography. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board approved study, patients with known asymptomatic unruptured intracerebral aneurysms were followed up longitudinally with CT angiographic examinations. Growth was defined as an increase in one or more dimensions above the measurement error, and at least 5% volume by using the ABC/2 method. Associations of epidemiologic factors with aneurysm growth and rupture were analyzed by using logistic regression analysis. Intra- and interobserver agreement coefficients for dimension, volume, and growth were evaluated by using the Pearson correlation coefficient and difference of means with 95% confidence intervals, the agreement statistic, and the McNemar χ(2). RESULTS Patients (n = 165) with aneurysms (n = 258) had a mean follow-up time of 2.24 years from time of diagnosis. Forty-six of 258 (18%) aneurysms in 38 patients grew larger. Spontaneous rupture occurred in four of 228 (1.8%) intradural aneurysms of average size (6.2 mm). Risk of aneurysm rupture per patient-year was 2.4% (95% CI: 0.5%, 7.12%) with growth and 0.2% (95% CI: 0.006%, 1.22%) without growth (P = .034). There was a 12-fold higher risk of rupture for growing aneurysms (P < .002), with high intra- and interobserver correlation coefficients for size, volume, and growth. Tobacco smoking (3.806, one degree of freedom; P < .015,) and initial size (5.895, two degrees of freedom; P < .051) were independent covariates, predicting 78.4% of growing aneurysms. CONCLUSION These results support imaging follow-up of all patients with aneurysms, including those whose aneurysms are smaller than the current 7-mm treatment threshold. Aneurysm growth, size, and smoking were associated with increased rupture risk.", "title": "Natural history of asymptomatic unruptured cerebral aneurysms evaluated at CT angiography: growth and rupture incidence and correlation with epidemiologic risk factors." }, { "docid": "24396137", "text": "Older cancer survivors are a vulnerable population due to an increased risk for chronic diseases (e.g., cardiovascular disease) compounded with treatment late-effects and declines in physical functioning. Therefore, interventions that reduce chronic disease risk factors (i.e., blood pressure, chronic inflammation, and cortisol) are important in this population. Tai chi chih (TCC) is a mind-body exercise associated with reductions in chronic disease risk factors, but has not been examined with older cancer survivors. In a feasibility randomized controlled trial of TCC, we examined secondary outcomes of blood pressure, salivary cortisol, and inflammatory cytokines (interleukin (IL)-6, IL-12, tumor necrosis factor-α, IL-10, IL-4) due to their implications in chronic diseases. Sixty-three senior female cancer survivors (M age = 67 years, SD = 7.15) with physical functioning limitations (SF-12 physical functioning ≤80 or role-physical ≤72) were randomized to 12-weeks (60-min, three times a week) of TCC or Health Education control (HEC) classes. Resting blood pressure, 1-day salivary cortisol samples, and fasting plasma samples for cytokine multiplex assays were collected at baseline and 1-week post-intervention. Controlling for baseline values, the TCC group had significantly lower systolic blood pressure (SBP, p = 0.002) and cortisol area-under-curve (AUC, p = 0.02) at post-intervention than the HEC group. There was no intervention effect on inflammatory cytokines (p’s > 0.05). This TCC feasibility trial was associated with significant reductions in SBP and cortisol AUC in senior female cancer survivors. Larger, definitive trials are needed to confirm these findings. Senior survivors’ have an increased risk for chronic diseases; however, TCC interventions may help reduce associated risk factors.", "title": "Blood pressure, salivary cortisol, and inflammatory cytokine outcomes in senior female cancer survivors enrolled in a tai chi chih randomized controlled trial" }, { "docid": "2774906", "text": "Physical activity protects against cardiovascular disease, and physiological cardiac hypertrophy associated with regular exercise is usually beneficial, in marked contrast to pathological hypertrophy associated with disease. The p110alpha isoform of phosphoinositide 3-kinase (PI3K) plays a critical role in the induction of exercise-induced hypertrophy. Whether it or other genes activated in the athlete's heart might have an impact on cardiac function and survival in a setting of heart failure is unknown. To examine whether progressive exercise training and PI3K(p110alpha) activity affect survival and/or cardiac function in two models of heart disease, we subjected a transgenic mouse model of dilated cardiomyopathy (DCM) to swim training, genetically crossed cardiac-specific transgenic mice with increased or decreased PI3K(p110alpha) activity to the DCM model, and subjected PI3K(p110alpha) transgenics to acute pressure overload (ascending aortic constriction). Life-span, cardiac function, and molecular markers of pathological hypertrophy were examined. Exercise training and increased cardiac PI3K(p110alpha) activity prolonged survival in the DCM model by 15-20%. In contrast, reduced PI3K(p110alpha) activity drastically shortened lifespan by approximately 50%. Increased PI3K(p110alpha) activity had a favorable effect on cardiac function and fibrosis in the pressure-overload model and attenuated pathological growth. PI3K(p110alpha) signaling negatively regulated G protein-coupled receptor stimulated extracellular responsive kinase and Akt (via PI3K, p110gamma) activation in isolated cardiomyocytes. These findings suggest that exercise and enhanced PI3K(p110alpha) activity delay or prevent progression of heart disease, and that supraphysiologic activity can be beneficial. Identification of genes important for hypertrophy in the athlete's heart could offer new strategies for treating heart failure.", "title": "Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy." }, { "docid": "597790", "text": "Although mast cell functions have classically been related to allergic responses, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm and cancer. This study presents evidence that mast cells also contribute to diet-induced obesity and diabetes. For example, white adipose tissue (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Furthermore, in the context of mice on a Western diet, genetically induced deficiency of mast cells, or their pharmacological stabilization, reduces body weight gain and levels of inflammatory cytokines, chemokines and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer experiments of cytokine-deficient mast cells show that these cells, by producing interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), contribute to mouse adipose tissue cysteine protease cathepsin expression, apoptosis and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance. Our results showing reduced obesity and diabetes in mice treated with clinically available mast cell-stabilizing agents suggest the potential of developing new therapies for these common human metabolic disorders.", "title": "Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice" }, { "docid": "8529693", "text": "In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.", "title": "Maternal and child undernutrition: consequences for adult health and human capital" } ]
4503	Events that cause major movement in forex?	[ { "docid": "379547", "text": "Trading Speeches can be difficult, 1 comment can be bullish then next phrase bearish. However language algorithms can process the tone of the entire message before you can read the first word or have even finished downloading the text of the statement. The biggest news is the 1st Friday of the month, the non-farm payrolls out of the USA. You used to be able to get the news before the price moved, but high-frequency algos changed all that, essentially the exchanges get quote stuffed, so good luck unless you are using a bucketshop. Better to wait for a pull back from the initial reaction if the numbers are good, otherwise you will get a fill at the peak. If the numbers are a big deviation from expectations then you can just jump in. Back in 2006 the Bank of England raised interest rates when it wasn't expected and the GBPUSD flew 500 pips. This Forex calendar has charts of every news release, so you can see what to expected based on what has happened in the past with a certain bit of economic news. http://www.fasteconomicnews.com/fx_calendar.aspx", "title": "" }, { "docid": "582063", "text": "Look for unsustainable policies and actions by policy makers, both before and possibly during, when looking at the ForEx markets. Consider some examples: Each of those events could be seen in the growing unsustainability of local policies. ForEx markets and local policies can appear to stay on an unsustainable path for a long time, but equilibrium will force itself on everything in the long run. In two of the above cases, the initial response wasn't enough to offset the mess, and more and more intervention had to be done, only making matters worse. When you know how unsustainable policies are and how big the corrections need to be, you can quickly ascertain whether an action by policy makers will be enough.", "title": "" }, { "docid": "452434", "text": "Sometimes the market has to be left alone. Too much interference of the policy makers to stabilize the falling market can actually result in a major crisis. Every change stabilises after sometime and it is also applicable in the Forex trading market. So, the eager investors should learn to have some patience and wait for the market to stabilise itself rather than make random predictions on the policies released by policy makers", "title": "" }, { "docid": "319996", "text": "Anything related to the central bank will have a large impact, as they are the ones who determine interest rates, and interest rates have a big effect on currency flows. GDP is also important, as when there is an economic slowdown it may result in the central bank reducing rates to boost economic activity. The opposite is also true, large increases in GDP may mean that an interest rate hike might be needed. Inflation data is also very important. Again, large changes in inflation either way may push the central bank towards changing rates. This data typically is in the form of CPI Note that each central bank is different. They all have specific mandates and specific pieces of economic data that they place emphasis on. The Federal Reserve as of late has closely been watching inflation data, especially wage inflation data, and employment. Significant deviations in these data points from whats expected by investors can greatly move the market. However, these specific factors are a little less important for, say, Mexico, which is mostly concerned with headline inflation. Read the statements issued by the central banks to find out whats important to them. Central banks also issue expectations for things like growth, CPI, etc. If these expectations are not met, it may result in a policy change, or at least talk of a policy change, at the next meeting of the central bank. Anticipating these policy changes and trading accordingly is one strategy to be a profitable forex trader Also, there are several forex news calendars online that indicate what is likely to be high impact news. These can be helpful starting out.", "title": "" }, { "docid": "124254", "text": "It's impossible to determine which event will cause a major shift for a certain currency pair. However, this does not mean that it's not possible to identify events that are important to the overall market sentiment and direction. There are numerous sites that provide a calendar for upcoming and past events and their impact which is most of the time indicated as low, medium and high. Such sites are: Edit: I would like to add to that, that while these are major market movers, you cannot forget that they mainly provide a certain direction for the market but that it's not always clear in which direction the market will go. A recent and prime example of a major event that triggered opposite effects of what you would expect, is the ECB meeting that took place the 3rd of December. Due to the fact that the market already priced in further easing by the ECB the euro strengthened instead of weakening compared to the dollar. This strengthening happened even though the ECB did in fact adjust the deposit by 10 base points to -0.30 % and increased the duration of the QE. Taking above example into consideration it's important to always remember that fundamentals are hard to grasp and that it will take a while to make it a second nature and become truly successful in this line of trading. Lastly, fundamentals are only a part of the complete picture. Don't lose sight of support and resistance levels as well as price action to determine when and how to enter a trade.", "title": "" }, { "docid": "489509", "text": "currency's central bank or treasury/finance department speeches that can announce a significant change in policy. That includes: Particularly when it is a high level figure within the department such as the President or Prime Minister making the announcement. Macroeconomic stats: GeoPolitical considerations, such as: Economic calendars, such as ForexFactory and MyFxBook track planned economic news releases. Obviously, a coup d'etat or war declaration may not be well known in advance.", "title": "" } ]	[ { "docid": "248794", "text": "Forex is really not that volatile compared to other major asset classes like stocks and commodities. But still markets are generally unencumbered in the major pairs and therefore spikes in volatility can happen. Take what happened with the Swiss Franc a few years ago for example, or GBPUSD recently with news of Brexit. This is less the case with highly regulated currencies like the Chinese Yuan (CNY) Volatility is caused by excessive buy or sell pressure in relation to the available liquidity at the current price. This is usually caused by large buy or sell orders placed with interbank desks by institutions (often including other banks) and central banks. News can also sometimes have a dramatic impact and cause traders to adjust their prices significantly and very quickly.", "title": "" }, { "docid": "389562", "text": "If the period is consistent for company X, but occurs in a different month as Company Y, it might be linked to the release of their annual report, or the payment of their annual dividend. Companies don't have to end their fiscal year near the end of the Calendar year, therefore these end of year events could occur in any month. The annual report could cause investors to react to the hard numbers of the report compared to what wall street experts have been predicting. The payment of an annual dividend will also cause a direct drop in the price of the stock when the payment is made. There will also be some movement in prices as the payment date approaches.", "title": "" }, { "docid": "241059", "text": "\"NASDAQ has Pre and After market : NASDAQ Trading Schedule Regular Trading Session Schedule The NASDAQ Stock Market Trading Sessions (Eastern Time) Pre-Market Trading Hours from 4:00 a.m. to 9:30 a.m. Market Hours from 9:30 a.m. to 4:00 p.m. After-Market Hours from 4:00 p.m. to 8:00 p.m. Quote and order-entry from 4:00 a.m. to 8:00 p.m. Quotes are open and firm from 4:00 a.m. to 8:00 p.m. You can trade in Pre/After Market but liquidity is very low. If an \"\"unexpected world events\"\" occurs, the volume/liquidity will most certainly increase. Another example is the Forex Market that's open 24/7 around the world. As one major forex market closes, another one opens. According to GMT, for instance, forex trading hours move around the world like this: available in New York between 01:00 pm – 10:00 pm GMT; at 10:00 pm GMT Sydney comes online; Tokyo opens at 00:00 am and closes at 9:00 am GMT; and to complete the loop, London opens at 8:00 am and closes at 05:00 pm GMT. This enables traders and brokers worldwide, together with the participation of the central banks from all continents, to trade online 24 hours a day. src\"", "title": "" }, { "docid": "594655", "text": "\"Forex. I will employ my skill for \"\"suspension of disbelief\"\" and answer with no visceral reaction to Bitcoin itself. The Euro is not an 'investment.' It's a currency. People trade currencies in order to capture relative movements between pairs of currencies. Unlike stocks, that have an underlying business and potential for growth (or failure, of course) a currency trade is a zero sum game, two people on opposite sides of a bet. Bitcoin has no underlying asset either, no stock, no commodity. It trades, de facto, like a currency, and for purposes of objective classification, it would be considered a currency, and held similar to any Forex position.\"", "title": "" }, { "docid": "277074", "text": "It isn't that the companies force traders, it is more the other way around. Traders wouldn't trade without margin. The main reason is liquidity and taking advantage of minor changes in the forex quotes. It goes down to pips and traders make profit(loss) on movement of pips maybe by 1 or 2 and in some cases in 1/1000 or less of a pip. So you need to put in a large amount to make a profit when the quotes move up or down. Supposedly if they have put in all the amount upfront, their trading options are limited. And the liquidity in the market goes out of the window. The banks and traders cannot make a profit with the limited amount of money available at their disposal. So what they would do is borrow from somebody else, so why not the broker itself in this case maybe the forex company, and execute the trades. So it helps everybody. Forex companies make their profit from the fees, more the trades done, more the fees and hence more profit. Traders get to put their fingers in many pies and so their chances of making profits increases. So everybody is happy.", "title": "" }, { "docid": "195206", "text": "If you are in a position to have information that will impact the shares of a stock or index fund and you use that information for either personal gain or to mitigate the losses that you would have felt then it is insider trading. Even if in the end your quiet period passes with little or no movement of the stocks in question. It is the attempt to benefit from or the appearance of the attempt to benefit from inside information that creates the crime. This is the reason for the quiet periods to attempt to shield the majority of the companies employees from the appearance of impropriety, as well as any actual improprieties. With an index you are running a double edged sword because anything that is likely to cause APPLE to drop 10% is likely to give a bump to Motorola, Google, and its competitors. So you could end up in jail for Insider trading and lose your shirt on a poor decision to short a Tech ETF on knowledge that will cause Apple to take a hit. It is certainly going to be harder to find the trade but the SEC is good at looking around for activity that is inconsistent with normal trading patterns of individuals in a position to have knowledge with the type of market impact you are talking about.", "title": "" }, { "docid": "558670", "text": "The idea behind this move is to avoid or mitigate long-term deflationary pressure and to boost the competitiveness of Swiss exporters. This is primarily a Swiss-based initiative that does not appear likely to have a major impact on the broader Eurozone. However, some pressure will be felt by other currencies as investors look to purchase - ie. this is not a great scenario for other countries wanting to keep their currencies weak. In terms of personal wealth - if you hold Swiss f then you are impacted. However, 1.2 is still very strong (most analysts cite 1.3 as more realistic) so there seems little need for a reaction of any kind at the personal level at this time, although diversity - as ever - is good. It should also be noted that changing the peg is a possibility, and that the 1.3 does seem to be the more realistic level. If you hold large amounts of Swiss f then this might cause you to look at your forex holdings. For the man in the street, probably not an issue.", "title": "" }, { "docid": "405276", "text": "One interpretation of the above is that Pound (alongside US Dollar, Euro and other major curriencies), which forms the Forex basket of countries has dropped to less than 10% weightage in case of China's Forex holding. Now the question is where did this money go, this money probably have gone into Forex market to buy Yuan against Pound/Dollar etc. to bolster or strengthen Yuan. The currency reserve management is the 'wealth' management part and the 'currency' management part is what is known as 'central bank intervention' to stabilize the currency.", "title": "" }, { "docid": "222135", "text": "You cannot lose more than what you have in your account (equity). You'll get margin called. No broker will allow you to go negative, at least if they aren't caught off guard like when the Swiss decided to decouple their currency. If you want to understand the basics of forex I suggest you read the following: http://www.babypips.com/school This part explains the basics about leverage and margin. They do a good job so no need in repeating it here: http://www.babypips.com/school/undergraduate/senior-year/the-number-1-cause-of-death-of-forex-traders/leverage-defined.html You you need to keep the following in mind when trading forex:", "title": "" }, { "docid": "283774", "text": "There aren't and for a good reason. The long term trend of INR against USD, GBP, EUR and other harder currencies is down. Given the inflation differential between these economies and India's, fund managers and investors should expect this to continue. Therefore, if you are invested for any reasonable length of time, you would expect the forex movements to add to your returns. Historically, this has been true of international funds run in India.", "title": "" }, { "docid": "121886", "text": "\"The price of a company's stock at any given moment is established by a ratio of buyers to sellers. When the sellers outnumber the buyers at a given price, the stock price drops until there are enough people willing to buy the stock to balance the equation again. When there are more people wanting to purchase a stock at a given price than people willing to sell it, the stock price rises until there are enough sellers to balance things again. So given this, it's easy to see that a very large fund (or collection of very large funds) buying or selling could drive the price of a stock in one direction or another (because the sheer number of shares they trade can tip the balance one way or another). What's important to keep in mind though is that the ratio of buyers to sellers at any given moment is determined by \"\"market sentiment\"\" and speculation. People selling a stock think the price is going down, and people buying it think it's going up; and these beliefs are strongly influenced by news coverage and available information relating to the company. So in the case of your company in the example that would be expected to triple in value in the next year; if everyone agreed that this was correct then the stock would triple almost instantly. The only reason the stock doesn't reach this value instantly is that the market is split between people thinking this is going to happen and people who think it won't. Over time, news coverage and new information will cause one side to appear more correct than the other and the balance will shift to drive the price up or down. All this is to say that YES, large funds and their movements CAN influence a stock's trading value; BUT their movements are based upon the same news, information, analysis and sentiment as the rest of the market. Meaning that the price of a stock is much more closely tied to news and available information than day to day trading volumes. In short, buying good companies at good prices is just as \"\"good\"\" as it's ever been. Also keep in mind that the fact that YOU can buy and sell stocks without having a huge impact on price is an ADVANTAGE that you have. By slipping in or out at the right times in major market movements you can do things that a massive investment fund simply cannot.\"", "title": "" }, { "docid": "511647", "text": "\"This page from TripAdvisor may be of interest. Look at what fees are charged on your ATM cards and credit cards, and consider overpaying your credit card so you have a credit balance that you can draw on for cash \"\"advances\"\" from ATMs that will dispense in local currency. Depending on what fees your bank charges, you may get a better rate than the forex cash traders at the airport. Edit: Cards may not always have the best rate. I recently heard from a traveler who was able to use a locally but not globally dominant currency to buy cash of a major currency at a shopping mall (with competitive forex traders) at rates even better than the mid-market rates posted at xe.com and similar places; I don't think you'll have that experience going from Australia to Malaysia (but another traveler reading this might have a different pair). In my experience the card rates are slightly worse than those and the airport forex traders significantly worse.\"", "title": "" }, { "docid": "434925", "text": "\"If markets are efficient they will be unpredictable. If all past information is already priced into a stock then movement will only occur when new information is introduced. Since no one can predict future events stocks will move in an unpredictable way. If markets are inefficient in the short term, people should be able to figure out the long-term price movements. This doesn't seem to be the case. This is why the authoritative book on market efficiency is called \"\"A Random Walk Down Wall Street\"\".\"", "title": "" }, { "docid": "428652", "text": "\"I think the issue here is the rules say that \"\"relevant current events in finance\"\" are acceptable when (I think) that wording is too loose. \"\"Current events in finance\"\" is just very, very general, and anything related to central banking, monetary or fiscal policy, global austerity, analysis of index movements, sovereign defaults (and speculation thereof) qualifies a \"\"current events in finance\"\" - so technically, the rules aren't being broken. I think that having the language tightened a bit would help set the subreddit tone a little more accurately.\"", "title": "" }, { "docid": "76466", "text": "\"It looks like these types of companies have to disclose the health of their accounts to CFTC (Commodity Futures Trading Commission). That is the gist I get at least from this article about the traders that lost money due to the Swiss removing the franc’s cap against the euro. The article says about the U.S. retail FOREX brokerage: Most of FXCM’s retail clients lost money in 2014, according to the company’s disclosures mandated by the CFTC. The percentage of losing accounts climbed from 67 percent in the first and second quarters to 68 percent in the third quarter and 70 percent in the fourth quarter. Side note: The Swiss National Bank abandoned the cap on the currency's value against the euro in mid-January 2015. But above paragraph provides data on FXCM’s retail clients in 2014. It could consequently be concluded that, even without \"\"freak events\"\" (such as Switzerland removing the franc cap), it is more likely for an investor to NOT make a profit on the FOREX market. This is also in line with what \"\"sdfasdf\"\" and \"\"Dario Fumagalli\"\" say in their answers.\"", "title": "" }, { "docid": "259440", "text": "\"Overall, since gold has value in any currency (and is sort of the ultimate reserve currency), why would anyone want to currency hedge it? Because gold is (mostly) priced in USD. You currency hedge it to avoid currency risk and be exposed to only the price risk of Gold in USD. Hedging it doesn't mean \"\"less speculative\"\". It just means you won't take currency risk. EDIT: Responding to OP's questions in comment what happens if the USD drops in value versus other major currencies? Do you think that the gold price in USD would not be affected by this drop in dollar value? Use the ETF $GLD as a proxy of gold price in USD, the correlation between weekly returns of $GLD and US dollar index (measured by major world currencies) since the ETF's inception is around -47%. What this says is that gold may or may not be affected by USD movement. It's certainly not a one-way movement. There are times where both USD and gold rise and fall simultaneously. Isn't a drop in dollar value fundamentally currency risk? Per Investopedia, currency risk arises from the change in price of one currency in relation to another. In this context, it's referring to the EUR/USD movement. The bottom line is that, if gold price in dollar goes up 2%, this ETF gives the European investor a way to bring home that 2% (or as close to that as possible).\"", "title": "" }, { "docid": "36438", "text": "Regarding some major holes in The Atlantic article... One, Longwall mining became the norm underground rather than advance-retreat mining. It massively advanced the productive output of the industry, and required far less workforce. This was THE central cause of the precipitous drop to the coal industry workforce before the 1990s. Thereafter, a confluence of prices, competition, attacks on the working class/unions, of new energy sources, etc and other factors were the mixture which reduced the workforce. Two, strip mining (and lignite-type coal; lower workforce necessary) in the Western coal region also played a role rather than the demands of underground mining (mostly bituminous, but also anthracite-type coal, concentrated in the East; higher workforce necessary). Key to remember that this move from eastern to western coal production, while reducing the workforce, was a major drive by the coal bosses in the 90s through the 2000s. A major aspect was that this was a campaign by the owners/bosses seeking to side-step the UMWA and unions/labor costs/health/dental. The eastern mines were dominantly Union, but out west, the union movement in the coal industry unfortunately never had broad modern success. Moments of greatness occurred in the western UMWA organizing battles (some great Navjao nation unionists, some good locals in Colorado too, a few valiant UT battles – one in particular which was lead by miners who were originally from Mexico), but no where near like east of the Mississippi. Three. Anyone who worked or even lived near the industry (lived in Appalachia or Western Coal), could have told the young Atlantic author, or the Stanford Institute fellow just about all of this. Driving around rural West Virginia, PA, or Kentucky you can occasionally see the old advance-retreat Joy 'miner' machinery littering the countryside. Old-timers often times are glad to share heaps of the proud labor history of the region and this industry. Much easier to make a buck via The Atlantic by reading a couple academic reports, check Department of Energy, MSHA, and BLS statistical websites.", "title": "" }, { "docid": "287563", "text": "Bitcoin prices are likely rising as a result of the simple issue of supply and demand. Supply is constrained as there aren't much in the way of new bitcoins coming into existence, and demand is high right now as a result of various events. For example, this Reuters article goes into some detail as to some current influences. Mostly, crypto-hedge funds are buying a lot of bitcoins as a speculative move (i.e., believing the price will continue to rise). The evidence suggests that few of the users are buying bitcoin to use it as a means of exchange, but are speculating to increase their capital. Many describe the bubble as similar to the Tulip craze in seventeenth century Holland; from the same Reuters article: “It’s got all the shapings of your tulip bubble chart (but) that tells you nothing about where that price line could go depending on the number of people who wish to own it,” Standard Life’s head of investment strategy, Andrew Milligan, said on Wednesday. “Who is to say it doesn’t reach $100,000?” You can see in the volume chart from blockchain.info that the trading volume for bitcoins has really increased - and if you look at the market price, you see a very similar movement. However, if you look at the number of transactions per day, that number is basically constant - meaning the actual uses of bitcoins by people just buying or selling goods or services isn't really changing much, but the dollar amount is. That's indicative of a speculation-caused bubble. Below is a graph I made from the data from blockchain.info above that overlays price with trading volume; you can see clearly the increase in volume and increase in price are nearly simultaneous. Bitcoin itself has some actual utility, mostly for black market sellers and similar people participating in activities that are less than legal (not necesesarily ethically bad, for example people in nations with oppressive regimes that limit contact with the outside world or try to restrict foreign currency purchases). It's unlikely that the degree of adoption so far however has driven it to this level, and the fact that bitcoin can be broken up into very small chunks means that the big boom in price of individual bitcoins causes the demand-side pressure from the actual use of bitcoins to be alleviated (as there is now 1/10th the demand for bitcoins from people who use them for non-speculative reasons).", "title": "" }, { "docid": "19367", "text": "With your experience, I think you'd agree that trading over a standardized, regulated exchange is much more practical with the amount of capital you plan to trade with. That said, I'd highly advise you to consider FX futures at CME, cause spot forex at the bucket shops will give you a ton of avoidable operational risks.", "title": "" }, { "docid": "72372", "text": "Stock values are generally reflective of a company's overall potential; and to some extent investor confidence in the prospect of a continued growth of that potential. Sales over such a short period of time such as a single weekend do not noticeably impact a stock's valuation. A stock's value has more to do with whether or not they meet market expectations for sales over a certain period of time (generally 1 quarter of a year) than it does that they actually had sales (or profits) on any given day. Of course, catastrophic events, major announcements, or new product releases do sometimes cause significant changes in a stock's value. For this reason you will often see stocks have significant volatility in periods around earnings announcements, merger rumors, or when anything unexpected happens in the world that might benefit or hurt their potential sales and growth. But overall a normal, average weekend of sales is already built into the price of a stock during normal trading.", "title": "" }, { "docid": "290441", "text": "\"Thank God you have your child back, it is so awesome that you finally found a medical treatment that worked. It must have been a truly trying time in your lives. That situation is an important template in personal finance. Through no fault of your own, a series of events occurred that caused you to spend far more money then you anticipated. Per your post this was complicated by lost income due to economic situations. What is to say that this does not happen again in the future? While we can all hope that our child does not get sick, there are other events that could also fit into this template. Because of this I hate all options you present. Per your post, you are pretty thin with free cash flow and have high income, and yet you are looking to borrow more. That is a recipe for disaster with it being made worse as you are considering putting your home at risk. The 20K per year per kid sounds like a live at the university state school; or, a close by private school. Your finances do not support either option. There are times when the word \"\"No\"\" is in order when answering questions. Doing a live at home community college to university will cost you a total of about 30K per kid rather than the 80K you are proposing. Doing this alone will greatly reduce the risk you are attempting to assume. Doing that and having your child work some, you could cash flow college. That is what I would recommend. Given that you are so thin, you will also have to put constraints on college attendance. No changing major three times, only majors with an employable skills, and studying before partying. It may be worth it to wait a year of two before attending if a decision cannot be made. I was in a similar situation when my son started college. High income, but broke. He worked and went to a community college and was able to pay for the bulk of it himself. From there he obtained a job with a healthy salary and completed his degree at the University. It took him a little longer, but he is debt free and has a fantastic work ethic.\"", "title": "" }, { "docid": "241860", "text": "One thing I like to do every once in a while is look at the day's market movers. It's a list of symbols that had huge movement. There tend to be a couple of 50+% movers every time I look. In fact today I see ATV moved up 414.48%: So there it is—doubling your investment in one day and then some is technically possible. The problem is that the market movers chart also has an equal number of symbols that had major movements in the other direction. Today's winner is: SPCB lost 40% in one day, and thats the problem. If you invest in anything that can double your investment in one year, it can also halve your investment in one year. Or do better. Or do worse. You really don't know because the volatility is so high.", "title": "" }, { "docid": "69419", "text": "I used Oanda.com for Forex trading a couple years ago. I am in the US but I think it's available in the UK as well. At the time, they had no commissions and their spreads were comparable or better than other brokers. The spreads would just quite considerably when a big event like a Fed meeting or the unemployment figures come out, but I suspect that that is the same everywhere (or they have constant spreads and reject trades). They did not push the high leverages like other brokers were at the time. I considered this to be very reputable, because though the profits to be gotten through 100:1 leverage are great advertising, the reality is that one unexpected spike and a newbie would lose a bunch of money in a margin call.", "title": "" }, { "docid": "497174", "text": "ETFs have caused many if not most stocks on the SP500 to become correlated. I think at some point in the last couple of years, 90% of the SP500 were correlated to the index itself. So you're going to see a lot of movement together of most stocks.", "title": "" }, { "docid": "278616", "text": "\"Funny you mentioned \"\"the protestors are here already,\"\" since they're cause is already a lost one. As you mentioned, everything will be on sale; those that already have excess income will be able to gobble up discounted assets, while those that are already in financial trouble (a la OWS protestors) will be left in the dust asset-wise, and if/when they recover the discount period will long be over. Hence, the wealth gap will continue to widen, despite the OWS movement's passionate--yet uninformed and fruitless cause. Also, I liked your ideas on guns. Arms and ammunition are--and especially will be in case of a tumultuous future period--a precious commodity in themselves and prove to be a wise investment, even if they only end up being used as a hobby only.\"", "title": "" }, { "docid": "445939", "text": "There's two types of categories at play that define currency types - but I think the first is more like what you are after. The first is there are essentially three currency types now recognised - see them described here: http://finance.mapsofworld.com/money/types/ The second is currencies can be categorised by the type of economy from which they are generated (reserve/commodity/etc) - see them described here: http://www.forextraders.com/learn-forex-trading-course/major-currency-pairs.html", "title": "" }, { "docid": "84870", "text": "My interpretation of that sentence is that you can't do the buying/selling of shares outright (sans margin) because of the massive quantity of shares he's talking about. So you have to use margin to buy the stocks. However, because in order to make significant money with this sort of strategy you probably need to be working dozens of stocks at the same time, you need to be familiar with portfolio margin. Since your broker does not calculate margin calls based on individual stocks, but rather on the value of your whole portfolio, you should have experience handling margin not just on individual stock movements but also on overall portfolio movements. For example, if 10% (by value) of the stocks you're targeting tend to have a correlation of -0.8 with the price of oil you should probably target another 10% (by value) in stocks that tend to have a correlation of +0.8 with the price of oil. And so on and so forth. That way your portfolio can weather big (or even small) changes in market conditions that would cause a margin call on a novice investor's portfolio.", "title": "" }, { "docid": "373442", "text": "\"No, you're glossing over some very interesting issues here (as did ZH... very disappointed... shocked, really). Here's the bottom line: due to the USA's particular brand of fucked up foreign policy, foreign relations actions in one part of the world have produced an unexpected outcome due to the USA's neglect to take care of business on the other side of the world. That outcome was one of Russia's largest state oil companies ending up with majority ownership of an American going interest, Citgo. Now it looks pretty fucking odd when Russia, a country currently experiencing USA imposed sanctions, ends up owning American refineries that could be used to basically make up for any economic damage (thanks, Hurricane Harvey) the state dept. sanctions might have caused in the first place. So, Goldman S. was authorized to clean up the fucking mess by creating a \"\"rehypothecation event\"\" on Citgo's assets to which Russia will lack complete (legal) credibility. It really doesn't get any clearer or more obvious than this. Meanwhile, South American good will is eroding faster than Florida coastline during a global warming tipping point.\"", "title": "" }, { "docid": "498846", "text": "We are the most world's largest entertaining corporate events in Escape rooms. We have fabulous entertaining activities for our clients. Our so many clients are very happy after coming here. You can make the rememberable events here with our corporate events broward county. It is a unique opportunity for those people who want to make the special party in your budget and major events to entertainment. We are one of the finest service provider in USA. It is the most way to spend the vacation here.", "title": "" }, { "docid": "588877", "text": "FX is often purchased with leverage by both retail and wholesale speculators on the assumption daily movements are typically more restrained than a number of other asset classes. When volatility picks up unexpectedly these leveraged accounts can absolutely be wiped out. While these events are relatively rare, one happened as recently as 2016 when the Swiss National Bank unleashed the Swiss Franc from its Euro mooring. You can read about it here: http://www.reuters.com/article/us-swiss-snb-brokers-idUSKBN0KP1EH20150116", "title": "" } ]
PLAIN-1423	intelligence	[ { "docid": "MED-4949", "text": "Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.", "title": "Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain" }, { "docid": "MED-5141", "text": "Objective To examine the relation between IQ in childhood and vegetarianism in adulthood. Design Prospective cohort study in which IQ was assessed by tests of mental ability at age 10 years and vegetarianism by self-report at age 30 years. Setting Great Britain. Participants 8170 men and women aged 30 years participating in the 1970 British cohort study, a national birth cohort. Main outcome measures Self-reported vegetarianism and type of diet followed. Results 366 (4.5%) participants said they were vegetarian, although 123 (33.6%) admitted eating fish or chicken. Vegetarians were more likely to be female, to be of higher social class (both in childhood and currently), and to have attained higher academic or vocational qualifications, although these socioeconomic advantages were not reflected in their income. Higher IQ at age 10 years was associated with an increased likelihood of being vegetarian at age 30 (odds ratio for one standard deviation increase in childhood IQ score 1.38, 95% confidence interval 1.24 to 1.53). IQ remained a statistically significant predictor of being vegetarian as an adult after adjustment for social class (both in childhood and currently), academic or vocational qualifications, and sex (1.20, 1.06 to 1.36). Exclusion of those who said they were vegetarian but ate fish or chicken had little effect on the strength of this association. Conclusion Higher scores for IQ in childhood are associated with an increased likelihood of being a vegetarian as an adult.", "title": "IQ in childhood and vegetarianism in adulthood: 1970 British cohort study" }, { "docid": "MED-4939", "text": "Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.", "title": "Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis." }, { "docid": "MED-4941", "text": "Laboratory and population-based studies suggest that exposure to environmental toxicants may be one of several triggers for the development of endometriosis. We discuss evidence that modulation of the endometrial endocrine-immune interface could mechanistically link toxicant exposure to the development of this disease. Capsule Summary: Environmental toxicant exposure induces an inflammatory-like endometrial response that may promote the development of endometriosis.", "title": "Dioxin May Promote Inflammation-Related Development of Endometriosis" }, { "docid": "MED-5092", "text": "BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a \"gold standard\". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.", "title": "Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented in..." }, { "docid": "MED-4938", "text": "Objective To test the effect of four polychlorinated biphenyl congeners (PCB-77, PCB-105, PCB 153 and PCB 180) on expression of three adhesion markers, TGF-β1, VEGF, and type I collagen in normal human peritoneal and adhesion fibroblasts Design Cell culture study Settings University Research Laboratory Patients Primary cultures of normal peritoneal and adhesion fibroblasts were established from three patients. Interventions Fibroblasts were treated with PCB-77, PCB-105, PCB-153 or PCB-180, 20 ppm for 24 hours. Total RNA was extracted from each treatment and subjected to real-time RT/PCR. Main Outcome and Measures mRNA levels of type I collagen, VEGF and TGF-β1. Results Normal human peritoneal fibroblasts expressed type I collagen, VEGF and TGF-β1. Exposure of normal human fibroblasts to PCB-77, PCB-105, PCB-153 or PCB-180 did not affect mRNA levels of β-actin, the house keeping gene used to normalized RNA levels for the real-time RT/PCR, nor did it affect cell viability as assessed by trypan blue exclusion. PCB treatments, compared to control, resulted in no significant change for TGF-β1 or VEGF mRNA levels, in normal peritoneal and adhesion fibroblasts. In marked contrast, type I collagen mRNA levels were markedly increased in response to the brief 24 hrs exposure to each PCB, treatment each (P<0.0001) in both cell types. Conclusion The finding that PCB-77, PCB-105, PCB-153 or PCB-180 increased the expression of type I collagen in human normal peritoneal and adhesion fibroblasts is the first demonstration of involvement of organochlorines in the pathogenesis of tissue fibrosis. This may implicate organochlorine exposure as an etiologic factor in a wide variety of previously unlinked human ailments characterized by fibrosis.", "title": "PCBs Enhance Collagen I Expression from Human Peritoneal Fibroblasts" }, { "docid": "MED-5093", "text": "BACKGROUND: There are few studies reporting on docosahexaenoic acid (DHA, 22:6n-3) supplementation during pregnancy and infant cognitive function. DHA supplementation in pregnancy and infant problem solving in the first year have not been investigated. OBJECTIVE: We tested the hypothesis that infants born to women who consumed a DHA-containing functional food during pregnancy would demonstrate better problem-solving abilities and recognition memory than would infants born to women who consumed the placebo during pregnancy. DESIGN: In a double-blind, placebo-controlled, randomized trial, pregnant women consumed a DHA-containing functional food or a placebo from gestation week 24 until delivery. Study groups received DHA-containing cereal-based bars (300 mg DHA/92-kcal bar; average consumption: 5 bars/wk; n = 14) or cereal-based placebo bars (n = 15). The Infant Planning Test and Fagan Test of Infant Intelligence were administered to infants at age 9 mo. The problem-solving trial included a support step and a search step. The procedure was scored on the basis of the infant's performance on each step and on the entire problem (intention score and total intentional solutions). Scores were generated on the basis of the cumulative performance of the infant on 5 trials. RESULTS: Treatment had significant effects on the performance of problem-solving tasks: total intention score (P = 0.017), total intentional solutions (P = 0.011), and number of intentional solutions on both cloth (P = 0.008) and cover (P = 0.004) steps. There were no significant differences between groups in any measure of Fagan Test of Infant Intelligence. CONCLUSION: These data point to a benefit for problem solving but not for recognition memory at age 9 mo in infants of mothers who consumed a DHA-containing functional food during pregnancy.", "title": "Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but n..." }, { "docid": "MED-5091", "text": "BACKGROUND: Docosahexaenoic acid (DHA) is important to neural development. Whether DHA intakes are low enough in some pregnant women to impair infant development is uncertain. OBJECTIVE: We sought to determine whether DHA deficiency occurs in pregnant women and contributes to poor infant development. DESIGN: Biochemical cutoffs, dietary intakes, or developmental scores indicative of DHA deficiency are not defined. Infant development has a distribution in which an individual's potential development is unknown. This was a randomized intervention to establish a distribution of developmental scores for infants of women with DHA intakes considered to be above requirements against which to compare the development of infants of mothers consuming their usual diet. DHA (400 mg/d; n = 67) or a placebo (n = 68) was consumed by the women from 16 wk gestation until delivery. We determined maternal red blood cell ethanolamine phosphoglyceride fatty acids, dietary intakes at 16 and 36 wk gestation, and infant visual acuity at 60 d of age. RESULTS: We described an approach to identify DHA deficiency when biochemical and functional markers of deficiency are unknown. In multivariate analyses, infant visual acuity was related to sex (beta = 0.660, SE = 0.93, and odds ratio = 1.93) and maternal DHA intervention (beta = 1.215, SE = 1.64, and odds ratio = 3.37). More infant girls in the placebo than in the DHA intervention group had a visual acuity below average (P = 0.048). Maternal red blood cell ethanolamine phosphoglyceride docosatetraenoic acid was inversely related to visual acuity in boys (rho = -0.37, P < 0.05) and girls (rho = -0.48, P < 0.01). CONCLUSIONS: These studies suggest that some pregnant women in our study population were DHA-deficient.", "title": "Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants." }, { "docid": "MED-4942", "text": "The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.", "title": "Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey." }, { "docid": "MED-4948", "text": "The southeastern United States, and in particular the coastal areas along the Gulf of Mexico (Gulf Coast) in Florida, experience some of the highest levels of mercury deposition in the country. Although the State of Florida's coastal border is among the longest in the United States, and the State has issued fish consumption advisories due to mercury on multiple fish species, few data have been systematically collected to assess mercury levels in the human population of the state or to assess the efficacy of the consumption advisories. Because of the generally high rate of seafood consumption among coastal populations, the human population in the Florida Panhandle, near Pensacola, FL is potentially exposed to elevated levels of mercury. In the present study, we analyzed hair mercury levels in women of child-bearing age (16-49 years) who had resided near Pensacola, FL for at least 1 year. We also surveyed the fish consumption practices of the cohort and evaluated awareness of the Florida Fish Consumption Advisory. Hair mercury levels were significantly higher in women who consumed fish within the 30 days prior to sampling (p<0.05) and in those women who were unaware of the consumption advisory (p<0.05). Only 31% of the women reported knowledge of the consumption advisory and pregnant women exhibited lower awareness of the advisory than non-pregnant women. The data suggest that public health interventions such as education and fish advisories have not reached the majority of women in the counties surrounding Pensacola who are most at risk from consumption of fish with high levels of mercury.", "title": "Mercury levels and fish consumption practices in women of child-bearing age in the Florida Panhandle." }, { "docid": "MED-4622", "text": "We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.", "title": "A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States." }, { "docid": "MED-4940", "text": "Dioxins are known to affect infant growth and neurodevelopment in both humans and animals. In this study, we examined the relationship between neonatal head circumference, which is related to fetal brain development, and the concentration of dioxins in breast milk as an indicator of maternal exposure. A total of 42 milk samples were obtained on the fifth to eighth postpartum day from mothers in Japan exposed to dioxins in the environment. The levels of seven dioxins and 10 furan isomers were measured in each milk sample using an HR-GC/MS system. The relationships between the concentration of each dioxin isomer and newborn size, including head circumference, were then investigated after adjustment for confounding factors. The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin isomer, negatively correlated with newborn head circumference, even after adjustment for gestational age, infant sex, parity and other confounding factors. However, there were no significant relationships between the concentration of other dioxin and furan isomers in maternal breast milk and infant height, weight and chest circumference at birth. These facts suggested that fetal brain development might be influenced by maternal exposure to TCDD in the environment.", "title": "2,3,7,8-Tetrachlorodibenzo-p-dioxin in maternal breast milk and newborn head circumference." }, { "docid": "MED-4947", "text": "The focus of the present study was on the relationship between Hong Kong male subfertility and fish consumption. Mercury concentrations found in the hair of 159 Hong Kong males aged 25-72 (mean age = 37 years) was positively correlated with age and was significantly higher in Hong Kong subjects than in European and Finnish subjects (1.2 and 2.1 ppm, respectively). Mercury in the hair of 117 subfertile Hong Kong males (4.5 ppm, P < 0.05) was significantly higher than mercury levels found in hair collected from 42 fertile Hong Kong males (3.9 ppm). Subfertile males had approx. 40% more mercury in their hair than fertile males of similar age. Although there were only 35 female subjects, they had significantly lower levels of hair mercury than males in similar age groups. Overall, males had mercury levels that were 60% higher than females. Hair samples collected from 16 vegetarians living in Hong Kong (vegans that had consumed no fish, shellfish or meat for at least the last 5 years) had very low levels of mercury. Their mean hair mercury concentration was only 0.38 ppm.", "title": "Hong Kong male subfertility links to mercury in human hair and fish." } ]	[ { "docid": "MED-1166", "text": "Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development. Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children. Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment. Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores. Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.", "title": "Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children" }, { "docid": "MED-2904", "text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.", "title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data" }, { "docid": "MED-3026", "text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.", "title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data" }, { "docid": "MED-1681", "text": "BACKGROUND: Previous studies have examined individual dietary and lifestyle factors in relation to type 2 diabetes, but the combined effects of these factors are largely unknown. METHODS: We followed 84,941 female nurses from 1980 to 1996; these women were free of diagnosed cardiovascular disease, diabetes, and cancer at base line. Information about their diet and lifestyle was updated periodically. A low-risk group was defined according to a combination of five variables: a bodymass index (the weight in kilograms divided by the square of the height in meters) of less than 25; a diet high in cereal fiber and polyunsaturated fat and low in trans fat and glycemic load (which reflects the effect of diet on the blood glucose level); engagement in moderate-to-vigorous physical activity for at least half an hour per day; no current smoking; and the consumption of an average of at least half a drink of an alcoholic beverage per day. RESULTS: During 16 years of follow-up, we documented 3300 new cases of type 2 diabetes. Overweight or obesity was the single most important predictor of diabetes. Lack of exercise, a poor diet, current smoking, and abstinence from alcohol use were all associated with a significantly increased risk of diabetes, even after adjustment for the body-mass index. As compared with the rest of the cohort, women in the low-risk group (3.4 percent of the women) had a relative risk of diabetes of 0.09 (95 percent confidence interval, 0.05 to 0.17). A total of 91 percent of the cases of diabetes in this cohort (95 percent confidence interval, 83 to 95) could be attributed to habits and forms of behavior that did not conform to the low-risk pattern. CONCLUSIONS: Our findings support the hypothesis that the vast majority of cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle.", "title": "Diet, lifestyle, and the risk of type 2 diabetes mellitus in women." }, { "docid": "MED-5325", "text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.", "title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)" }, { "docid": "MED-2723", "text": "Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations--the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492,000-669,000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Health and economic burden of the projected obesity trends in the USA and the UK." }, { "docid": "MED-4436", "text": "The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.", "title": "Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition." }, { "docid": "MED-2844", "text": "OBJECTIVE It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic β-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM. RESEARCH DESIGN AND METHODS A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors. RESULTS Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87–1.43), 1.31 (1.03–1.68), 1.51 (1.17–1.93), and 1.58 (1.21–2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10–1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk. CONCLUSIONS These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.", "title": "A Prospective Study of Prepregnancy Dietary Iron Intake and Risk for Gestational Diabetes Mellitus" }, { "docid": "MED-5006", "text": "We projected future prevalence and BMI distribution based on national survey data (National Health and Nutrition Examination Study) collected between 1970s and 2004. Future obesity-related health-care costs for adults were estimated using projected prevalence, Census population projections, and published national estimates of per capita excess health-care costs of obesity/overweight. The objective was to illustrate potential burden of obesity prevalence and health-care costs of obesity and overweight in the United States that would occur if current trends continue. Overweight and obesity prevalence have increased steadily among all US population groups, but with notable differences between groups in annual increase rates. The increase (percentage points) in obesity and overweight in adults was faster than in children (0.77 vs. 0.46-0.49), and in women than in men (0.91 vs. 0.65). If these trends continue, by 2030, 86.3% adults will be overweight or obese; and 51.1%, obese. Black women (96.9%) and Mexican-American men (91.1%) would be the most affected. By 2048, all American adults would become overweight or obese, while black women will reach that state by 2034. In children, the prevalence of overweight (BMI >/= 95th percentile, 30%) will nearly double by 2030. Total health-care costs attributable to obesity/overweight would double every decade to 860.7-956.9 billion US dollars by 2030, accounting for 16-18% of total US health-care costs. We continue to move away from the Healthy People 2010 objectives. Timely, dramatic, and effective development and implementation of corrective programs/policies are needed to avoid the otherwise inevitable health and societal consequences implied by our projections .", "title": "Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic." }, { "docid": "MED-4051", "text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients." }, { "docid": "MED-1331", "text": "Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored.", "title": "Dynamics of the nutrition transition toward the animal foods sector in China and its implications: a worried perspective." }, { "docid": "MED-2673", "text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.", "title": "Determination of microbial transglutaminase in meat and meat products." }, { "docid": "MED-4239", "text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.", "title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro." }, { "docid": "MED-2248", "text": "The consequences of a change from a mixed to a lactovegetarian diet for 12 mo on trace element concentrations in plasma, hair, urine, and feces were studied in 16 women and 4 men. After the diet shift, intakes of zinc and magnesium did not change but that of selenium decreased by 40%. Three months after the diet shift, plasma and hair concentrations of zinc, copper, and selenium had decreased but those of magnesium had increased and the concentrations of mercury, lead, and cadmium in hair were lower. Also, the excretion of zinc, copper, and magnesium in urine, and that of selenium in urine and feces had decreased. Only small changes occurred during the remaining lactovegetarian-diet period. Three years later trace element concentrations had reverted towards baseline concentrations; copper values were similar to baseline concentrations but data for magnesium were slightly higher, and more complex patterns were observed for zinc and selenium. It is concluded that a shift to a lactovegetarian diet changes trace element status.", "title": "Trace element status in healthy subjects switching from a mixed to a lactovegetarian diet for 12 mo." }, { "docid": "MED-4073", "text": "The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces tumours of the breast, colon and prostate in rats. Here we show that in addition to its well-established genotoxicity, which can be detected at concentrations >10(-6) M, PhIP is also oestrogenic. In COS-1 cells transiently transfected with an oestrogen-responsive reporter gene, PhIP (10(-10)-10(-6) M) mediated transcription through oestrogen receptor (ER) alpha, but not ER-beta, and inhibition by the pure ER antagonist ICI 182 780 demonstrated a requirement for a functional ER. In contrast, the structurally related food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) failed to induce reporter gene transcription. Additionally, we show that in a hormonally responsive breast cancer cell line (MCF-7 cells), PhIP induced transcriptional activation using endogenously expressed ER. Examination of the genotoxic potential of PhIP using a model mammalian cell mutation assay (hprt(-) locus) demonstrated that the genetic toxicology of PhIP was readily detectable, but separate, in terms of effective concentration, from its oestrogenic activity. To determine whether the oestrogenicity of PhIP could mediate oestrogen-dependent responses such as cell growth, we examined the growth of hormonally responsive cells (MCF-7 cells). We show that PhIP can stimulate cell proliferation and, again, this was dependent upon a functional ER. Using ligand blotting, we further show that PhIP can stimulate the expression of progesterone receptor (PR-A and PR-B) and c-MYC and activate the MAPK signal transduction pathway. These responses were similar to that produced by oestradiol, in terms of temporal aspects, potency and a requirement for a functional ER. Each of these dose-dependent mitogenic responses occurred at concentrations of PhIP ( approximately 10(-9)-10(-11)M) that are likely to be equivalent to systemic human exposure via consumption of cooked meat. Thus PhIP can induce cellular responses that encompass altered gene expression and mitogenesis. We suggest that the combination of genetic toxicology and oestrogen-like promotion of genomic and cellular events provide a mechanism for the tissue-specific tumorigenicity of this compound.", "title": "The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-speci..." }, { "docid": "MED-4197", "text": "Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.", "title": "Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation." }, { "docid": "MED-4000", "text": "Coconut oil is a common edible oil in many countries, and there is mixed evidence for its effects on lipid profiles and cardiovascular disease risk. Here we examine the association between coconut oil consumption and lipid profiles in a cohort of 1,839 Filipino women (age 35–69 years) participating in the Cebu Longitudinal Health and Nutrition Survey, a community based study in Metropolitan Cebu City. Coconut oil intake was measured as individual coconut oil intake calculated using two 24-hour dietary recalls (9.54 ± 8.92 grams). Cholesterol profiles were measured in plasma samples collected after an overnight fast. Mean lipid values in this sample were total cholesterol (TC) (186.52 ± 38.86 mg/dL), high density lipoprotein cholesterol (HDL-c) (40.85 ± 10.30 mg/dL), low density lipoprotein cholesterol (LDL-c) (119.42 ± 33.21 mg/dL), triglycerides (130.75 ± 85.29 mg/dL) and the TC/HDL ratio (4.80 ± 1.41). Linear regression models were used to estimate the association between coconut oil intake and each plasma lipid outcome after adjusting for total energy intake, age, body mass index (BMI), number of pregnancies, education, menopausal status, household assets and urban residency. Dietary coconut oil intake was positively associated with HDL-c levels.", "title": "Coconut oil predicts a beneficial lipid profile in pre-menopausal women in the Philippines" }, { "docid": "MED-1621", "text": "Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.", "title": "Coffee, tea, and mortality." }, { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-3563", "text": "In developing countries like India, occurrence of Human papillomavirus (HPV) in cervical cancer as well as in the asymptomatic population was observed to be very high. Studies on HPV prevalence have been conducted in different parts of the country but no data were available from the eastern region of Uttar Pradesh (UP). The present study aimed to determine the status of HPV prevalence and its association with different socio-demographic factors in this population. Prevalence of HPV was investigated in a total of 2424 cervical scrape samples of asymptomatic women. Primer sets from L1 consensus region of viral genome were used to detect the presence of HPV, and the positive samples were genotyped by sequencing. Univariate binary logistic regression analysis was used to evaluate association of socio-demographic factors with HPV. 9.9% of the clinically asymptomatic women were found to be infected with HPV comprising 26 different genotypes. Among HPV-positive women, 80.8% showed single infection, while 15.4% harboured multiple infections. HPV-16 (63.7%) was the most prevalent, followed by HPV-31 (6.7%), HPV-6 (5.4%), HPV-81 (4.6%) and HPV-33 (4.2%). Significant association of HPV with non-vegetarian diet (P less than 0.05) and rural residential areas (P less than 0.01) were observed. High prevalence of HPV-16 in asymptomatic women of this population, a frequency comparable to invasive cervical cancers, highlights an urgent need for a therapeutic HPV vaccine covering HPV-16 and other high-risk types to provide protection against the disease.", "title": "High prevalence of oncogenic HPV-16 in cervical smears of asymptomatic women of eastern Uttar Pradesh, India: a population-based study." }, { "docid": "MED-5064", "text": "To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.", "title": "Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative ..." }, { "docid": "MED-4412", "text": "BACKGROUND & AIMS: The aim of this study was to investigate whether nutritional risk factors, especially black tea consumptions, are inversely associated with the development of chronic obstructive pulmonary disease (COPD) in male smokers. METHODS: Forty male smokers with clinical diagnosis of COPD (Group-I (GI)) and 36 healthy smokers without COPD (Group-II (GII)) were included in this study. We compared the dietary habits and food intakes of the two groups using an adaptation of the Arizona Food Frequency Questionnaire (AFFQ). Question form included a list of 65 food items formed from five main food groups (grain, meat and alternatives, dairy products, vegetables-fruits and fat) and 25 dietary habits. The data were evaluated by binary logistic regression analysis, receiver operating characteristic (ROC) curve, Kolmogorov-Smirnov, Student's t, Mann-Whitney, and Chi-square tests. RESULTS: When both groups compared, black tea consumptions (GI-700ml; GII-1600ml (OR: 0.635, P<0.001)), vegetable fruits scores (GI-54.30; GII-63.81 (OR: 0.863, P<0.001)), regularly breakfast habit (GI-24 patients; GII-36 cases (OR: 0.549, P<0.001)) and eating salty (GI-22 patients; GII-5 cases (P<0.001)) made significant differences. In ROC curves, the area under the curve of black tea (0.898 (95% CI: 0.819-0.977) and vegetables-fruits (0.833 (95% CI: 0.727-0.938) provided high accuracy to distinguish between COPD group and controls (P<0.001). CONCLUSIONS: High intakes of black tea and vegetables-fruits consumptions may be protecting male smokers from developing COPD.", "title": "Nutritional risk factors for the development of chronic obstructive pulmonary disease (COPD) in male smokers." }, { "docid": "MED-857", "text": "Individual-based studies that investigated the relation between dietary alpha-linolenic acid (ALA) intake and prostate cancer risk have shown inconsistent results. We carried out a meta-analysis of prospective studies to examine this association. We systematically searched studies published up to December 2008. Log relative risks (RRs) were weighted by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). We identified five prospective studies that met our inclusion criteria and reported risk estimates by categories of ALA intake. Comparing the highest to the lowest ALA intake category, the pooled RR was 0.97 (95% CI:0.86-1.10) but the association was heterogeneous. Using the reported numbers of cases and non-cases in each category of ALA intake, we found that subjects who consumed more than 1.5 g/day of ALA compared with subjects who consumed less than 1.5 g/day had a significant decreased risk of prostate cancer: RR = 0.95 (95% CI:0.91-0.99). Divergences in results could partly be explained by differences in sample sizes and adjustment but they also highlight limits in dietary ALA assessment in such prospective studies. Our findings support a weak protective association between dietary ALA intake and prostate cancer risk but further research is needed to conclude on this question.", "title": "Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis." }, { "docid": "MED-1042", "text": "The human colon is still a relatively unknown viscus, especially concerning its motor activity. However, in recent years, techniques have been perfected that allow a better understanding of colonic motility, especially through prolonged recording periods. In this way, it has been demonstrated that the viscus contracts according to a circadian trend, is responsive to physiological stimuli (meals, sleep), and features high amplitude, propulsive contractions that are part of the complex dynamic of the defecatory process. These physiological properties and their alterations in patients with chronic idiopathic constipation are reviewed in this article.", "title": "Colonic motility in man: features in normal subjects and in patients with chronic idiopathic constipation." }, { "docid": "MED-5224", "text": "Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.", "title": "Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye" }, { "docid": "MED-3129", "text": "BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.", "title": "BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression." }, { "docid": "MED-4482", "text": "Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer.", "title": "Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer" }, { "docid": "MED-3809", "text": "Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract." }, { "docid": "MED-3052", "text": "Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.", "title": "Obesity and addiction: neurobiological overlaps." }, { "docid": "MED-1705", "text": "Despite an archive of over 73,000 research papers published in the last two decades on the subject of Alzheimer's disease (AD), little clinical progress has been made relative to how people get sporadic AD and what can be done to help them avoid it. This review spotlights strategic steps that could be a turning point in the dramatic lowering of Alzheimer prevalence. The main strategy includes application of four pillars of prevention: 1) early identification of AD vascular risk factors; 2) early detection of AD vascular risk factors; 3) early intervention of AD vascular risk factors based on evidence-based medical decisions; 4) patient follow-up to assess and modify interventions as needed. Tandem to these four pillars of prevention, a proactive lifestyle consisting of a healthy diet coupled to physical and mental activity should be applied as part of any therapeutic intervention. We are persuaded by mounting and compelling evidence that AD is a multifactorial disorder kindled by vascular risk factors that generate chronic brain hypoperfusion (CBH) during advanced aging. A pathobiological cascade of biochemical events in the presence of CBH that leads to oxidative stress and neurodegeneration appears to involve multiple biofactors including micronutrients, trace metals, lipids, and pro-oxidants, as reviewed in this special issue of BioFactors. Modulation of these biofactors may help prevent or control incipient AD. © 2012 International Union of Biochemistry and Molecular Biology, Inc. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "A turning point for Alzheimer's disease?" } ]
PLAIN-253	Diet vs. Exercise: What’s More Important?	[ { "docid": "MED-4286", "text": "Nuts are rich sources of multiple nutrients and phytochemicals associated with health benefits, including reduced cardiovascular disease risk. This has prompted recommendations to increase their consumption. However, they are also high in fat and are energy dense. The associations between these properties, positive energy balance and body weight raise questions about such recommendations. Numerous epidemiological and clinical studies show that nuts are not associated with weight gain. Mechanistic studies indicate this is largely attributable to the high satiety and low metabolizable energy (poor bioaccessibility leading to inefficient energy absorption) properties of nuts. Compensatory dietary responses account for 55-75% of the energy provided by nuts. Limited data suggest that routine nut consumption is associated with elevated resting energy expenditure and the thermogenic effect of feeding, resulting in dissipation of another portion of the energy they provide. Additionally, trials contrasting weight loss through regimens that include or exclude nuts indicate improved compliance and greater weight loss when nuts are permitted. Nuts may be included in the diet, in moderation, to enhance palatability, nutrient quality, and chronic disease risk reduction without compromising weight loss or maintenance.", "title": "Nuts and healthy body weight maintenance mechanisms." }, { "docid": "MED-5327", "text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.", "title": "The association between dietary patterns and mental health in early adolescence." }, { "docid": "MED-4257", "text": "We conducted a systematic review investigating body fat distribution in older adults and its association with morbidity and mortality. Our search yielded 2,702 citations. Following three levels of screening, 25 studies were selected to evaluate the association between body fat distribution and comorbidity, and 17 studies were used in the mortality analysis. Most of the selected studies in our analyses used anthropometric measures, e.g., body mass index (BMI), waist circumference, and waist-hip ratio; relatively few studies used direct measures, such as body fat/lean mass, and percentage body fat. Studies reported inconsistent findings regarding the strongest predictor(s) of morbidity and mortality. However, the majority of studies suggested that BMI per se was not the most appropriate predictor of morbidity and mortality in the elderly because of its inability to discern or detect age-related body fat redistribution. In addition, studies using BMI found that the optimal BMI range for the lowest mortality in the elderly was overweight (25 kg/m2 ≤ BMI < 30 kg/m2) or mildly obese (30 kg/m2 ≤ BMI < 35 kg/m2). Our findings suggest that the current clinical guidelines, recommending that overweight and obesity are major risk factors for increased morbidity and mortality are not applicable to this population. Therefore, the central message of this review is to admonish the government to establish new guidelines specifically for this population, using a combination of body fat distribution measurements, and to certify that these guidelines will not be applied to inappropriate populations.", "title": "A Systematic Review of Body Fat Distribution and Mortality in Older People" }, { "docid": "MED-5341", "text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.", "title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro." }, { "docid": "MED-5339", "text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.", "title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat." }, { "docid": "MED-4256", "text": "This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.", "title": "A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0·5 could be a suitable..." }, { "docid": "MED-5335", "text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.", "title": "Does a vegan diet reduce risk for Parkinson's disease?" }, { "docid": "MED-5322", "text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.", "title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting." }, { "docid": "MED-5324", "text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.", "title": "Effects of a high-fat meal on pulmonary function in healthy subjects." }, { "docid": "MED-4686", "text": "There is ample reason to believe that diets rich in phytochemicals provide protection from vascular diseases and many cancers; direct antioxidant activity as well as modulation of enzyme expression or hormone activity contribute to this effect. Phytochemicals derived from diverse foods presumably can interact additively and (possibly) synergistically; thus, the total dietary load of phytochemicals may have important implications for health. As a means of very roughly quantifying this load, a \"phytochemical index\" (PI) is proposed, defined as the percent of dietary calories derived from foods rich in phytochemicals. Calories derived from fruits, vegetables (excluding potatoes), legumes, whole grains, nuts, seeds, fruit/vegetable juices, soy products, wine, beer, and cider - and foods compounded therefrom - would be counted in this index. Partial credit could be given for antioxidant-rich extra virgin olive oil. Other added oils, refined sugars, refined grains, potato products, hard liquors, and animal products - regrettably, the chief sources of calories in typical Western diets - would be excluded. Although the PI would provide only a very rough approximation of the quantity or quality of phytochemical nutrition, it nonetheless could aid epidemiologists in exploring the health consequences of diets high in phytochemical-rich plant foods, and could also help clinical nutritionists in their efforts to improve the phytochemical nutrition of their clients.", "title": "Proposal for a dietary \"phytochemical index\"." }, { "docid": "MED-5342", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-4261", "text": "BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.", "title": "Meat consumption and prospective weight change in participants of the EPIC-PANACEA study." }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-5330", "text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.", "title": "Effect of a single high-fat meal on endothelial function in healthy subjects." }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-5325", "text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.", "title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)" }, { "docid": "MED-5328", "text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.", "title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2" }, { "docid": "MED-5323", "text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.", "title": "Endocrine-disrupting chemicals and obesity development in humans: a review." }, { "docid": "MED-5331", "text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.", "title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland." }, { "docid": "MED-5340", "text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.", "title": "Renal function parameters of Thai vegans compared with non-vegans." }, { "docid": "MED-5333", "text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.", "title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis." }, { "docid": "MED-5332", "text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.", "title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age." }, { "docid": "MED-5334", "text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.", "title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study." }, { "docid": "MED-5326", "text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?" }, { "docid": "MED-5338", "text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.", "title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease" }, { "docid": "MED-5329", "text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.", "title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet." } ]	[ { "docid": "MED-1543", "text": "The goal of this research was to evaluate the personal health behaviors of physicians in training and attending physicians in association with patient-related lifestyle counseling. Physicians at a major teaching hospital were surveyed regarding their personal lifestyle behavior, perceived confidence, and frequency of counseling patients regarding lifestyle behaviors. One hundred eighty-three total responses were received. Trainees were more likely to consume fast food and less likely to consume fruits and vegetables than attendings. Attending physicians were more likely to exercise 4 or more days per week and more than 150 minutes per week. Attending physicians were more likely to counsel their patients regarding a healthy diet (70.7% vs 36.3%, P<.0001) and regular exercise (69.1% vs 38.2%, P<.0001) compared with trainees. Few trainees or attendings were confident in their ability to change patients' behaviors. Predictors of confidence in counseling for exercise included the provider's own exercise time of > 150 minutes per week, being overweight, and reported adequate training in counseling. Only adequate training in counseling was a predictor of strong self-efficacy for counseling in diet. Many physicians lack confidence in their ability to counsel patients regarding lifestyle. Personal behaviors including regular exercise and better training in counseling techniques may improve patient counseling. © 2010 Wiley Periodicals, Inc.", "title": "Patient-related diet and exercise counseling: do providers' own lifestyle habits matter?" }, { "docid": "MED-1053", "text": "CONTEXT: While some studies have shown that physicians with healthy personal habits are especially likely to discuss prevention with their patients, to our knowledge no one has published information testing whether physician credibility and patient motivation to adopt healthier habits are enhanced by physician's disclosures of their own healthy behaviors. DESIGN: Two brief health education videos about improving diet and exercise were produced and shown to subjects (n1 = 66, n2 = 65) in an Emory University general medical clinic waiting room in Atlanta, Ga. In one video, the physician revealed an additional half minute of information about her personal healthy dietary and exercise practices and had a bike helmet and an apple visible on her desk (physician-disclosure video). In the other video, discussion of personal practices and the apple and bike helmet were not included (control video). RESULTS: Viewers of the physician-disclosure video considered the physician to be generally healthier, some-what more believable, and more motivating than did viewers of the control video. They also rated this physician to be specifically more believable and motivating regarding exercise and diet (P < or = .001). CONCLUSION: Physicians' abilities to motivate patients to adopt healthy habits can be enhanced by conveying their own healthy habits. Educational institutions should consider encouraging health professionals-in-training to practice and demonstrate healthy personal lifestyles.", "title": "Physician disclosure of healthy personal behaviors improves credibility and ability to motivate." }, { "docid": "MED-3815", "text": "Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.", "title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes" }, { "docid": "MED-5225", "text": "Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.", "title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes" }, { "docid": "MED-1488", "text": "Aims To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. Methods This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected. Results Participants required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously. Conclusions People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients’ expectations and informing individual patient decisions.", "title": "What benefit do patients expect from adding second and third antihypertensive drugs?" }, { "docid": "MED-944", "text": "Many products used in everyday life are made with the assistance of nanotechnologies. Cosmetic, pharmaceuticals, sunscreen, powdered food are only few examples of end products containing nano-sized particles (NPs), generally added to improve the product quality. To evaluate correctly benefits vs. risks of engineered nanomaterials and consequently to legislate in favor of consumer's protection, it is necessary to know the hazards connected with the exposure levels. This information implies transversal studies and a number of different competences. On analytical point of view the identification, quantification and characterization of NPs in food matrices and in cosmetic or personal care products pose significant challenges, because NPs are usually present at low concentration levels and the matrices, in which they are dispersed, are complexes and often incompatible with analytical instruments that would be required for their detection and characterization. This paper focused on some analytical techniques suitable for the detection, characterization and quantification of NPs in food and cosmetics products, reports their recent application in characterizing specific metal and metal-oxide NPs in these two important industrial and market sectors. The need of a characterization of the NPs as much as possible complete, matching complementary information about different metrics, possible achieved through validate procedures, is what clearly emerges from this research. More work should be done to produce standardized materials and to set-up methodologies to determine number-based size distributions and to get quantitative date about the NPs in such a complex matrices.", "title": "Nanomaterials in consumer products: a challenging analytical problem." }, { "docid": "MED-2300", "text": "Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to \"successful aging\". In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Exercise and longevity." }, { "docid": "MED-3156", "text": "Exercise-induced oxidative stress is instrumental in achieving the health benefits from regular exercise. Therefore, inappropriate use of fruit-derived products (commonly applied as prophalytic antioxidants) may counteract the positive effects of exercise. Using human exercise and cellular models we found that 1) blackcurrant supplementation suppressed exercise-induced oxidative stress, e.g., plasma carbonyls (0.9 +/- 0.1 vs. 0.6 +/- 0.1 nmol/mg protein, placebo vs. blackcurrant), and 2) preincubation of THP-1 cells with an anthocyanin-rich blackcurrant extract inhibited LPS-stimulated cytokine secretion [TNF-alpha (16,453 +/- 322 vs. 10,941 +/- 82 pg/ml, control vs. extract, P < 0.05) and IL-6 (476 +/- 14 vs. 326 +/- 32 pg/ml, control vs. extract, P < 0.05)] and NF-kappaB activation. In addition to its antioxidant and anti-inflammatory properties, we found that postexercise plasma collected after blackcurrant supplementation enhanced the differential temporal LPS-stimulated inflammatory response in THP-1 cells, resulting in an early suppression of TNF-alpha (1,741 +/- 32 vs. 1,312 +/- 42 pg/ml, placebo vs. blackcurrant, P < 0.05) and IL-6 (44 +/- 5 vs. 36 +/- 3 pg/ml, placebo vs. blackcurrant, P < 0.05) secretion after 24 h. Furthermore, by using an oxidative stress cell model, we found that preincubation of THP-1 cells with hydrogen peroxide (H(2)O(2)) prior to extract exposure caused a greater suppression of LPS-stimulated cytokine secretion after 24 h, which was not evident when cells were simultaneously incubated with H(2)O(2) and the extract. In summary, our findings support the concept that consumption of blackcurrant anthocyanins alleviate oxidative stress, and may, if given at the appropriate amount and time, complement the ability of exercise to enhance immune responsiveness to potential pathogens.", "title": "Short-term blackcurrant extract consumption modulates exercise-induced oxidative stress and lipopolysaccharide-stimulated inflammatory responses." }, { "docid": "MED-748", "text": "Questions of medical ethics are often treated as especially difficult casuistical problems or as difficult cases illustrative of paradoxes or advantages in global moral theories. I argue here, in opposition to such approaches, for the inseparability of questions of social history and social theory from any normative assessment of medical practices. The focus of the discussion is the question of the legitimacy of the social authority exercised by physicians, and the insufficiency of traditional defences of such authority in liberal societies (voluntarist, informed consent approaches), as well as traditional attacks on such strategies (ideology critique). Seeing such authority as institution bound and role based, it is argued, can help reframe, more broadly and more adequately, what is an \"ethical problem\" in medical practice and why.", "title": "Medical practice and social authority." }, { "docid": "MED-1467", "text": "Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the \"culprits\" were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount. Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties. Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance. There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear. Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.", "title": "Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots." }, { "docid": "MED-1520", "text": "Background Enhancing athletic performance is a great desire among the athletes, coaches and researchers. Mint is one of the most famous natural herbs used for its analgesic, anti-inflammatory, antispasmodic, antioxidant, and vasoconstrictor effects. Even though inhaling mint aroma in athletes has been investigated, there were no significant effects on the exercise performance. Methods Twelve healthy male students every day consumed one 500 ml bottle of mineral water, containing 0.05 ml peppermint essential oil for ten days. Blood pressure, heart rate, and spirometry parameters including forced vital capacity (FVC), peak expiratory flow rate (PEF), and peak inspiratory flow (PIF) were determined one day before, and after the supplementation period. Participants underwent a treadmill-based exercise test with metabolic gas analysis and ventilation measurement using the Bruce protocol. Results The FVC (4.57 ± 0.90 vs. 4.79 ± 0.84; p < 0.001), PEF (8.50 ± 0.94 vs. 8.87 ± 0.92; p < 0.01), and PIF (5.71 ± 1.16 vs. 6.58 ±1.08; p < 0.005) significantly changed after ten days of supplementation. Exercise performance evaluated by time to exhaustion (664.5 ± 114.2 vs. 830.2 ± 129.8 s), work (78.34 ±32.84 vs. 118.7 ± 47.38 KJ), and power (114.3 ± 24.24 vs. 139.4 ± 27.80 KW) significantly increased (p < 0.001). In addition, the results of respiratory gas analysis exhibited significant differences in VO2 (2.74 ± 0.40 vs. 3.03 ± 0.351 L/min; p < 0.001), and VCO2 (3.08 ± 0.47 vs. 3.73 ± 0.518 L/min; p < 0.001). Conclusions The results of the experiment support the effectiveness of peppermint essential oil on the exercise performance, gas analysis, spirometry parameters, blood pressure, and respiratory rate in the young male students. Relaxation of bronchial smooth muscles, increase in the ventilation and brain oxygen concentration, and decrease in the blood lactate level are the most plausible explanations.", "title": "The effects of peppermint on exercise performance" }, { "docid": "MED-4640", "text": "BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be \"improved\". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.", "title": "PASSCLAIM--gut health and immunity." }, { "docid": "MED-4452", "text": "Background: Evidence for the role of diet and physical activity in cancer incidence is well documented, but owing to increased cancer survivorship, an understanding of these lifestyle factors after a cancer diagnosis is of crucial importance. The purpose of this review was to update the literature in a review undertaken for the National Cancer Survivorship Initiative and to include observational studies that were not included in the WCRF survivorship systematic review. Methods: Evidence was initially gathered from pre-defined searches of the Cochrane Library Database and PubMed from March 2006 to February 2010. After a comprehensive review regarding lifestyle and cancer, for the purpose of this article, any studies not related to diet and physical activity, prognostic outcomes, and breast, colorectal or prostate cancers were excluded. Another search of 2011 literature was conducted to update the evidence. Results: A total of 43 records were included in this review. Evidence from observational studies suggests that a low-fat, high-fibre diet might be protective against cancer recurrence and progression. However, there is a paucity of RCTs substantiating this. There is more support for physical activity, with a dose response for better outcomes. When synthesized with findings from the World Cancer Research Fund review of RCTs investigating the effect of diet and physical activity interventions on cancer survival, evidence suggests that the mechanism of benefit from diet and physical activity pertains to body weight, with excess body weight being a risk factor, which is modifiable through lifestyle. Implications: Cancer survivors would like to have a more active role in their health care and to know how to look after themselves after diagnosis, including what diet and lifestyle changes they should make. The challenge is in integrating lifestyle support into standardised models of aftercare.", "title": "The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature" }, { "docid": "MED-834", "text": "Polycystic ovarian syndrome (PCOS) affects 18–22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966–April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39 IU/l (95% CI 0.09 to 0.70, P=0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37 nmol/l (95% CI 1.27 to 3.47, P<0.0001), total testosterone levels, MD −0.13 nmol/l (95% CI −0.22 to −0.03, P=0.008), androstenedione levels, MD −0.09 ng/dl (95% CI −0.15 to −0.03, P=0.005), free androgen index (FAI) levels, MD −1.64 (95% CI −2.94 to −0.35, P=0.01) and Ferriman–Gallwey (FG) score, MD −1.01 (95% CI −1.54 to −0.48, P=0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42 IU/l (95% CI 0.11 to 0.73, P=0.009), SHBG levels, MD 3.42 nmol/l (95% CI 0.11 to 6.73, P=0.04), total testosterone levels, MD −0.16 nmol/l (95% CI −0.29 to −0.04, P=0.01), androstenedione levels, MD −0.09 ng/dl (95% CI −0.16 to −0.03, P=0.004) and FG score, MD −1.13 (95% CI −1.88 to −0.38, P=0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS.", "title": "Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis" }, { "docid": "MED-1641", "text": "Background Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). Methodology/Principal Findings MBF was measured with 15O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58±13 years) and in CAD patients (n = 15, mean age 61±9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26±0.56 vs. 2.02±0.56, P<0.005), remote (2.40±0.70 vs. 1.78±0.46, P<0.001) and in stenotic segments (1.90±0.41 vs. 1.38±0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). Conclusions We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls.", "title": "Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls" }, { "docid": "MED-4269", "text": "PURPOSE OF REVIEW: High-fiber diets have been shown to reduce plasma concentrations of inflammation markers. Increased production of fermentation-derived short-chain fatty acids (SCFAs) is one of the factors that could exert these positive effects. This review examines the effects of SCFAs on immune cells and discusses the relevance of their effects on systemic inflammation, as frequently seen in obesity. RECENT FINDINGS: SCFAs have been shown to reduce chemotaxis and cell adhesion; this effect is dependent on type and concentration of SCFA. In spite of conflicting results, especially butyrate seems to have an anti-inflammatory effect, mediated by signaling pathways like nuclear factor-κB and inhibition of histone deacetylase. The discrepancies in the results could be explained by differences in cell types used and their proliferative and differentiation status. SUMMARY: SCFAs show anti-inflammatory effects and seem to have the potency to prevent infiltration of immune cells from the bloodstream in, for example, the adipose tissue. In addition, their ability to inhibit the proliferation and activation of T cells and to prevent adhesion of antigen-presenting cells could be important as it recently has been shown that obesity-associated inflammation might be antigen-dependent. More studies with concentrations in micromolar range are needed to approach more physiological concentrations.", "title": "Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health?" }, { "docid": "MED-3894", "text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.", "title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling." }, { "docid": "MED-2584", "text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.", "title": "Dietary risk factors for colon cancer in a low-risk population." }, { "docid": "MED-4890", "text": "Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.", "title": "Effect of diet and exercise intervention on the growth of prostate epithelial cells." }, { "docid": "MED-2166", "text": "Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors are likely to play important etiological roles. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. Previously, elevated blood harmane concentrations were demonstrated in ET cases compared to controls, but these observations were all been cross-sectional, assessing each subject at only one time point. Thus, no one has ever repeat-assayed blood harmane in the same subjects twice. Whether the observed case-control difference persists at a second time point, years later, is unknown. The current goal was to re-assess a sample of our ET cases and controls to determine whether blood harmane concentration remained elevated in ET at a second time point. Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method in 63 ET cases and 70 controls. A mean of approximately 6 years elapsed between the initial and this subsequent blood harmane determination. The mean log blood harmane concentration was significantly higher in cases than controls (0.30 ± 0.61 g−10/ml vs. 0.08 ± 0.55 g−10/ml), and the median value in cases was double that of controls: 0.22 g−10/ml vs. 0.11 g−10/ml. The log blood harmane concentration was highest in cases with a family history of ET. Blood harmane concentration was elevated in ET cases compared to controls when re-assessed at a second time point several years later, indicating what seems to be a stable association between this environmental toxin and ET.", "title": "Blood Harmane (1-methyl-9h-pyrido[3,4-b]indole) Concentrations in Essential Tremor: Repeat Observation in Cases and Controls in New York" }, { "docid": "MED-4505", "text": "The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide (NO) synthase-independent NO production. Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides. This reductive pathway is enhanced during low oxygen tension and acidosis. A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate. We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise. Nine healthy, nonsmoking volunteers (age 30+/-2.3 years, VO(2max) 3.72+/-0.33 L/min) participated in this study, which had a randomized, double-blind crossover design. Subjects received dietary supplementation with sodium nitrate (0.1 mmol/kg/day) or placebo (NaCl) for 2 days before the test. This dose corresponds to the amount found in 100-300 g of a nitrate-rich vegetable such as spinach or beetroot. The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers. Dietary nitrate reduced VO(2max) from 3.72+/-0.33 to 3.62+/-0.31 L/min, P<0.05. Despite the reduction in VO(2max) the time to exhaustion trended to an increase after nitrate supplementation (524+/-31 vs 563+/-30 s, P=0.13). There was a correlation between the change in time to exhaustion and the change in VO(2max) (R(2)=0.47, P=0.04). A moderate dietary dose of nitrate significantly reduces VO(2max) during maximal exercise using a large active muscle mass. This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved: one that reduces VO(2max) and another that improves the energetic function of the working muscles. Copyright 2009 Elsevier Inc. All rights reserved.", "title": "Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise." }, { "docid": "MED-3895", "text": "Research suggests that pre-exercise sources of dietary carbohydrate with varying glycemic indexes may differentially affect metabolism and endurance. This study was designed to examine potential differences in metabolism and cycling performance after consumption of moderate glycemic raisins vs. a high glycemic commercial sports gel. Eight endurance-trained male (n = 4) and female (n = 4) cyclists 30 +/- 5 years of age completed 2 trials in random order. Subjects were fed 1 g carbohydrate per kilogram body weight from either raisins or sports gel 45 minutes prior to exercise on a cycle ergometer at 70% V(.-)O2max. After 45 minutes of submaximal exercise, subjects completed a 15-minute performance trial. Blood was collected prior to the exercise bout, as well as after the 45th minute of exercise, to determine serum concentrations of glucose, insulin, lactate, free fatty acids (FFAs), triglycerides, and beta-hydroxybutyrate. Performance was not different (p > 0.05) between the raisin (189.5 +/- 69.9 kJ) and gel (188.0 +/- 64.8 kJ) trials. Prior to exercise, serum concentrations of glucose and other fuel substrates did not differ between trials; however, insulin was higher (p < 0.05) for the gel (110.0 +/- 70.4 microU x ml(-1)) vs. raisin trial (61.4 +/- 37.4 microU x ml(-1)). After 45 minutes of exercise, insulin decreased to 14.2 +/- 6.2 microU x ml(-1) and 13.3 +/- 18.9 microU x ml(-1) for gel and raisin trials, respectively. The FFA concentration increased (+0.2 +/- 0.1 mmol x L(-1)) significantly (p < 0.05) during the raisin trial. Overall, minor differences in metabolism and no difference in performance were detected between the trials. Raisins appear to be a cost-effective source of carbohydrate for pre-exercise feeding in comparison to sports gel for short-term exercise bouts.", "title": "Metabolic and performance effects of raisins versus sports gel as pre-exercise feedings in cyclists." }, { "docid": "MED-4942", "text": "The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.", "title": "Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey." }, { "docid": "MED-973", "text": "There is no recognized definition of what constitutes a high fiber diet. Intakes of dietary fiber in different populations internationally vary widely from less than 20 g to more than 80 g per day. The types of foods contributing fiber also vary; in some countries cereals contribute the most fiber, in others leafy or root vegetables predominate. Vegetables have the highest fiber content per Kcal, and in most populations with fiber intakes over 50 g, vegetables contribute over 50% of total fiber intake. In rural Uganda, where the fiber hypothesis was first developed by Burkitt and Trowell, vegetables contribute over 90% of fiber intake. An experimental diet, the \"Simian\" diet, has been developed to mimic as closely as possible using human foods, the diet consumed by our simian ancestors the great apes. It is also similar to the Ugandan diet in containing large amounts of vegetables and 50 g fiber/1000 Kcal. Though nutritionally adequate, this diet is very bulky and not a suitable model for general recommendations. Dietary guidelines are that fat intake should be < 30% of energy, with a fiber intake of 20-35 g/d. These recommendations are inconsistent with a high fiber diet because, for people consuming more than about 2400 Kcal, low fiber choices for fruits and grains must be selected to keep dietary fiber intake within the range of 20-35 g. In a 30% fat, 1800 Kcal omnivorous diet, selection of wholemeal bread and whole fruit, results in a fiber intake over 35 g/d, and for and 1800 Kcal vegetarian diet, with substitution of modest amounts of peanut butter and beans for meats, dietary fiber intake goes up to 45 g/d. Thus, if it is desirable to promote the use of unrefined foods, the recommended dietary fiber intake should be a minimum of 15-20 g/1000 Kcal.", "title": "What is a high fiber diet?" }, { "docid": "MED-3524", "text": "Sleep, much like eating, is an essential part of life. The mechanisms of sleep are only partially clear and are the subject of intense research. There is increasing evidence showing that sleep has an influence on dietary choices. Both cross-sectional and epidemiologic studies have demonstrated that those who sleep less are more likely to consume energy-rich foods (such as fats or refined carbohydrates), to consume fewer portions of vegetables, and to have more irregular meal patterns. In this narrative review, we pose the opposite question: can ingested food affect sleep? The purpose of this review is to discuss the evidence linking diet and sleep and to determine whether what we eat and what kind of nutrients we obtain from the food consumed before bedtime matter. In addition, scientific evidence behind traditional sleep-promoting foods such as milk and some herbal products is briefly described. These are reviewed using data from clinical trials, mostly in healthy subjects. In addition, we discuss the possible mechanisms behind these observations. Lastly, we summarize our findings that emerging evidence confirms a link between diet and sleep. Overall, foods impacting the availability of tryptophan, as well as the synthesis of serotonin and melatonin, may be the most helpful in promoting sleep. Although there are clear physiological connections behind these effects, the clinical relevance needs to be studied further. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Diet promotes sleep duration and quality." }, { "docid": "MED-4087", "text": "Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.", "title": "Fibromyalgia and nutrition, what do we know?" }, { "docid": "MED-2970", "text": "There is increasing evidence that the postprandial state is an important contributing factor to chronic disease. The role of fruit phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest and the topic of the present paper. Two main questions are posed: first, what is the role of plant foods, specifically fruits rich in complex and simple phenolic compounds in postprandial metabolic management; and second, does the evidence support consuming these fruits with meals as a practical strategy to preserve health and lower risk for disease? This review provides an overview of the postprandial literature, specifically on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipaemia, glycaemia/insulinaemia and associated events, such as oxidative stress and inflammation. Among the identified well-controlled human trials using a postprandial paradigm, >50 % of the trials used wine or wine components and the remaining used various berries. Notwithstanding the need for more research, the collected data suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood, and when they are consumed with high fat and carbohydrate 'pro-oxidant and pro-inflammatory' meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrate in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.", "title": "Postprandial metabolic events and fruit-derived phenolics: a review of the science." }, { "docid": "MED-2304", "text": "Background There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. Methods and Findings We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1–14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass–, and social class–adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21–1.60), 1.95 (1.70–-2.25), 2.52 (2.13–3.00), and 4.04 (2.95–5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. Conclusions Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age. Editors' Summary Background. Every day, or so it seems, new research shows that some aspect of lifestyle—physical activity, diet, alcohol consumption, and so on—affects health and longevity. For the person in the street, all this information is confusing. What is a healthy diet, for example? Although there are some common themes such as the benefit of eating plenty of fruit and vegetables, the details often differ between studies. And exactly how much physical activity is needed to improve health? Is a gentle daily walk sufficient or simply a stepping stone to doing enough exercise to make a real difference? The situation with alcohol consumption is equally confusing. Small amounts of alcohol apparently improve health but large amounts are harmful. As a result, it can be hard for public-health officials to find effective ways to encourage the behavioral changes that the scientific evidence suggests might influence the health of populations. Why Was This Study Done? There is another factor that is hindering official attempts to provide healthy lifestyle advice to the public. Although there is overwhelming evidence that individual behavioral factors influence health, there is very little information about their combined impact. If the combination of several small differences in lifestyle could be shown to have a marked effect on the health of populations, it might be easier to persuade people to make behavioral changes to improve their health, particularly if those changes were simple and relatively easy to achieve. In this study, which forms part of the European Prospective Investigation into Cancer and Nutrition (EPIC), the researchers have examined the relationship between lifestyle and the risk of dying using a health behavior score based on four simply defined behaviors—smoking, physical activity, alcohol drinking, and fruit and vegetable intake. What Did the Researchers Do and Find? Between 1993 and 1997, about 20,000 men and women aged 45–79 living in Norfolk UK, none of whom had cancer or cardiovascular disease (heart or circulation problems), completed a health and lifestyle questionnaire, had a health examination, and had their blood vitamin C level measured as part of the EPIC-Norfolk study. A health behavior score of between 0 and 4 was calculated for each participant by giving one point for each of the following healthy behaviors: current non-smoking, not physically inactive (physical inactivity was defined as having a sedentary job and doing no recreational exercise), moderate alcohol intake (1–14 units a week; a unit of alcohol is half a pint of beer, a glass of wine, or a shot of spirit), and a blood vitamin C level consistent with a fruit and vegetable intake of at least five servings a day. Deaths among the participants were then recorded until 2006. After allowing for other factors that might have affected their likelihood of dying (for example, age), people with a health behavior score of 0 were four times as likely to have died (in particular, from cardiovascular disease) than those with a score of 4. People with a score of 2 were twice as likely to have died. What Do These Findings Mean? These findings indicate that the combination of four simply defined health behaviors predicts a 4-fold difference in the risk of dying over an average period of 11 years for middle-aged and older people. They also show that the risk of death (particularly from cardiovascular disease) decreases as the number of positive health behaviors increase. Finally, they can be used to calculate that a person with a health score of 0 has the same risk of dying as a person with a health score of 4 who is 14 years older. These findings need to be confirmed in other populations and extended to an analysis of how these combined health behaviors affect the quality of life as well as the risk of death. Nevertheless, they strongly suggest that modest and achievable lifestyle changes could have a marked effect on the health of populations. Armed with this information, public-health officials should now be in a better position to encourage behavior changes likely to improve the health of middle-aged and older people. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050012.", "title": "Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study" }, { "docid": "MED-2655", "text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.", "title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial" }, { "docid": "MED-1527", "text": "Importance Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. Objective To evaluate the association between vegetarian dietary patterns and mortality. Design Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Setting Adventist Health Study 2 (AHS-2), a large North American cohort. Participants A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions. Exposures Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan. Main Outcome and Measure The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. Results There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Conclusions and Relevance Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.", "title": "Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2" } ]
7040	Want to buy above market price?	[ { "docid": "331521", "text": "Buy and sell orders always include the price at which you buy/sell. That's how the market prices for stocks are determines. So if you want to place a buy order at 106, you can do that. When that order was fulfilled and you have the stock, you can place a sell order at 107. It will be processed as soon as someone places a buy order at 107. Theoretically you can even place sell orders for stocks you haven't even bought yet. That's called short selling. You do that when you expect a stock to go down in the future. But this is a very risky operation, because when you mispredict the market you might end up owing more money than you invested. No responsible banker will even discuss this with you when you can not prove you know what you are doing.", "title": "" }, { "docid": "184390", "text": "Yes, you can do this buy placing a conditional order to buy at market if the price moves to 106 or above. Once the price hits 106 your market order will hit the market and you will purchase the stock at 106 or above. You can also place a tack profit order at 107 linked to your initial conditional buy order, so that once you buy order is executed and you buy at 106, a take profit order will be executed only if the price reaches 107 or above. If the price never reaches 106, neither your market buy order or take profit order will hit the market and you won't buy or sell anything.", "title": "" } ]	[ { "docid": "126885", "text": "\"Yes it is possible, as long as the broker you use allows conditional orders. I use CMC Markets in Australia, and they allow free conditional orders either when initially placing a buy order or after already buying a stock. See the Place New Order box below: Once you have selected a stock to buy, the number of shares you want to buy and at what price you can place up to 3 conditional orders. The first condition is a \"\"Place order if...\"\" conditional order. Here you can place a condition that your buy order will only be placed onto the market if that condition is met first. Say the stock last traded at $9.80 and you only want to place your order the next day if the stock price moves above the current resistance at $10.00. So you would Place order if Price is at or above $10.00. So if the next day the price moves up to $10 or above your order will be placed onto the market. The second condition is a \"\"Stop loss\"\" conditional order. Here you place the price you want to sell at if the price drops to or past your stop loss price. It will only be placed on to the market if your buy order gets traded. So if you wanted to place your stop loss at $9.00, you would type in 9.00 in the box after \"\"If at or below ?\"\" and select if you want a limit or market order. The third condition is a \"\"Take profit\"\" conditional order. This allows you to take profits if the stock reaches a certain price. Say you wanted to take profits at 50%, that is if the price reached $15.00. So you would type in 15.00 in the box after \"\"If at or above ?\"\" and again select if you want a limit or market order. These conditional orders can all be placed at the time you enter your buy order and can be edited or deleted at any time. The broker you use may have a different process for entering conditional orders, and some brokers may have many more conditional orders than these three, so investigate what is out there and if you are confused in how to use the orders with your broker, simply ask them for a demonstration in how to use them.\"", "title": "" }, { "docid": "254542", "text": "If you want to buy once the price goes up to $101 or above you can place a conditional order to be triggered at $101 or above and for a limit order to entered to buy at $102. This will mean that as soon as the price reaches $101 or above, your limit order will enter the market and you will buy at any price from $102 or below. So if the price just trickles over $101 you will end up buying at around $101 or just over $101. However, if the price gaps above $101, say it gaps up to $101.50, then you will end up buying at around $101.50. If the price gaps up above $102, say $102.50, then your limit order at $102 will hit the market but it will not trade until the price drops back to $102 or below.", "title": "" }, { "docid": "59638", "text": "\"Yes there is, it is called a One-Cancels-the-Other Order (OCO). Investopedia defines a OCO order as: Definition of 'One-Cancels-the-Other Order - OCO' A pair of orders stipulating that if one order is executed, then the other order is automatically canceled. A one-cancels-the-other order (OCO) combines a stop order with a limit order on an automated trading platform. When either the stop or limit level is reached and the order executed, the other order will be automatically canceled. Seasoned traders use OCO orders to mitigate risk. I use CMC Markets in Australia, and they allow free conditional and OCO orders either when initially placing a buy order or after already buying a stock. See the Place New Order box below: Once you have selected a stock to buy, the number of shares you want to buy and at what price you can place up to 3 conditional orders. The first condition is a \"\"Place order if...\"\" conditional order. Here you can place a condition that your buy order will only be placed onto the market if that condition is met first. Say the stock last traded at $9.80 and you only want to place your order the next day if the stock price moves above the current resistance at $10.00. So you would Place order if Price is at or above $10.00. So if the next day the price moves up to $10 or above your order will be placed onto the market. The next two conditional orders form part of the OCO Orders. The second condition is a \"\"Stop loss\"\" conditional order. Here you place the price you want to sell at if the price drops to or past your stop loss price. It will only be placed on to the market if your buy order gets traded. So if you wanted to place your stop loss at $9.00, you would type in 9.00 in the box after \"\"If at or below ?\"\" and select if you want a limit or market order. The third condition is a \"\"Take profit\"\" conditional order. This allows you to take profits if the stock reaches a certain price. Say you wanted to take profits at 30%, that is if the price reached $13.00. So you would type in 13.00 in the box after \"\"If at or above ?\"\" and again select if you want a limit or market order. Once you have bought the stock if the stop order gets triggered then the take profit order gets cancelled automatically. If on the other hand the take profit order gets triggered then the stop loss order gets cancelled automatically. These OCO conditional orders can be placed either at the time you enter your buy order or after you have already bought the stock, and they can be edited or deleted at any time. The broker you use may have a different process for entering conditional and OCO orders such as these.\"", "title": "" }, { "docid": "278630", "text": "Firstly what are you trading that you could lose more than you put in? If you are simply trading stocks you will not lose more than you put in, unless you are trading on margin. A limit order is basically that, a limit on the maximum price you want your buy order bought at or the minimum price you want your sell order sold at. If you can't be glued to the screen all day when you place a limit order, and the market moves the opposite way, you may miss out on your order being executed. Even if you can be in front of the screen all day, you then have to decide if you want to chase the market of miss out on your purchase or sale. For example, if a stock is trading at $10.10 and you put a limit buy order to buy 1000 shares at or below $10.00 and the price keeps moving up to $10.20, then $10.30 and then $10.50, until it closes the day at $11.00. You then have the choice during the day to miss out on buying the shares or to increase your limit order in order to buy at a higher price. Sometime if the stock is not very liquid, i.e. it does not trade very often and has low volume, the price may hit $10.00 and you may only have part of your order executed, say 500 out of your 1000 shares were bought. This may mean that you may have to increase the price of your remaining order or be happy with only buying 500 shares instead of 1000. The same can happen when you are selling (but in reverse obviously). With market order, however, you are placing a buy order to buy at the next bid price in the depth or a sell order to sell at the next offer price in the depth. See the market depth table below: Note that this price depth table is taken before market open so it seems that the stock is somewhat illiquid with a large gap between the first and second prices in the buyers (bid) prices. When the market opened this gap is closed, as WBC is a major Australian bank and is quite liquid. (the table is for demonstration purposes only). If we pretend that the market was currently open and saw the current market depth for WBC as above, you could decide to place a limit sell order to sell 1000 shares at say $29.91. You would sell 100 shares straight away but your remaining 900 sell order will remain at the top of the Sellers list. If other Buyers come in at $29.91 you may get your whole sale completed, however, if no other Buyers place orders above $29.80 and other Sellers come into the market with sell orders below $29.91, your remaining order may never be executed. If instead you placed a market sell order you would immediately sell 100 shares at $29.91 and the remaining 900 shares at $29.80. (so you would be $99 or just over 0.3% worse off than if you were able to sell the full 1000 shares at $29.91). The question is how low would you have had to lower your limit order price if the price for WBC kept on falling and you had to sell that day? There are risks with whichever type of order you use. You need to determine what the purpose of your order is. Is it to get in or out of the market as soon as possible with the possibility of giving a little bit back to the market? Or is it to get the price you want no matter how long it takes you? That is you are willing to miss out on buying the shares (can miss out on a good buy if the price keeps rising for weeks or months or even years) or you are willing to miss out on selling them right now and can wait for the price to come back up to the price you were willing to sell at (where you may miss out on selling the shares at a good price and they keep on falling and you give back all your profits and more). Just before the onset of the GFC I sold some shares (which I had bought a few years earlier at $3.40) through a market order for $5.96. It had traded just above $6 a few days earlier, but if instead of a market order I had placed a limit order to sell at $6.00 or more I would have missed out on the sale. The price never went back up to $6 or above, and the following week it started dropping very quickly. It is now trading at about $1.30 and has never gone back above $2.00 (5.5 years later). So to me placing a limit order in this case was very risky.", "title": "" }, { "docid": "389329", "text": "Consider the mechanic which actually drives the 'price' of a stock. In simplest terms, the 'price' of a stock is the price at which the most recent trade occurred. ie: if the price of IBM is $100/share, that means the last time someone bought IBM stock, they paid $100. Above and below the 'spot price', are dozens/hundreds/thousands of buyers and sellers who have placed orders that no one is yet willing to match. ie: if IBM's spot price is at $100, there could still be 10,000 people willing to sell for $101 (called the 'ask' price, for the lowest price someone is currently willing to sell at), and 15,000 willing to buy for $99 (called the 'bid' price, for the highest price someone is currently willing to buy for). Until someone is willing to buy for $101, then no one will be able to sell at $101. Until someone is willing to sell for $99, no one will be able to buy for $99. Typically orders are placed in the market at a particular limit. Meaning that those orders to buy at $99/sell at $101 are already in the 'system', and will be matched immediately as soon as someone is willing to meet the price on the other side. Now consider general market economics: high demand drives up price, and high supply drives down price. If the details above for IBM were yesterday, and today some news came out that IBM was laying off employees, imagine that another 10,000 people who held shares wanted to sell. Now there would be 20,000 sellers and only 15,000 buyers. If those new sellers were aggressive about wanting to sell, they would have to drop their price to $99, to match the highest buyers in the market. Put together, this means that as more sellers enter the market, supply of shares increases, driving down price. Conversely, as more buyers enter the market, demand for shares increases, driving up share price. As a result of the above, you can say that (all else being equal) if price for a stock goes up, there were more buyers that day, and if price goes down, there were more sellers that day. On the face of it, that is not necessarily true, because you could have the same number of buyers and sellers, one side could have simply decreased/increased their acceptable price to match the other side.", "title": "" }, { "docid": "494295", "text": "There are a couple of things you could do, but it may depend partly on the type of orders your broker has available to you. Firstly, if you are putting your limit order the night before after close of market at the top of the bids, you may be risking missing out if bid & offer prices increase by the time the market opens the next day. On the other hand, if bid & offer prices fall at the open of the next day you should get your order filled at or below your limit price. Secondly, you could be available at the market open to see if prices are going up or down and then work out the price you want to buy at then and work out the quantity you can buy at that price. I personally don't like this method because you usually get too emotional, start chasing the market if prices start rising, or start regretting buying at a price and prices fall straight afterwards. My preferred method is this third option. If your broker provides stop orders you can use these to both get into and out of the market. How they work when trying to get into the market is that once you have done your analysis and picked a price that you would want to purchase at, you put a stop buy order in. For example, the price closed at $9.90 the previous day and there has been resistance at $10.00, so you would put a stop buy trigger if the price goes over $10, say $10.01. If your stop buy order gets triggered you can have either a buy market order or a limit order above $10.01 (say $10.02). The market order would go through immediately whilst the limit order would only go through if the price continues going to $10.02 or above. The advantage of this is that you don't get emotional trying to buy your securities whilst sitting in front of the screen, you do your analysis and set your prices whilst the market is closed, you only buy when the security is rising (not falling). As your aim is to be in long term you shouldn't be concerned about buying a little bit higher than the previous days close. On the other hand if you try and buy when the price is falling you don't know when it will stop falling. It is better to buy when the price shows signs of rising rather than falling (always follow the trend).", "title": "" }, { "docid": "259178", "text": "You bought the right – but not the obligation – to buy a certain number of shares at $15 from whomsoever sold you the option, and you paid a premium for it. You can choose whether you want to buy the shares at $15 during the period agreed upon. If you call for the shares, the other guy has to sell the shares to you for $15 each, even if the market price is higher. You can then turn around and promptly resell the purchased shares at the higher market price. If the market price never rises above $15 at any time while the option is open, you still have the right to buy the shares for $15 if you choose to do so. Most rational people would let the option expire without exercising it, but this is not a legal requirement. Doing things like buying shares at $15 when the market price is below $15 is perfectly legal; just not very savvy. You cannot cancel the option in the sense of going to the seller of the option and demanding your premium money back because you don't intend to exercise the option because the market price is below $15. Of course, if the market price is above $15 and you tell the seller to cancel the contract, they will be happy to do so, since it lets them off the hook. They may or may not give you the premium back in this case.", "title": "" }, { "docid": "362212", "text": "Buying stocks is like an auction. Put in the price you want to pay and see if someone is willing to sell at that price. Thing to remember about after hours trading; There is a lot less supply so there's always a larger bid/ask price spread. That's the price brokers charge to handle the stocks they broker over and above the fee. That means you will always pay more after the market closes. Unless it is bad news, but I don't think you want to buy when that happens. I think a lot of the after market trading is to manipulate the market. Traders drive up the price overnight with small purchases then sell their large holdings when the market opens.", "title": "" }, { "docid": "212685", "text": "At any point of time, buyer wants to purchase a stock at lesser price and seller wants to sell the stock at a higher price. Let's consider this scenario Company XYZ is trading at 100$, as stated above buyer wants to purchase at lower price and seller at higher price, this information will be available in Market depth, let's consider there are 5 buyers and 5 sellers, below are the details of their orders Buyers List Sellers List Highest order in buyers list will contain the bid price and bid quantity, Lowest order in Sellers list will contain the offer price and offer quantity. Now, if I want to buy 50 Stocks of company XYZ, need to place an order first, it can be either limit or Market. Limit Order : In this order, I will mention the price(buy price) at which I wish to buy, if there is any seller selling the stock less than or equal to price I have mentioned, then the order will be executed else it will be added to buyers list Market Order : In this order, I will not mention the price, if I wish to purchase 50 Stocks, then it will find the lowest offer price and buy stocks, in our case it will be 101. if I wish to purchase 200 Stocks, then it will find the lowest offer price and buy stocks, in our case it will be 2 transactions, since entire request cannot be accommodated in single order Usually the volume(Ask Volume and Offer Volume) being displayed are all Limit orders and not Market orders, Market orders are executed immediately. This is just an example, However several transactions are executed within a second, hence we will get to know the exact value only after the order is completed(executed)", "title": "" }, { "docid": "178446", "text": "\"Correcting Keith's answer (you should have read about these details in the terms and conditions of your bank/broker): Entrustment orders are like a \"\"soft\"\" limit order and meaningless without a validity (which is typically between 1 and 5 days). If you buy silver at an entrustment price above market price, say x when the market offer is m, then parts of your order will likely be filled at the market price. For the remaining quantity there is now a limit, the bank/broker might fill your order over the next 5 days (or however long the validity is) at various prices, such that the overall average price does not exceed x. This is different to a limit order, as it allows the bank/broker to (partially) buy silver at higher prices than x as long as the overall averages is x or less. In a limit set-up you might be (partially) filled at market prices first, but if the market moves above x the bank/broker will not fill any remaining quantities of your order, so you might end up (after a day or 5 days) with a partially filled order. Also note that an entrustment price below the market price and with a short enough validity behaves like a limit price. The 4th order type is sort of an opposite-side limit price: A stop-buy means buy when the market offer quote goes above a certain price, a stop-sell means sell when the market bid quote goes below a certain price. Paired with the entrusment principle, this might mean that you buy/sell on average above/below the price you give. I don't know how big your orders are or will be but always keep in mind that not all of your order might be filled immediately, a so-called partial fill. This is particularly noteworthy when you're in a pro-rata market.\"", "title": "" }, { "docid": "169062", "text": "\"It's good to ask this question, because this is one of the fundamental dichotomies in market microstructure. At any time T for each product on a (typical) exchange there are two well-defined prices: At time T there is literally no person in the market who wants to sell below the ask, so all the people who are waiting to buy at the bid (or below) could very well be waiting there forever. There's simply no guarantee that any seller will ever want to part with their product for a lesser price than they think it's worth. So if you want to buy the product at time T you have a tough choice to make: you get in line at the bid price, where there's no guarantee that your request will ever be filled, and you might never get your hands on the product you decide that owning the product right now is more valuable to you than (ask - bid) * quantity, so you tell the exchange that you're willing to buy at the ask price, and the exchange matches you with whichever seller is first in line Now, if you're in the market for the long term, the above choice is completely immaterial to you. Who cares if you pay $10.00 * 1000 shares or $10.01 * 1000 shares when you plan to sell 30 years from now at $200 (or $200.01)? But if you're a day trader or anyone else with a very short time horizon, then this choice is extremely important: if the price is about to go up several cents and you got in line at the bid (and never got filled) then you missed out on some profit if you \"\"cross the spread\"\" to buy at the ask and then the price doesn't go up (or worse, goes down), you're screwed. In order to get out of the position you'll have to cross the spread again and sell at at most the bid, meaning you've now paid the spread twice (plus transaction fees and regulatory fees) for nothing. (All of the above also applies in reverse for selling at the ask versus selling at the bid, but most people like to learn in terms of buying rather than selling.)\"", "title": "" }, { "docid": "377186", "text": "If you want to invest in the stock market, whether over a shorter period of 1 to 2 years or over a longer period of 10 or 20 years or longer you need to take some precautions and have a written investment plan with a risk management strategy incorporated in your plan. Others have said that 1 to 2 years is too short to invest in the stock market as the stock market can have a correction and fall by 50%. But it doesn't matter if you invest for 1 year or if you invest for 50 years, the stock market can still fall by 50% just before you plan to withdraw your funds. What you need to figure out is a way to get out before the market falls by 40% to 50%. A simple way to do this is to use technical indicators to warn you when a market trend is starting to change and that it is time to get out of the market. Two simple indicators you can use on a market index are the Rate of Change (ROC) indicator and the 100 week Moving Average (MA). Below is a 10 year weekly chart of the S&P500 with these two indicators charted. They show good times to get into the market and good times to get out. If you are using the 100 week MA you would buy in when the price crosses above the MA line and sell when the price crosses below the MA line. If you are using the ROC indicator you would buy in when the ROC indicator crosses above the zero line and sell when the ROC indicator crosses below the zero line. So your investment plan could be to buy an Index ETF representing the S&P500 when the ROC moves above zero and sell when it crosses below zero. You can also place a trailing stop loss of 10% to protect you in case of a sudden fall over a couple of days. You can manage your investments in as little as 10 minutes per week by checking the chart once per week and adjusting your stop loss order. If you want to progressively add to your investment each month you could check the charts and only add any new funds if both the ROC is above zero and sloping upwards. Another option for adding new funds could be if the price is above the MA and moving further away from the MA. All these rules should be incorporated into your investment plan so that you are not basing your decisions based on emotions. There are many other Technical Analysis Indicators you could also learn about to make better educated decisions about your stock market investments. However, what I have provided here is enough for anyone to test over different indexes and time frames and do their own paper trading on to gain some confidence before placing any real money on the table.", "title": "" }, { "docid": "447886", "text": "\"After learning about things that happened in the \"\"flash crash\"\" I always use limit orders. In an extremely rare instance if you place a market order when there is a some glitch, for example some large trader adds a zero at the end of their volume, you could get an awful price. If I want to buy at the market price, I just set the limit about 1% above the market price. If I want to sell, I set the limit 1% below the market price. I should point out that your trade is not executed at the limit price. If your limit price on a buy order is higher than the lowest offer, you still get filled at the lowest offer. If before your order is submitted someone fills all offers up to your limit price, you will get your limit price. If someone, perhaps by accident, fills all orders up to twice your limit price, you won't end up making the purchase. I have executed many purchases this way and never been filled at my limit price.\"", "title": "" }, { "docid": "28604", "text": "\"The current stock price you're referring to is actually the price of the last trade. It is a historical price – but during market hours, that's usually mere seconds ago for very liquid stocks. Whereas, the bid and ask are the best potential prices that buyers and sellers are willing to transact at: the bid for the buying side, and the ask for the selling side. But, think of the bid and ask prices you see as \"\"tip of the iceberg\"\" prices. That is: The \"\"Bid: 13.20 x200\"\" is an indication that there are potential buyers bidding $13.20 for up to 200 shares. Their bids are the highest currently bid; and there are others in line behind with lower bid prices. So the \"\"bid\"\" you're seeing is actually the best bid price at that moment. If you entered a \"\"market\"\" order to sell more than 200 shares, part of your order would likely be filled at a lower price. The \"\"Ask: 13.27 x1,000\"\" is an indication that there are potential sellers asking $13.27 for up to 1000 shares. Their ask prices are the lowest currently asked; and there are others in line behind with higher ask prices. So the \"\"ask\"\" you're seeing is the best asking price at that moment. If you entered a \"\"market\"\" order to buy more than 1000 shares, part of your order would likely be filled at a higher price. A transaction takes place when either a potential buyer is willing to pay the asking price, or a potential seller is willing to accept the bid price, or else they meet in the middle if both buyers and sellers change their orders. Note: There are primarily two kinds of stock exchanges. The one I just described is a typical order-driven matched bargain market, and perhaps the kind you're referring to. The other kind is a quote-driven over-the-counter market where there is a market-maker, as JohnFx already mentioned. In those cases, the spread between the bid & ask goes to the market maker as compensation for making a market in a stock. For a liquid stock that is easy for the market maker to turn around and buy/sell to somebody else, the spread is small (narrow). For illiquid stocks that are harder to deal in, the spread is larger (wide) to compensate the market-maker having to potentially carry the stock in inventory for some period of time, during which there's a risk to him if it moves in the wrong direction. Finally ... if you wanted to buy 1000 shares, you could enter a market order, in which case as described above you'll pay $13.27. If you wanted to buy your shares at no more than $13.22 instead, i.e. the so-called \"\"current\"\" price, then you would enter a limit order for 1000 shares at $13.22. And more to the point, your order would become the new highest-bid price (until somebody else accepts your bid for their shares.) Of course, there's no guarantee that with a limit order that you will get filled; your order could expire at the end of the day if nobody accepts your bid.\"", "title": "" }, { "docid": "550643", "text": "If you can afford the cost and risk of 100 shares of stock, then just sell a put option. If you can only afford a few shares, you can still use the information the options market is trying to give you -- see below. A standing limit order to buy a stock is essentially a synthetic short put option position. [1] So deciding on a stock limit order price is the same as valuing an option on that stock. Options (and standing limit orders) are hard to value, and the generally accepted math for doing so -- the Black-Scholes-Merton framework -- is also generally accepted to be wrong, because of black swans. So rather than calculate a stock buy limit price yourself, it's simpler to just sell a put at the put's own midpoint price, accepting the market's best estimate. Options market makers' whole job (and the purpose of the open market) is price discovery, so it's easier to let them fight it out over what price options should really be trading at. The result of that fight is valuable information -- use it. Sell a 1-month ATM put option every month until you get exercised, after which time you'll own 100 shares of stock, purchased at: This will typically give you a much better cost basis (several dollars better) versus buying the stock at spot, and it offloads the valuation math onto the options market. Meanwhile you get to keep the cash from the options premiums as well. Disclaimer: Markets do make mistakes. You will lose money when the stock drops more than the option market's own estimate. If you can't afford 100 shares, or for some reason still want to be in the business of creating synthetic options from pure stock limit orders, then you could maybe play around with setting your stock purchase bid price to (approximately): See your statistics book for how to set ndev -- 1 standard deviation gives you a 30% chance of a fill, 2 gives you a 5% chance, etc. Disclaimer: The above math probably has mistakes; do your own work. It's somewhat invalid anyway, because stock prices don't follow a normal curve, so standard deviations don't really mean a whole lot. This is where market makers earn their keep (or not). If you still want to create synthetic options using stock limit orders, you might be able to get the options market to do more of the math for you. Try setting your stock limit order bid equal to something like this: Where put_strike is the strike price of a put option for the equity you're trading. Which option expiration and strike you use for put_strike depends on your desired time horizon and desired fill probability. To get probability, you can look at the delta for a given option. The relationship between option delta and equity limit order probability of fill is approximately: Disclaimer: There may be math errors here. Again, do your own work. Also, while this method assumes option markets provide good estimates, see above disclaimer about the markets making mistakes.", "title": "" }, { "docid": "561997", "text": "I think your premise is slightly flawed. Every investment can add or reduce risk, depending on how it's used. If your ordering above is intended to represent the probability you will lose your principal, then it's roughly right, with caveats. If you buy a long-term government bond and interest rates increase while you're holding it, its value will decrease on the secondary markets. If you need/want to sell it before maturity, you may not recover your principal, and if you hold it, you will probably be subject to erosion of value due to inflation (inflation and interest rates are correlated). Over the short-term, the stock market can be very volatile, and you can suffer large paper losses. But over the long-term (decades), the stock market has beaten inflation. But this is true in aggregate, so, if you want to decrease equity risk, you need to invest in a very diversified portfolio (index mutual funds) and hold the portfolio for a long time. With a strategy like this, the stock market is not that risky over time. Derivatives, if used for their original purpose, can actually reduce volatility (and therefore risk) by reducing both the upside and downside of your other investments. For example, if you sell covered calls on your equity investments, you get an income stream as long as the underlying equities have a value that stays below the strike price. The cost to you is that you are forced to sell the equity at the strike price if its value increases above that. The person on the other side of that transaction loses the price of the call if the equity price doesn't go up, but gets a benefit if it does. In the commodity markets, Southwest Airlines used derivatives (options to buy at a fixed price in the future) on fuel to hedge against increases in fuel prices for years. This way, they added predictability to their cost structure and were able to beat the competition when fuel prices rose. Even had fuel prices dropped to zero, their exposure was limited to the pre-negotiated price of the fuel, which they'd already planned for. On the other hand, if you start doing things like selling uncovered calls, you expose yourself to potentially infinite losses, since there are no caps on how high the price of a stock can go. So it's not possible to say that derivatives as a class of investment are risky per se, because they can be used to reduce risk. I would take hedge funds, as a class, out of your list. You can't generally invest in those unless you have quite a lot of money, and they use strategies that vary widely, many of which are quite risky.", "title": "" }, { "docid": "498075", "text": "\"The response to this question will be different depending which of the investment philosophies you are using. Value investors look at the situation the company is in and try to determine what the company is worth and what it will be worth in the future. Then they look at the current stock price and decide whether or not the stock is priced at a good deal or not. If the stock price is priced lower than they believe the company is worth, they would want to buy stock, and if the price rises above what they believe to be the true value, they would sell. These types of investors are not looking at the history or trend of what the price has done in the past, only what the current price is and where they believe the price should be in the future. Technical analysis investors do something different. It is their belief that as stock prices go up and down, they generally follow patterns. By looking at a chart of what a stock price has been in the past, they try to predict where it is headed, and buy or sell based on that prediction. In general, value investors are longer-term investors, and technical analysis investors are short-term investors. The advice you are considering makes a lot of sense if you are using technical analysis. If you have a stock that is trending down, your strategy probably tells you to sell; buying more in the hopes of turning things around would be seen as a mistake. It is like the gambler in Vegas who keeps playing a game he is losing, hoping that his luck changes. However, for the value investor, the historical price of a stock, and even the amount you currently have gained or lost in the stock, are essentially ignored. All that matters is whether or not the stock price is above or below the true value determined by the investor. For him, if the stock price falls and he believes the company still has a high value, it could be a signal to buy more. The above advice doesn't really apply for them. Many investors don't follow either of these strategies. They believe that it is too difficult and risky to try to predict the future price of an individual stock. Instead, they invest in many companies all at once using index mutual funds, believing that the stock market as a whole always heads up over a long time frame. Those investors don't care at all if the prices of stock are going up or down. They simply keep investing each month, and hold until they have another use for the money. The above advice isn't useful for them at all. No matter which kind of investing you are doing, the most important thing is to pick a strategy you believe in and follow the plan without emotion. Emotions can cause investors to make mistakes and start buying when their strategy tells them to sell. Instead of trying to follow fortune cookie advice like \"\"Don't throw good money after bad,\"\" choose an investment strategy, make a plan, test it, and follow it, cautiously (after all, it may be a bad plan). For what it is worth, I am the third type of investor listed above. I don't buy individual stocks, and I don't look at the stock prices when investing more each month. Your description of your own strategy as \"\"buy and hold\"\" suggests you might prefer the same approach.\"", "title": "" }, { "docid": "514841", "text": "A limit order is simply an order to buy at a maximum price or sell at a minimum price. For example, if the price is $100 and you want to sell if the price rises to $110, then you can simply put a limit order to sell at $110. The order will be placed in the market and when the price reaches $110 your order will be executed. If the price gaps at the open to $111, then you would end up selling for $111. In other words you will get a minimum of $110 per share. A stop limit order is where you put a stop loss order, which when it gets triggered, will place a limit order in the market for you. For example, you want to limit your losses by placing a stop loss order if the price drops to $90. If you chose a market order with your stop loss as soon as the price hits $90 your stop loss would be triggered and the shares would sell at the next available price, usually at $90, but could be less if the market gaps down past $90. If on the other hand you placed a limit order at $89.50 with your stop loss, when the stop loss order gets triggered at $90 your limit order will be placed into the market to sell at $89.50. So you would get a minimum of $89.50 per share, however, if the market gaps down below $89.50 your order will be placed onto the market but it won't sell, unless the price goes back to or above $89.50. Hope this helps.", "title": "" }, { "docid": "581579", "text": "\"For any large company, there's a lot of activity, and if you sell at \"\"market\"\" your buy or sell will execute in seconds within a penny or two of the real-time \"\"market\"\" price. I often sell at \"\"limit\"\" a few cents above market, and those sell within 20 minutes usually. For much smaller companies, obviously you are beholden to a buyer also wanting that stock, but those are not on major exchanges. You never see whose buy order you're selling into, that all happens behind the curtain so to speak.\"", "title": "" }, { "docid": "475019", "text": "\"The short version of JB King's excellent answer is that the company will typically buy back shares from the open market at market price. Sometimes, it will specifically target larger stakeholders, even controlling interests, who are making noise that they want to divest; if such an investor were to just dump their stock on the open market, neither the investor nor the company would be very happy with the resulting price collapse. In those cases, the company may offer an incentive price above market rates. In recent times, the investor looking to divest has often been the U.S. Government, who received stock in return for bailouts, and (with notable exceptions) turned a modest profit on many of them. Not enough to break even on the entire bailout, but the Government didn't just throw $700 billion in taxpayer money down a hole as conservative pundits would have you believe. In the '80s, a specific type of buy-back was made famous, called the \"\"leveraged buyout\"\". Basically, the company took out a huge loan against itself, and used that money to buy up all the company's publicly-traded shares, essentially becoming a private company. This became a popular tool among private equity groups, for better and worse.\"", "title": "" }, { "docid": "251002", "text": "When using the Stochastic Indicator your basic aim is to buy (go long) when the stochastic becomes oversold (goes below 20%) and then the %K line crosses above the %D line at a market low, and to sell (go short) when the stochastic becomes overbought (goes above 80%) and then the %K line crosses below the %D line at a market high. Other indicators or candlestick patters can also be used to further confirm the trade. Below is a chart of a trade I recently took on GUD.AX using the Slow Stochastic in combination with support and resistance levels as well as a candlestick pattern. When I conducted my stock search on the evening of 28th July 2015, GUD was one of the results from the search that I particularly liked. The Slow Stochastic had just made a crossover in the oversold area just as the price was bouncing off its recent lows at the support line. But what I really like about this opportunity was that there was also a bullish reversal candle (a Hammer) at this short term market bottom. The high for the day was $8.34, so I placed a stop buy order to buy the stock tomorrow if the price opened or moved above this high of today. So I would only buy if the stock hit or moved above $8.35 during the next days trading. So if the stock opened and stayed below the previous day's high I would not buy the stock and my order would be canceled at the end of the day. This is very important because it stops you from getting into trades that don't go in the direction you want. If this happens then you could check the chart again after market close to see if it is still worthwhile to place a new order for the next day. On the 29th July 2015 the stock did open higher at $8.42 (which is where my order got executed) and closed at $8.46. So I ended up buying slightly above my target price but it did move higher on the day, so a successful entry overall. I had placed my initial stop loss at $8.09 (just below the low of the previous day of $8.10). If the trade had gone against me in the following days the most I would have lost was 1% of my total account capital. My target for this trade was $9.86 (just below the resistance line near $10), which would represent a 5% gain against my total account capital (or approx. 16.7% gain on the trade). So my win to loss ratio was 5:1. As you can see from the chart, the next day gapped up at the open and prices continued moving up strongly during the day. The next day was a slightly negative day, and then a few days later, on the 5th August 2015 my target price of $9.86 was reached (with a high of $9.88 for that day), so my order was closed for a total profit of 16.7% on the face value of the trade. However, as I bought on margin (using CFDs) my actual profit on the initial margin I had invested was 167%. My total time in the trade was 7 days, and I spent about an hour in the evening doing my searches and placing my orders, then less than 10 minutes managing the trade each evening after market close. The stock did go up a bit further after my profit target was reached, but the day after that the price started to fall as the price hit the resistance line and the Slow Stochastic did a crossover in the overbought area. Overall, this was a very ideal trade and I was very happy with it. Not all my trades reach my profit targets and I may get stopped out at a smaller profit or I might make a small loss (as I move my stops up as the price moves up). The key to successful trading over the long term is to keep you losses small and let your profits run (with my longer term trend trading I don't have profit targets and let my profits run until I get stopped out, but with my shorter term trading I do use a profit target usually 5 or 6 times the size of my initial stop). If you have an average win to average loss ratio of 3:1 or higher and have a success rate of 50% winners you will make money over the long term.", "title": "" }, { "docid": "536788", "text": "The safest real estate investment is to underpay. In most areas the market is very public. Flippers are abundant, because most people want a move-in ready home, and as it is leveraged, they will overpay for that luxury. Buy an under market, and you are safer. The people who lose their shirts buy new condos at market rates at the peak of the market. At the same time, people are purchasing starter homes that need a little work, and stay well above water. Always remember you can't change the location of a home, but you can change almost everything else. Find a well located but beat up home priced well under market, and financially you will generally do very well.", "title": "" }, { "docid": "538979", "text": "On June 30 2015, the value of a key should be exactly the expected revenue from selling the chest contents, owing to the fact that the next day the keys become worthless. Looking at the steam community market, it seems like the value of a key is higher than this, but lower than 2.50? If that's true, then since the price of a key is higher than the expected revenue from selling the chest contents as you say, then you can see that at some point the value of a key will have to go down. And as you get closer to the cutoff date, the price will fall faster. It's not quite the same, but this pattern is usually what you see in the ticket resale market on say, StubHub. If there's something about keys that keeps their worth above the expected value of selling chest contents (some value to the flexibility that keys offer over other tradable items maybe?), then in the short run that won't change due to this distant deadline, just because it's so far off. People will still want the flexibility keys offer. Orthodox economics might suggest sell sooner rather than later, but certainly don't wait too long. Different people react differently though. If there are a lot of panicky people who sell their keys after hearing this news, it might be a good time to buy. Of course it's a gamble, but if you trust in whatever force keeps keys priced above the expected value of the loot they can buy, then that force should win out in the medium term and you could turn a profit.", "title": "" }, { "docid": "168080", "text": "\"The reason for this is arbitrage. In an free and open market, investments that are certain to generate above-average profits would do so by being sold cheaply, while having a high return on investment after that. But in a free market, prices are set by supply and demand. There is a high demand and little supply for investments that would certainly outperform the market. The demand is in fact so high, that the purchase price rises to the point of eliminating that excess return. And with high-frequency automated trading, that price hike is instant. But who would even want to sell such guaranteed outperformers in the first place? Of course, there are uncertainties associated with stocks, and individual stocks therefore move independently. As \"\"the market\"\" is an average, some stocks will therefore beat the market over certain time periods. That's random statistical variation. The only realistic path to above-average returns is to accept higher risks. As discussed above, nobody wants to sell you safe bets. But risky bets are another matter. Different actors will price risk differently. If you aren't worried much about risk, you can pick up stocks that are cheap by your standards. That is possible only because such stocks aren't cheap by risk-averse standards. Looking a bit deeper, we see that arbitrage works in a free market because there's essentially perfect information. But risk is precisely the absence of such information, and that can lead to price variations. Yet, as the lack of information means a lack of certainty, you can't use this to reliably beat the market.\"", "title": "" }, { "docid": "494727", "text": "\"Re: A trader when buying needs to buy at the ask price and when selling needs to sell at the bid price. So how can a trade happen 'in between' the bid and ask? Saying the trade can happen \"\"in between\"\" the bid & ask is simplistic. There is a time dimension to the market. It's more accurate to say that an order can be placed \"\"in between\"\" the current best bid & ask (observed at time T=0), thus establishing a new level for one or the other of those quoted prices (observed at time T>0). If you enter a market order to buy (or sell), then yes, you'll generally be accepting the current best ask (or best bid) with your order, because that's what a market order says to do: Accept the current best market price being offered for your kind of transaction. Of course, prices may move much faster than your observation of the price and the time it takes to process your order – you're far from being the only participant. Market orders aside, you are free to name your own price above or below the current best bid & ask, respectively. ... then one could say that you are placing an order \"\"in between\"\" the bid and ask at the time your order is placed. However – and this is key – you are also moving one or the other of those quoted prices in the process of placing your above-bid buy order or your below-ask sell order. Then, only if somebody else in the market chooses to accept your new ask (or bid) does your intended transaction take place. And that transaction takes place at the new ask (or bid) price, not the old one that was current when you entered your order. Read more about bid & ask prices at this other question: (p.s. FWIW, I don't necessarily agree with the assertion from the article you quoted, i.e.: \"\"By looking for trades that take place in between the bid and ask, you can tell when a strong trend is about to come to an end.\"\" I would say: Maybe, perhaps, but maybe not.)\"", "title": "" }, { "docid": "31933", "text": "The Limit Order are matched based on amount and time. The orders are listed Highest to Lowest on the Buy Side. The orders are listed Lowest to Highest on the Sell Side. If there are 2 Sell orders for same amount the order which is first in time [fractions of milliseconds] is first. The about is the example as to how the orders would look like on any exchange. Now the highest price the buyer is ready to pay is 20.21 and the lowest price a seller is ready to sell for is 20.25. Hence there is no trade. Now if a new Buy order comes in at 20.25, it matches with the sell and the deal is made. If a new Buy order comes in at 20.30, it still matches at 20.25. Similarly if a Sell order come in at 20.21, it matches and a deal is made. If a Sell order come in at 20.11, it still matches 20.21. Incase of market order, with the above example if there is a Buy order, it would match with the lowest sell order at 20.25, if there is not enough quantity , it would match the remaining quantity to the next highest at 20.31 and continue down. Similarly if there is a Sell market order, the it would match to the maximum a seller is ready to buy, ie 20.21, if there is not sufficient buy quantity at 20.21, it will match with next for 20.19 If say there are new buy order at 20.22 and sell orders at 20.24, these will sit first the the above queue to be matched. In your above example the Lowest Sell order was at 20.10 at time t1 and hence any buy order after time t1 for amount 20.10 or greater would match to this and the price would be 20.10. However if the Buy order was first ie at t1 there was a buy order for 20.21 and then at time later than t1, there is a sell order for say 20.10 [amount less than or equal to 20.21] it would match for 20.21. Essentially the market looks at who was the first to sell at lower price or who was the first to buy at higher price and then decide the trade. Edit [To Clarify xyz]: Say if there is an Sell order at $10 Qty 100. There is a buyer who is willing to pay Max $20 and is looking for Qty 500. Your key assumption that the Buyer does not know the current SELL price of $10 is incorrect. Now there are multiple things, the Buyer knows the lowest Sell order is at $10, he can put a matching Buy order at $10 Qty 100, and say $11 Qty 100 etc. This is painful. Second, lets say he puts a Buy order at $10 Qty 100, by the time the order hits the system someone else has put the trade at $10 and his order is fulfilled. So this buyer has to keep looking at booking and keep making adjustments, if its a large order, it would be extremely difficult and frustrating for this Buyer. Hence the logic of giving preference. The later Buy order says ... The Max I can pay is $20, match eveything at the current price and get the required shares.", "title": "" }, { "docid": "371205", "text": "\"Alrighty. So your question is, how confident are people that FB stock will close above a certain price at a certain time. A \"\"call\"\" option contract allows you to buy shares in the future at a certain price. FB calls are available for March of 2013. The number in the \"\"strike\"\" column is the price you can buy FB stock at on the given date. Let's take the \"\"33.00\"\" strike. This allows you to buy FB shares at $33 each next March. If at that time it turns out they're worth $50 each, you can buy them at $33, then immediately sell them on the open market for $50, making money. The person selling you the option knows that there's a chance the price will be above $33 in March, so he's going to charge you a few bucks to cover that possibility. In this case, he's charging you $5.30 (as of me writing this). So, you can have the option to buy FB shares at $33 each for $5.30. This means the guy selling you the option is reasonably confident that in March, FB stock will be at or under $38.50, otherwise he'd lose money when you exercised the option. Therefore, $38.50 is the option market's best guess as to the highest FB stock will be going for in March.\"", "title": "" }, { "docid": "376399", "text": "He can buy at 69.95 or 69.70 or whatever because he already has all the shares. The HFT bought at a cheaper price earlier. The HFT has all the shares. Now he's testing the guy who won't go above 70.00 with small orders. When he sees that this guy is willing to buy 10 at 70.00 the HFT makes a limit order of all the shares in the market at 70.00 when he got them all already at 69.95. Whatever doesn't get bought up goes back into the market at the price the HFT originally bought at. The HFT was in line ahead of the guy who won't go above 70.00 as soon as he saw him buying. Like at the horse race, remember?", "title": "" }, { "docid": "53041", "text": "\"A \"\"market maker\"\" is someone that is contractually bound, by the exchange, to provide both bid and ask prices for a given volume (e.g. 5000 shares). A single market maker usually covers many stocks, and a single stock is usually covered by many market makers. The NYSE has \"\"specialists\"\" that are market makers that also performed a few other roles in the management of trading for a stock, and usually a single issue on the NYSE is covered by only one market maker. Market makers are often middlemen between brokers (ignoring stuff like dark pools, and the fact that brokers will often trade stocks internally among their own clients before going to the exchange). Historically, the market makers gave up buy/sell discretion in exchange for being the \"\"go-to guys\"\" for anyone wanting to trade in that stock. When you told your broker to buy a stock for you, he didn't hook you up with another retail investor; he went to the market maker. Market makers would also sometimes find investors willing to step in when more liquidity was needed for a security. They were like other floor traders; they hung out on the exchange floors and interacted with traders to buy and sell stocks. Traders came to them when they wanted to buy one of the specialist's issues. There was no public order book; just ticker tape and a quote. It was up to the market maker to maintain that order book. Since they are effectively forbidden from being one-sided traders in a security, their profit comes from the bid-ask spread. Being the counter-party to almost every trade, they'd make profit from always selling above where they were buying. (Except when the price moved quickly -- the downside to this arrangement.) \"\"The spread goes to the market maker\"\" is just stating that the profit implicit in the spread gets consumed by the market maker. With the switch to ECNs, the role of the market maker has changed. For example, ForEx trading firms tend to act as market makers to their customers. On ECNs, the invisible, anonymous guy at the other end of most trades is often a market maker, still performing his traditional role. Yet brokers can interact directly with each other now, rather than relying on the market maker's book. With modern online investing and public order books, retail investors might even be trading directly with each other. Market makers are still out there; in part, they perform a service sold by an Exchange to the companies that choose to be listed on that exchange. That service has changed to helping tamp volatility during normal high-volatility periods (such as at open and close).\"", "title": "" }, { "docid": "149420", "text": "The shift to trading at the close began in 2008. Traders did not want to be caught off guard by surprise news and there was a lot of volatility during the financial crisis, so they would close their position in the evening. Thats how it began. There are two reasons why it sticks around. First, there has been an increase usage of index funds or passive funds. These funds tend to update their positions at the end of the day. From the WSJ: Another factor behind the shift has been the proliferation of passively managed investments, such as index funds. These funds aim to mimic an index, like the S&P 500, by owning the shares that comprise it. Index funds don’t trade as often as active investors, but when they do, it is typically near the market close, traders say. That is because buying or selling a stock at its closing price better aligns their performance with the index they are trying to emulate. The second reason is simply that volume attracts volume. As a result of whats mentioned above, you have a shift to end of day trading, and the corrolary to that is that there is a liquidity shortage from 10am to 3pm. Thus, if you want to buy or sell a stock, but there are few buyers or sellers around, you will significant move the price when you enter your order. Obviously this does not affect retail traders, but imagine hedge funds entering or closing a billion dollar position. It can make a huge impact on price. And one way to mitigate that is to wait until there are more market participants to take the other end of your trade, just as at the end of the day. So this is a self-reinforcing trend that has begun in the markets and will likely stick around. http://www.wsj.com/articles/traders-pile-in-at-the-close-1432768080", "title": "" } ]
5ae156fc5542990adbacf75b	In between Chionodoxa and Aerangis which is a genus of the Orchid family (Orchidaceae)?	[ { "docid": "9167359", "text": "Chionodoxa, known as glory-of-the-snow, is a small genus of bulbous perennial flowering plants in the family Asparagaceae, subfamily Scilloideae, often included in \"Scilla\". The genus is endemic to the eastern Mediterranean, specifically Crete, Cyprus and Turkey. The blue, white or pink flowers appear early in the year making them valuable garden ornamentals. The common name of the genus is based on the habit of flowering in high alpine zones when the snow melts in spring.", "title": "" }, { "docid": "362020", "text": "Aerangis, abbreviated as Aergs in horticultural trade, is a genus of the Orchid family (Orchidaceae). The name of this genus has been derived from the Greek words 'aer' (air) and 'angos' (urn), referring to the form of the lip. It is the type genus of the subtribe Aerangidinae. Approximately 50 species in this genus are known mostly from tropical Africa, but also from the Comoro Islands, Madagascar and Sri Lanka.", "title": "" } ]	[ { "docid": "41164995", "text": "Aerangis is a genus of orchids (Orchidaceae), containing approximately 57 species.", "title": "" }, { "docid": "12861232", "text": "Aerangis gracillima is a species of plant in the Orchidaceae family. It is found in Cameroon and Gabon. Its natural habitat is subtropical or tropical dry forests.", "title": "" }, { "docid": "29504799", "text": "Aerangidinae is classified as a subtribe within the tribe Vandeae in family Orchidaceae. However, it is likely to soon become a synonym of Angraecinae with the genera below re-allocated to this sub-tribe. As traditionally circumscribed, it consists of 36 genera and about 300 species. The type genus of this subtribe is \"Aerangis\". Members of this group are epiphytic orchids having a monopodial habit and are endemic to tropical Africa and Madagascar. They are distinguished from the other subtribes in Vandeae by having an elongate rostellum, an elongate spur, and two pollinia. Most genera in the group indicate pollination by moths, however leaf beetles (family Chrysomelidae) are reported as frequent visitors, but it is unknown whether they are vectors for pollination.", "title": "" }, { "docid": "25891999", "text": "Arthrochilus, commonly called elbow orchids, is a genus of about fifteen species of flowering plants from the orchid family (Orchidaceae) and is found in Australia and New Guinea. The flowers are pollinated by male thynnid wasps which attempt to mate with the flower and are held in place by hooks while the pollinium is transferred between insect and flower.", "title": "" }, { "docid": "10360811", "text": "The genus Platanthera belongs to the subfamily Orchidoideae of the family Orchidaceae, and comprises about 100 species of orchids. The members of this genus, known as the butterfly orchids or fringed orchids, were previously included in the genus \"Orchis\", which is a close relative (along with the genus \"Habenaria\"). They are distributed throughout the temperate regions of the Northern Hemisphere. They are terrestrial and have tubercules.", "title": "" }, { "docid": "25894405", "text": "Pyrorchis, commonly known as beak orchids, is a genus of flowering plants in the orchid family, Orchidaceae and is endemic in Australia. It contains two species which were previously included in the genus \"Lyperanthus\", also known as beak orchids. Both species have fleshy, oval leaves and form colonies which flower profusely after bushfires.", "title": "" }, { "docid": "218068", "text": "Dactylorhiza, commonly called marsh orchid or spotted orchid, is a genus of flowering plants in the orchid family (Orchidaceae). \"Dactylorhiza\" were previously classified under \"Orchis\" which has two round tubers.", "title": "" }, { "docid": "217654", "text": "Vanda is a genus in the orchid family (Orchidaceae), which although not massive (about 80 species), is one of the genera more commonly found in the marketplace. This genus and its allies are considered to be among the most specifically adapted of all orchids within the Orchidaceae. The genus is highly prized in horticulture for its showy, fragrant, long-lasting, and intensely colorful flowers. \"Vanda\" species are widespread across East Asia, Southeast Asia, and New Guinea, with a few species extending into Queensland and some of the islands of the western Pacific. The genus is sometimes abbreviated as\" V.\" in the floral trade.", "title": "" }, { "docid": "25892720", "text": "Genoplesium commonly known as midge orchids, is a genus of about 50 species of flowering plants in the orchid family, Orchidaceae and is found in Australia, New Zealand and New Caledonia. Midge orchids are terrestrial herbs with a single leaf at the base of the plant. They are similar to orchids in the genus \"Prasophyllum\" in that plants without flowers have a hollow, onion-like leaf. The flowers are small but often scented and attractive to their insect pollinators. There is disagreement about which species belong to this genus and some taxonomists suggest that most belong in the genus \"Corunastylis\".", "title": "" }, { "docid": "25893066", "text": "Isotria (fiveleaf orchid) is a genus of flowering plants from the orchid family, Orchidaceae.", "title": "" }, { "docid": "25894310", "text": "Plectorrhiza is a genus of flowering plants from the orchid family, Orchidaceae. It contains three species, all of which are endemic to Australia.", "title": "" }, { "docid": "23209573", "text": "Aerangis citrata is an epiphytic species of orchid indigenous to Madagascar.", "title": "" }, { "docid": "23209616", "text": "Aerangis fastuosa is a species of epiphytic orchid endemic to Madagascar.", "title": "" }, { "docid": "51171692", "text": "Aerangis ellisii is a species of epiphytic orchid. It is native to Madagascar .", "title": "" }, { "docid": "25893887", "text": "Oeceoclades, collectively known as the monk orchids, is a genus of flowering plants from the orchid family, Orchidaceae. It is related to \"Eulophia\" and like that genus is mostly terrestrial in habit. A few species extend into very arid environments, unusual for an orchid.", "title": "" }, { "docid": "363034", "text": "Phragmipedium is a genus of the Orchid family (Orchidaceae) (Subfamily Cypripedioideae) and the only genus comprised in the tribe Phragmipedieae and subtribe Phragmipediinae. The name of the genus is derived from the Greek \"phragma\", which means \"division\", and \"pedium\", which means \"slipper\" (referring to the pouch). It is abbreviated 'Phrag' in trade journals.", "title": "" }, { "docid": "25892249", "text": "Cyanaeorchis is a genus of flowering plants from the orchid family, Orchidaceae. It contains three known species, all of which are endemic to South America.", "title": "" }, { "docid": "23208288", "text": "Aerangis articulata is a species of epiphytic orchid. It is native to Madagascar and the Comoro Islands.", "title": "" }, { "docid": "23209771", "text": "Aerangis modesta is a species of epiphytic orchid native to Madagascar and to the Comoro Islands.", "title": "" }, { "docid": "2911882", "text": "Prosthechea is a genus in the orchid family (Orchidaceae). The name is derived from the Greek word \"prostheke\" (appendix), referring to the appendage on the back of the column. Appendage orchid is a common name for this genus.", "title": "" }, { "docid": "25892901", "text": "Traunsteinera, the round headed orchid, or globe orchid, is a genus of flowering plants from the orchid family, Orchidaceae. There are two known species, native to Europe, Turkey and the Caucasus.", "title": "" }, { "docid": "1317703", "text": "Amitostigma is a genus in the orchid family (Orchidaceae). It is an exclusively Asian genus of 28 orchids, growing in the alpine habitats of China, Japan, Korea, Vietnam, Thailand and the Kuril Islands. Twenty two species of this genus grow in China.", "title": "" }, { "docid": "25893017", "text": "Horvatia is a genus of flowering plants from the orchid family, Orchidaceae. It contains only one known species, Horvatia andicola, which is endemic to Ecuador.", "title": "" }, { "docid": "1154305", "text": "Pleurothallis is a large genus that previously contained about 1240 orchids from the orchid family (Orchidaceae).", "title": "" }, { "docid": "3921449", "text": "Encyclia is an orchid genus with about 170 species. It belongs to the subfamily Epidendroideae of the orchid family (Orchidaceae).", "title": "" }, { "docid": "13200720", "text": "Basiphyllaea is a genus of orchids (family Orchidaceae), known as Carter's orchid or crab orchids. They are native to Florida and the West Indies. At the present time (May 2014), 7 species are recognized:", "title": "" }, { "docid": "53227341", "text": "Caladenia longiclavata, commonly known as the clubbed spider orchid is a species of plant in the orchid family, Orchidaceae and is endemic to the south-west of Western Australia. It is a widespread and common orchid with a single, hairy leaf and one or two greenish-yellow, white and red flowers and which grows in the area between Perth and Albany.", "title": "" }, { "docid": "25893277", "text": "Leporella fimbriata, commonly known as hare orchid or fringed hare orchid, is the only species in the flowering plant genus \"Leporella\" in the orchid family, Orchidaceae and is endemic to the southern Australia mainland. It is related to orchids in the genus \"Caladenia\" but has an unusual labellum and does not have hairy leaves. Its pollination mechanism is also unusual.", "title": "" }, { "docid": "1183972", "text": "Vanilla, the vanilla orchids, forms a flowering plant genus of about 110 species in the orchid family (Orchidaceae). The most widely known member is the flat-leaved vanilla (\"V. planifolia\"), native to Mexico, from which commercial vanilla flavoring is derived. It is the only orchid widely used for industrial purposes in flavoring such products as foods, beverages and cosmetics, and is recognized as the most popular aroma and flavor. The key constituent imparting its popular characteristics is the phenolic aldehyde, vanillin.", "title": "" }, { "docid": "525830", "text": "Cymbidium , or boat orchid, is a genus of 52 evergreen species in the orchid family Orchidaceae. The new Latin genus name is derived from the Latin \"cymba\" meaning boat. Its first known use was in 1815.", "title": "" } ]
4591	How are bonds affected by the Federal Funds Rate?	[ { "docid": "577578", "text": "\"The federal funds rate is one of the risk-free short-term rates in the economy. We often think of fixed income securities as paying this rate plus some premia associated with risk. For a treasury security, we can think this way: (interest rate) = (fed funds rate) + (term premium) The term premium is a bit extra the bond pays because if you hold a long term bond, you are exposed to interest rate risk, which is the risk that rates will generally rise after you buy, making your bond worth less. The relation is more complex if people have expectations of future rate moves, but this is the general idea. Anyway, generally speaking, longer term bonds are exposed to more interest rate risk, so they pay more, on average. For a corporate bond, we think this way: (interest rate) = (fed funds rate) + (term premium) + (default premium) where the default premium is some extra that the bond must pay to compensate the holder for default risk, which is the risk that the bond defaults or loses value as the company's prospects fall. You can see that corporate and government bonds are affected the same way (approximately, this is all hand-waving) by changes in the fed funds rate. Now, that all refers to the rates on new bonds. After a bond is issued, its value falls if rates rise because new bonds are relatively more attractive. Its value rises if rates on new bonds falls. So if there is an unexpected rise in the fed funds rate and you are holding a bond, you will be sad, especially if it is a long term bond (doesn't matter if it's corporate or government). Ask yourself, though, whether an increase in fed funds will be unexpected at this point. If the increase was expected, it will already be priced in. Are you more of an expert than the folks on wall-street at predicting interest rate changes? If not, it might not make sense to make decisions based on your belief about where rates are going. Just saying. Brick points out that treasuries are tax advantaged. That is, you don't have to pay state income tax on them (but you do pay federal). If you live in a state where this is true, this may matter to you a little bit. They also pay unnaturally little because they are convenient for use as a cash substitute in transactions and margining (\"\"convenience yield\"\"). In general, treasuries just don't pay much. Young folk like you tend to buy corporate bonds instead, so they can make money on the default and term premia.\"", "title": "" }, { "docid": "214710", "text": "\"I'll answer your question, but first a comment about your intended strategy. Buying government bonds in a retirement account is probably not a good idea. Government bonds (generally) are tax advantaged themselves, so they offer a lower interest rate than other types of bonds. At no tax or reduced tax, many people will accept the lower interest rate because their effective return may be similar or better depending, for example, on their own marginal tax rate. In a tax-advantaged retirement account, however, you'll be getting the lower interest without any additional benefit because that account itself is already tax-advantaged. (Buying bonds generally may be a good idea or not - I won't comment on that - but choose a different category of bonds.) For the general question about the relationship between the Fed rate and the bond rate, they are positively correlated. There's not direct causal relationship in the sense that the Fed is not setting the bond rate directly, but other interest bearing investment options are tied to the Fed rate and many of those interest-bearing options compete for the same investor dollars as the bonds that you're reviewing. That's at a whole market level. Individual bonds, however, may not be so tightly coupled since the creditworthiness of the issuing entity matters a lot too, so it could be that \"\"bond rates\"\" generally are going up but some specific bonds are going down based on something happening with the issuer, just like the stock market might be generally going up even as specific stocks are dropping. Also keep in mind that many bonds trade as securities on a secondary market much like stocks. So I've talked about the bond rate. The price of the bonds themselves on the secondary market generally move opposite to the rate. The reason is that, for example, if you buy a bond at less than face value, you're getting an effective interest rate that's higher because you get the same sized incremental payments of interest but put less money into the investment. And vice versa.\"", "title": "" } ]	[ { "docid": "285064", "text": "Fundamentally interest rates reflect the time preference people place on money and the things money can buy. If I have a high time preference then I prefer money in my hand versus money promised to me at some date in the future. Thus, I will only loan my money to someone if they offer me an incentive which would be an amount of money to be received in the future that is larger than the amount of money I’m giving the debtor in the present (i.e. the interest rate). Many factors go into my time preference determination. My demand for cash (i.e. my cash balance), the credit rating of the borrower, the length of the loan, and my expectation of the change in currency value are just a few of the factors that affect what interest rate I will loan money. The first loan I make will have a lower interest rate than the last loan, ceteris paribus. This is because my supply of cash diminishes with each loan which makes my remaining cash more valuable and a higher interest rate will be needed to entice me to make additional loans. This is the theory behind why interest rates will rise when QE3 or QEinfinity ever stops. QE is where the Federal Reserve cartel prints new money to purchase bonds from cartel banks. If QE slows or ends the supply of money will stop increasing which will make cash more valuable and higher interest rates will be needed to entice creditors to loan money. Note that increasing the stock of money does not necessarily result in lower interest rates. As stated earlier, the change in value of the currency also affects the interest rate lenders are willing to accept. If the Federal Reserve cartel deposited $1 million everyday into every US citizen’s bank account it wouldn’t take long before lenders demanded very high interest rates as compensation for the decrease in the value of the currency. Does the Federal Reserve cartel affect interest rates? Yes, in two ways. First, as mentioned before, it prints new money that is loaned to the government. It either purchases the bonds directly or purchases the bonds from cartel banks which give them cash to purchase more government bonds. This keeps demand high for government bonds which lowers the yield on government bonds (yields move inverse to the price of the bond). The Federal Reserve cartel also can provide an unlimited amount of funds at the Federal Funds rate to the cartel member banks. Banks can borrow at this rate and then proceed to make loans at a higher rate and pocket the difference. Remember, however, that the Federal Reserve cartel is not the only market participant. Other bond holders, such as foreign governments and pension funds, buy and sell US bonds. At some point they could demand higher rates. The Federal Reserve cartel, which currently holds close to 17% of US public debt, could attempt to keep rates low by printing new money to buy all existing US bonds to prevent the yield on bonds from going up. At that point, however, holding US dollars becomes very dangerous as it is apparent the Federal Reserve cartel is just a money printing machine for the US government. That’s when most people begin to dump dollars en masse.", "title": "" }, { "docid": "594667", "text": "\"In the United States, if someone refers to the \"\"interest rate\"\", especially if heard on news or talk radio in particular, they are almost always referring to the federal funds rate, a rate set forth and maintained by the United States Federal Reserve (the \"\"fed\"\" for short). If the fed opts to raise or lower this rate, it subsequently effects all interest rates, whether by being directly connected in a chain of loans or by market demand through the efficiency of financial markets in the case of bond auctions. The FOMC meets eight times each year to determine the target for the federal funds rate. The federal funds rate effects all interest rates because it is the originating rate of interest on all loans in the chain of loans. Because of this significance as a benchmark for all interest rates, it is the rate most commonly referred to as \"\"interest rate\"\" when used alone. That is why other rates are specified by what they actually are; e.g., mortgage rates; 10 year & 30 year (for 10 year treasury and 30 year treasury bond yields respectively); savings rate, auto rate, credit card rate, CD rate—all rates of interest effected by the originating loan that is the federal funds rate. This is true in the United States but will vary for other countries. In general though, it will almost always refer to the originating rate for all loans in a given country, institution, etc. Note that bonds have yields that are based on market demand that is, in turn, based on the federal funds rate. It is because of the efficiency of financial markets that the demand, and thus the yields, are correlated to the federal funds rate.\"", "title": "" }, { "docid": "455398", "text": "Sounds like a bad idea. The IRA is built on the power of compounding. Removing contributions will hurt your retirement savings, and you will never be able to make that up. Instead, consider tax-free investments. State bonds, Federal bonds, municipal bonds, etc. For example, I invest in California muni bonds fund which gives me ~3-4% annual dividend income - completely tax free. In addition - there's capital appreciation of your fund holdings. There are risks, of course, for example rate changes will affect yields and capital appreciation, so consult with someone knowledgeable in this area (or ask another question here, for the basics). This will give you the same result as you're expecting from your Roth IRA trick, without damaging your retirement savings potential.", "title": "" }, { "docid": "599436", "text": "\"1. Interest rates What you should know is that the longer the \"\"term\"\" of a bond fund, the more it will be affected by interest rates. So a short-term bond fund will not be subject to large gains or losses due to rate changes, an intermediate-term bond fund will be subject to moderate gains or losses, and a long-term bond fund will be subject to the largest gains or losses. When a book or financial planner says to buy \"\"bonds\"\" with no other qualification, they almost always mean investment-grade intermediate-term bond funds (or for individual bonds, the equivalent would be a bond ladder averaging an intermediate term). If you want technical details, look at the \"\"average duration\"\" or \"\"average maturity\"\" of the bond fund; as a rough guide, if the duration is 10, then a 1% change in interest rates would be a 10% gain or loss on the fund. Another thing you can do is look at long-term (10 years or ideally longer) performance history on some short, intermediate, and long term bond index funds, and you can see how the long term funds bounced around more. Non-investment-grade bonds (aka junk bonds or high yield bonds) are more affected by factors other than interest rates, including some of the same factors (economic booms or recessions) that affect stocks. As a result, they aren't as good for diversifying a portfolio that otherwise consists of stocks. (Having stocks, investment grade bonds, and also a little bit in high-yield bonds can add diversification, though. Just don't replace your bond allocation with high-yield bonds.) A variety of \"\"complicated\"\" bonds exist (convertible bonds are an example) and these are tough to analyze. There are also \"\"floating rate\"\" bonds (bank loan funds), these have minimal interest rate sensitivity because the rate goes up to offset rate rises. These funds still have credit risks, in the credit crisis some of them lost a lot of money. 2. Diversification The purpose of diversification is risk control. Your non-bond funds will outperform in many years, but in other years (say the -37% S&P 500 drop in 2008) they may not. You will not know in advance which year you'll get. You get risk control in at least a few ways. There's also an academic Modern Portfolio Theory explanation for why you should diversify among risky assets (aka stocks), something like: for a given desired risk/return ratio, it's better to leverage up a diverse portfolio than to use a non-diverse portfolio, because risk that can be eliminated through diversification is not compensated by increased returns. The theory also goes that you should choose your diversification between risk assets and the risk-free asset according to your risk tolerance (i.e. select the highest return with tolerable risk). See http://en.wikipedia.org/wiki/Modern_portfolio_theory for excruciating detail. The translation of the MPT stuff to practical steps is typically, put as much in stock index funds as you can tolerate over your time horizon, and put the rest in (intermediate-term investment-grade) bond index funds. That's probably what your planner is asking you to do. My personal view, which is not the standard view, is that you should take as much risk as you need to take, not as much as you think you can tolerate: http://blog.ometer.com/2010/11/10/take-risks-in-life-for-savings-choose-a-balanced-fund/ But almost everyone else will say to do the 80/20 if you have decades to retirement and feel you can tolerate the risk, so my view that 60/40 is the max desirable allocation to stocks is not mainstream. Your planner's 80/20 advice is the standard advice. Before doing 100% stocks I'd give you at least a couple cautions: See also:\"", "title": "" }, { "docid": "118817", "text": "Federal Funds Rate The interest rate at which a depository institution lends funds maintained at the Federal Reserve to another depository institution overnight. The federal funds rate is generally only applicable to the most creditworthy institutions when they borrow and lend overnight funds to each other. The federal funds rate is one of the most influential interest rates in the U.S. economy, since it affects monetary and financial conditions, which in turn have a bearing on key aspects of the broad economy including employment, growth and inflation. http://www.investopedia.com/terms/f/federalfundsrate.asp#ixzz3mB5kCtvT", "title": "" }, { "docid": "585269", "text": "\"(Since you used the dollar sign without any qualification, I assume you're in the United States and talking about US dollars.) You have a few options here. I won't make a specific recommendation, but will present some options and hopefully useful information. Here's the short story: To buy individual stocks, you need to go through a broker. These brokers charge a fee for every transaction, usually in the neighborhood of $7. Since you probably won't want to just buy and hold a single stock for 15 years, the fees are probably unreasonable for you. If you want the educational experience of picking stocks and managing a portfolio, I suggest not using real money. Most mutual funds have minimum investments on the order of a few thousand dollars. If you shop around, there are mutual funds that may work for you. In general, look for a fund that: An example of a fund that meets these requirements is SWPPX from Charles Schwabb, which tracks the S&P 500. Buy the product directly from the mutual fund company: if you go through a broker or financial manager they'll try to rip you off. The main advantage of such a mutual fund is that it will probably make your daughter significantly more money over the next 15 years than the safer options. The tradeoff is that you have to be prepared to accept the volatility of the stock market and the possibility that your daughter might lose money. Your daughter can buy savings bonds through the US Treasury's TreasuryDirect website. There are two relevant varieties: You and your daughter seem to be the intended customers of these products: they are available in low denominations and they guarantee a rate for up to 30 years. The Series I bonds are the only product I know of that's guaranteed to keep pace with inflation until redeemed at an unknown time many years in the future. It is probably not a big concern for your daughter in these amounts, but the interest on these bonds is exempt from state taxes in all cases, and is exempt from Federal taxes if you use them for education expenses. The main weakness of these bonds is probably that they're too safe. You can get better returns by taking some risk, and some risk is probably acceptable in your situation. Savings accounts, including so-called \"\"money market accounts\"\" from banks are a possibility. They are very convenient, but you might have to shop around for one that: I don't have any particular insight into whether these are likely to outperform or be outperformed by treasury bonds. Remember, however, that the interest rates are not guaranteed over the long run, and that money lost to inflation is significant over 15 years. Certificates of deposit are what a bank wants you to do in your situation: you hand your money to the bank, and they guarantee a rate for some number of months or years. You pay a penalty if you want the money sooner. The longest terms I've typically seen are 5 years, but there may be longer terms available if you shop around. You can probably get better rates on CDs than you can through a savings account. The rates are not guaranteed in the long run, since the terms won't last 15 years and you'll have to get new CDs as your old ones mature. Again, I don't have any particular insight on whether these are likely to keep up with inflation or how performance will compare to treasury bonds. Watch out for the same things that affect savings accounts, in particular fees and reduced rates for balances of your size.\"", "title": "" }, { "docid": "320790", "text": "Lowering of the US credit rating would affect all US bonds. Some institutional investments are required to invest in securities with a certain credit rating (i.e. money markets and some low risk mutual funds). If the credit rating is lowered these institutions would be required to dump their US bond holdings. This could have a serious affect on bond prices. The lower bond prices would drive up yields. If the US credit rating was lowered after you purchased TIPS then the price you could sell your TIPS for would most probably be lower then what you bought them. You would lose money. All US bonds, including TIPS, would be affected by a lower credit rating since the credit rating is suppose to indicate the borrower's ability to repay the debt. This is independent of inflation. TIPS provide no additional benefit over regular bonds in regard to credit rating.", "title": "" }, { "docid": "372657", "text": "\"Let's talk interest rates on your junk bonds. Even after all that the US has been through (and is still going through), the United States dollar is widely regarded as one of the safest safe havens for your money. As such it serves as a de facto baseline against which all other investments can be measured, the bar everyone has to pass: if you could earn 4% on a 5-year US Treasury bond, or earn 4% on anything else over the next 5 years, you pick the Treasury bond. In many ways this means that the interest rate on a Treasury bond is the closest single measure we have to the price of money all by itself. If someone is loaning you money, they could be loaning it to the Treasury instead; they are losing out by making this loan to you, and must charge you at least this rate just to break even. But most people/governments/countries aren't as credit-worthy as the US Treasury. A few are (the US treasury isn't magical, after all, just really good at what it does), but generally they are not. There is a possibility when loaning money to these entities that you will not get your money back. That is risk. All entities have some risk (even the US treasury!), and some have more than others; \"\"junk bonds\"\" have a somewhat elevated level of this risk. Now, you don't just take a risk on for free (unless you're being charitable or something, but I hope you can find better beneficiaries of charity than the average junk bond). You need to be compensated for that risk. Lenders will demand compensation commensurate with that risk - or they will just walk away without making any loans or buying any bonds because it's not worth it. The difference between the interest rate on a US Treasury bond and the interest rate on another bond, such as a junk bond, is the risk premium - the cost of carrying that risk. Therefore you can see that the interest rate on a junk bond is the price of money plus the risk premium. Now, the Federal Reserve adjusts the price of money from time to time, by buying and selling US Treasury bonds until the price is something they like. This means that one component of interest rate on a junk bond is the interest rate on the US Treasury bond, and it is effectively controlled by the Federal Reserve (through that layer of indirection). The other component of the interest rate on a junk bond is the risk premium. It's not generally possible to know in advance whether or not some company will actually default. People have to guess, and decide how comfortable they are taking that risk. This means that risk is more expensive (and interest rates are higher) when they think the companies in question are going through some hard times, and risk will also be more expensive when people decide that they can't take as many risks (perhaps they've already lost some money and need to take additional steps to protect the rest). It's definitely very hard for an individual to decide what the risk on a particular bond is. The good news is that you generally don't have to. There are a bunch of rich jerks, hedge funds, retirement funds, insurance companies, and other investment entities out there who spend all day looking at things like bonds, trying to estimate the risk. Their willingness to exploit minuscule differences between the interest rate on a bond and the real risk means that the average bond on the market will be fairly priced, according to what all those people think. Plenty of them can still be wrong, mind you (cf. mortgage-backed securities) but in the general case the price of any security reflects all the information everyone in the world has on it on average, so if you're wrong you're in good company. When you buy a nice diversified bond fund, you have access to a bunch of bonds at a pretty-standard price. So that's interest rates for you. But you asked about prices. As it turns out, they're the same thing! - just expressed slightly differently. One way or another a bond is essentially meant to be a stream of payments worth a certain amount in the end - this is why you'll hear them referred to sometimes as a \"\"fixed-income security\"\". The interest rate is essentially the difference between the price you pay now, and the value you receive later, except expressed as a rate. Technically, you could structure the bonds differently (e.g. does the bond pay little bits of interest as you go along, or just pay one big lump sum in the end?) but you can use Math to convert between these two situations, and figure out how much money is worth which when, so it doesn't really matter. Anyway. This means that rising interest rates means lower bond prices on bonds you already own (and falling interest rates means higher bond prices). So if the Federal Reserve increases interest rates, the face value of your bond funds will fall. Also, if people think that the companies issuing the bonds are too risky, the face value of those bonds will also fall. (You were probably expecting the latter effect, though.) Mind you, you will still get the same amount of future money out of them as you would otherwise: that's why they're fixed-income securities. However, a higher interest rate means \"\"I can get more money in the future for less money now\"\", and so people will be willing to pay you less for your bond in the present. This is known as interest rate risk. It is higher on longer term bonds, because those have more time to earn interest.\"", "title": "" }, { "docid": "388391", "text": "\"So \"\"Operation Twist\"\" is actually a pretty simple concept. Here's the break down: The Fed sells short-term treasury bonds that it already holds on its books. Short-term treasury bonds refer to - bonds that mature in less than three years. Then: Uses that money to buy long term treasury bonds. Long-term treasury bonds refer to - bonds that mature in six to 30 years The reason: The fed buys these longer-term treasuries to lower longer-term interest rates and encourage more borrowing and spending. Diving deeper into how it works: So the Fed can easily determine short-term rates by using the Federal funds rate this rate has a direct effect on the following: However this does not play a direct role in influencing the rate of long-term loans (what you might pay on a 30-year fixed mortgage). Instead, long-term rates are determined by investors who buy and sell bonds in the bond market, which changes daily. These bond yields fluctuate depending on the health of the economy and inflation. However, the Fed funds rate does play an indirect role in these rates. So now that we know a little more about what effects what rate, why does lower long-term rates in treasuries influence my 30yr fixed mortgage? Well when you are looking for a loan you are entering a market and competing against other people, by people I mean anyone looking for money (e.g: my grandmother, companies, or the US government). The bank that lends you money has to decide weather the deal you are offering them is better then another deal on the market. If the risk of lending to one person is the same as the risk of lending to another, the bank will make whichever loan yields the higher interest rate. The U.S. government is considered a very safe borrower, so much so that government bonds are considered almost “risk free”, but because of the lower risk the rate of return is lower. So now the bank has to factor in this risk and make its decision weather to lend you money, or the government. So, if the government were to go to the market and buy its own long-term bonds it is adding demand in the market causing the price of the bond to rise in effect lowering the interest rate (when price goes up, yield goes down). So when you go back and ask for a loan it has to re-evaluate and decide \"\"Is it worth giving this money to Joe McFreeBeer instead and collecting a higher yield?\"\" (After all, Joe McFreeBeer is a nice guy). Here's an example: Lets say the US has a rating of 10 out of 10 and its bonds pay a 2% yield. Now lets say for each lower mark in rating the bank will lend at a minimum of 1% higher and your rating is 8 of 10. So if you go to market, the lowest rate you can get will be 4%. Now lets say price rises on the US treasury and causes the rate to go down by 1%. In this scenario you will now be able to get a loan for 3% and someone with a rating of 7 of 10 would be able to get that 4% loan. Here's some more info and explinations: Why is the Government Buying Long-Term Bonds? What Is 'Operation Twist'? A Q&A on US Fed Program Federal Reserve for Beginners Federal Open Market Committee\"", "title": "" }, { "docid": "567749", "text": "The US Treasury is not directly/transactionally involved, but can affect the junk bond market by issuing new bonds when rates rise. Since US bonds are considered completely safe, changes in yield will affect low quality debt. For example, if rates rose to levels like 1980, a 12% treasury bond would drive the prices of junk bonds issued today dramatically lower. Another price factor is likelihood of default. Companies with junk credit ratings have lousy balance sheets, so negative economic conditions or tight short term debt markets can result in default for many of these companies. Whether bonds in a fund are new issues or purchased on the secondary market isn't something that is very relevant to the individual investor. The current interest rate environment is factored into the market already via prices of bonds.", "title": "" }, { "docid": "144177", "text": "\"If you owned a bank how would you invest the bank's money? Typically banks are involved in loaning out money to businesses, people, and government at a higher interest rate then what they are paying to depositors. This is the spread and how they make money. If the bank determines that the yields on government bonds is more attractive then loaning the money out to businesses and people then the bank will purchase government bonds. It can also decide the other way. In this manner the mortgage and bond markets are always competing for capital and tend to offer very similar yields. Certain banks have the unique privilege of being able to borrow money from the FED at the Federal Funds rate and use this money to purchase government debt or loan it out to other banks or purchase other debt products. In this manner you see a high correlation between the FED funds rate, mortgage rates, and treasury yields. Other political factors include legislation that encourages mortgage lending (see Community Reinvestment Act) where banks may not have made the loans without said legislation. In short, keep your eye on the FED and ask yourself: \"\"Does the FED want rates to rise?\"\" and \"\"Can the US government afford rising rates?\"\" The answer to these two questions is no. However, the FED may be pressured to \"\"stop the presses\"\" if inflation becomes unwieldy and the FED actually starts to care about food and energy prices. So far this hasn't been the case.\"", "title": "" }, { "docid": "10558", "text": "\"At the most fundamental level, every market is comprised of buyers and selling trading securities. These buyers and sellers decide what and how to trade based on the probability of future events, as they see it. That's a simple statement, but an example demonstrates how complicated it can be. Picture a company that's about to announce earnings. Some investors/traders (from here on, \"\"agents\"\") will have purchased the company's stock a while ago, with the expectation that the company will have strong earnings and grow going forward. Other agents will have sold the stock short, bought put options, etc. with the expectation that the company won't do as well in the future. Still others may be unsure about the future of the company, but still expecting a lot of volatility around the earnings announcement, so they'll have bought/sold the stock, options, futures, etc. to take advantage of that volatility. All of these various predictions, expectations, etc. factor into what agents are bidding and asking for the stock, its associated derivatives, and other securities, which in turn determines its price (along with overall economic factors, like the sector's performance, interest rates, etc.) It can be very difficult to determine exactly how markets are factoring in information about an event, though. Take the example in your question. The article states that if market expectations of higher interest rates tightened credit conditions... In this case, lenders could expect higher interest rates in the future, so they may be less willing to lend money now because they expect to earn a higher interest rate in the future. You could also see this reflected in bond prices, because since interest rates are inversely related to bond prices, higher interest rates could decrease the value of bond portfolios. This could lead agents to sell bonds now in order to lock in their profits, while other agents could wait to buy bonds because they expect to be able to purchase bonds with a higher rate in the future. Furthermore, higher interest rates make taking out loans more expensive for individuals and businesses. This potential decline in investment could lead to decreased revenue/profits for businesses, which could in turn cause declines in the stock market. Agents expecting these declines could sell now in order to lock in their profits, buy derivatives to hedge against or ride out possible declines, etc. However, the current low interest rate environment makes it cheaper for businesses to obtain loans, which can in turn drive investment and lead to increases in the stock market. This is one criticism of the easy money/quantitative easing policies of the US Federal Reserve, i.e. the low interest rates are driving a bubble in the stock market. One quick example of how tricky this can be. The usual assumption is that positive economic news, e.g. low unemployment numbers, strong business/residential investment, etc. will lead to price increases in the stock market as more agents see growth in the future and buy accordingly. However, in the US, positive economic news has recently led to declines in the market because agents are worried that positive news will lead the Federal Reserve to taper/stop quantitative easing sooner rather than later, thus ending the low interest rate environment and possibly tampering growth. Summary: In short, markets incorporate information about an event because the buyers and sellers trade securities based on the likelihood of that event, its possible effects, and the behavior of other buyers and sellers as they react to the same information. Information may lead agents to buy and sell in multiple markets, e.g. equity and fixed-income, different types of derivatives, etc. which can in turn affect prices and yields throughout numerous markets.\"", "title": "" }, { "docid": "548971", "text": "Mortgage rates generally consist of two factors: The risk premium is relatively constant for a particular individual / house combination, so most of the changes in your mortgage rate will be associated with changes in the price of money in the world economy at large. Interest rates in the overall economy are usually tied to an interest rate called the Federal Funds rate. The Federal Reserve manipulates the federal funds rate by buying and/or selling bonds until the rate is something they like. So you can usually expect your interest rate to rise or fall depending on the policies of the Federal Reserve. You can predict this in a couple of ways: The way they have described their plans recently indicates that will keep interest rates low for an extended period of time - probably through 2014 or so - and they hope to keep inflation around 2%. Unless inflation is significantly more than 2% between now and then, they are extremely unlikely to change that plan. As such, you should probably not expect mortgage interest rates in general to change more than infinitesimally small amounts until 2014ish. Worry more about your credit score.", "title": "" }, { "docid": "428913", "text": "Distributions of interest from bonds are taxable as income by the Federal, state and municipal (if applicable) government. End of year fund distributions are subject to capital gains taxes as well. You can minimize taxation by: Note that the only bonds that are guaranteed safe are US Government obligations, as the US government has unlimited taxation powers and the ability to print money. Municipal obligations are generally safe, but there is a risk that municipal governments will default. You can also avoid taxation by not realizing gains. If you buy individual stocks or tax-efficient mutual funds, you will have minimal tax liability until you sell. Also, just wanted to point out that bonds do not equal safety and money markets do not pay sufficient interest to offset inflation, you need a diversified portfolio. Five year treasury notes are only paying 1.3% now, and bond prices drop when interest rates go up. Given the level of Federal spending and the wind-down of the war, its likely that rates will rise.", "title": "" }, { "docid": "481312", "text": "\"A bond fund will typically own a range of bonds of various durations, in your specific fund: The fund holds high-quality long-term New York municipal bonds with an average duration of approximately 6–10 years So through this fund you get to own a range of bonds and the fund price will behave similar to you owning the bonds directly. The fund gives you a little diversification in terms of durations and typically a bit more liquidity. It also may continuously buy bonds over time so you get some averaging vs. just buying a bond at a given time and holding it to maturity. This last bit is important, over long durations the bond fund may perform quite differently than owning a bond to maturity due to this ongoing refresh. Another thing to remember is that you're paying management fees for the fund's management. As with any bond investment, the longer the duration the more sensitive the price is to change in interest rates because when interest rates change the price will track it. (i.e. compare a change of 1% for a one year duration vs. 1% yearly over 10 years) If I'm correct, why would anyone in the U.S. buy a long-term bond fund in a market like this one, where interest rates are practically bottomed out? That is the multi-trillion dollar question. Bond prices today reflect what \"\"people\"\" are willing to pay for them. Those \"\"people\"\" include the Federal Reserve which through various programs (QE, Operate Twist etc.) has been forcing the interest rates to where they want to see them. If no one believed the Fed would be able to keep interest rates where they want them then the prices would be different but given that investors know the Fed has access to an infinite supply of money it becomes a more difficult decision to bet against that. (aka \"\"Don't fight the Fed\"\"). My personal belief is that rates will come up but I haven't been able to translate that belief into making money ;-) This question is very complex and has to do not only with US policies and economy but with the status of the US currency in the world and the world economy in general. The other saying that comes to mind in this context is that the market can remain irrational (and it certainly seems to be that) longer than you can remain solvent.\"", "title": "" }, { "docid": "144077", "text": "Banks cannot just borrow from the Federal Reserve and use that money to make loans. The first thing you need to understand is how fractional reserve banking works. The banks can make loans with money that their customers have deposited in their accounts. The interest and fees from those loans go to pay the salaries of those working at the banks with leftover profit to pay dividends (interest on your bank accounts). The only reason that the Federal Reserve allows overnight lending is so that banks don't immediately become insolvent if they have larger than usual withdrawals by their depositors. The Federal Reserve keeps an eye on the balance sheets of the banks that are doing the borrowing, and if they didn't have assets in the form of deposits, they would force the banks to sell the loans that were made from those deposits. What does this have to do with personal finance? I think this question is only marginally on-topic here. This amount of money in circulation is affected specifically by the fraction of the money that can be used for making other loans. But the bigger influence is the rate that the Federal Reserve charges for overnight lending. They raise and lower the rates which affects the rates that the banks can lend at while remaining profitable.", "title": "" }, { "docid": "110856", "text": "No, they do not. Stock funds and bonds funds collect income dividends in different ways. Stock funds collect dividends (as well as any capital gains that are realized) from the underlying stocks and incorporates these into the funds’ net asset value, or daily share price. That’s why a stock fund’s share price drops when the fund makes a distribution – the distribution comes out of the fund’s total net assets. With bond funds, the internal accounting is different: Dividends accrue daily, and are then paid out to shareholders every month or quarter. Bond funds collect the income from the underlying bonds and keep it in a separate internal “bucket.” A bond fund calculates a daily accrual rate for the shares outstanding, and shareholders only earn income for the days they actually hold the fund. For example, if you buy a bond fund two days before the fund’s month-end distribution, you would only receive two days’ worth of income that month. On the other hand, if you sell a fund part-way through the month, you will still receive a partial distribution at the end of the month, pro-rated for the days you actually held the fund. Source Also via bogleheads: Most Vanguard bond funds accrue interest to the share holders daily. Here is a typical statement from a prospectus: Each Fund distributes to shareholders virtually all of its net income (interest less expenses) as well as any net capital gains realized from the sale of its holdings. The Fund’s income dividends accrue daily and are distributed monthly. The term accrue used in this sense means that the income dividends are credited to your account each day, just like interest in a savings account that accrues daily. Since the money set aside for your dividends is both an asset of the fund and a liability, it does not affect the calculated net asset value. When the fund distributes the income dividends at the end of the month, the net asset value does not change as both the assets and liabilities decrease by exactly the same amount. [Note that if you sell all of your bond fund shares in the middle of the month, you will receive as proceeds the value of your shares (calculated as number of shares times net asset value) plus a separate distribution of the accrued income dividends.]", "title": "" }, { "docid": "400646", "text": "\"Can it be so that these low-interest rates cause investors to take greater risk to get a decent return? With interest rates being as low as they are, there is little to no risk in banking; especially after Dodd-Frank. \"\"Risk\"\" is just a fancy word for \"\"Will I make money in the near/ long future.\"\" No one knows what the actual risk is (unless you can see into the future.) But there are ways to mitigate it. So, arguably, the best way to make money is the stock market, not in banking. There is a great misallocation of resources which at some point will show itself and cause tremendous losses, even maybe cause a new financial crisis? A financial crisis is backed on a believed-to-be strong investment that goes belly-up. \"\"Tremendous Losses\"\" is a rather grand term with no merit. Banks are not purposely keeping interest rates low to cause a financial crisis. As the central banks have kept interest rates extremely low for a decade, even negative, this affects how much we save and borrow. The biggest point here is to know one thing: bonds. Bonds affect all things from municipalities, construction, to pensions. If interest rates increased currently, the current rate of bonds would drop vastly and actually cause a financial crisis (in the U.S.) due to millions of older persons relying on bonds as sources of income.\"", "title": "" }, { "docid": "117875", "text": "If you are in an economy which has a decent liquid debt market (corporate bonds, etc.), then you may look into investing in AA or AA+ rated bonds. They can provide higher returns than bank deposits and are virtually risk-free. (Though in severe economic downturns, you can see defaults in even very high-rated bonds, leading to partial or complete loss of value however, this is statistically quite rare). You can make this investment through a debt mutual fund but please make sure that you read through the offer document carefully to understand the investment style of the mutual fund and their expense ratio (which directly affect your returns). In any case, it is always recommended to reach out to an investment adviser who is good with local tax laws to minimize taxes and maximize returns.", "title": "" }, { "docid": "159336", "text": "\"To try and address your 'how' it goes a bit like this. You need to first assess how your stuff is invested, if for example half is in stocks, and the other half is in bonds, then you will need to calculate a 'blended' rate for what are reasonable 'average return' for both. That might mean looking at the S&P500 or Russell 3000 for the stock portion, and some bond index for that portion, then 'blend the rates', in this case using a formula like this then compare the blended rate with the return in your IRA. It is generally a lot more useful to compare the various components of your total return separately, especially if you investing with a particular style such as 'agressive growth' or you are buying actual bonds and not a bond fund since most of the bond oriented indexes are for bond funds, which you can't really compare well with buying and holding bonds to maturity. Lets say your stock side was two mutual funds with different styles, one 'large cap' the other 'aggressive growth'. In that case you might want to compare each one of those funds with an appropriate index such as those provided by Morningstar If you find one of them is consistently below the average, you might want to consider finding an alternative fund who's manager has a better track record (bearing in mind that \"\"past performance....\"\") For me (maybe someone has a good suggestion here) bonds are the hard thing to judge. The normal goal of actually owning bonds (as opposed to a fund) is to retain the entire principal value because there's no principal fluctuation if you hold the bond to maturity (as long as you choose well and the issuer doesn't default) The actual value 'right now' of a bond (as in selling before maturity) and bond funds, goes up and down in an inverse relationship with interest rates. That means the indexes for such things also go up and down a lot, so it's very hard to compare them to a bond you intend to hold to maturity. Also, for such a bond, there's not a lot of point to 'switch out' unless you are worried about the issuer defaulting. If rates are up from what you are getting on your bonds, then you'll have to sell your bond at a discount, and all that happens is you'll end up holding a different bond that is worth less, but has higher interest (basically the net return is likely to be pretty much the same). The better approach there is generally to 'ladder' your maturity dates so you get opportunities to reinvest at whatever the prevailing rates are, without having to sell at a discount.. anyway the point is that I'm not sure there's a lot of value to comparing return on the bond portion of an IRA unless it's invested in bond funds (which a lot of people wanting to preserve principal tend to avoid)\"", "title": "" }, { "docid": "317667", "text": "Sure thing - Treasuries Bonds/Bills are what the US Gov uses to borrow. However it's slightly different than taking out a loan. It's basically an agreement to give (repay) a set sum of money at a certain time in the future in exchange for a sum of funding that's determined by market forces (supply & demand). The difference between today's price and the payment in the future is the interest. For example (completely made up numbers): - Today is 08/05/2017 - The government issues a bond that say it will pay who ever owns this bond $105 on 08/05/2018 - The market decides that $105 from the US government paid a year from now is worth $100 today. In other words the US Government is borrowing for one year at a rate of 5% (105 - 100) / 100 = .05 = 5% Now consider Saudi Arabia's petroleum company, Aramco. Because petroleum is traded in dollars, when Aramco makes a sale, its paid in USD. Some of that is going to be reinvested into the company, some paid out in dividends to share holders but inevitably some of that will be saved someplace where it can make interest. Because treasuries are traded/issued in dollars and because Aramco's businesses deals primarily in dollars, treasuries are the natural place to store that savings, especially because the market considers them extremely safe. If they exchange the USD into the Saudi currency to store the money in Saudi assets, Aramco is subject to exchange rate risk. If the riyal depreciates relative to the dollar, Aramco will lose wealth on the exchange back to dollars when they go to move those funds back into their business. It's in their interest to deal with assets denominated in USD (i.e. T-Bonds) in order to avoid this. So now because the Saudis want T-Bonds as well, the additional demand pushes the market price of our bond from $100 to $102. And the effective one year borrowing rate for the Government goes from 5% to 2.9%. (105 - 102)/102 = .029411 = 2.9% And there you have it, cheaper borrowing. It's also worth noting how this encourages business around the world to deal in dollars which are directly controlled by the federal reserve. This makes the US's position extremely powerful.", "title": "" }, { "docid": "406325", "text": "If your mortgage interest is tax-deductible, it's generally a bad idea to pay down the principal on the mortgage because you'd be losing the tax deduction. You could instead invest it in a tax-free municipal bond fund, especially if you're in a high tax bracket (including state and local marginal tax rates). For example, if you have a 5% rate mortgage on your home, you could invest in a 3.5% municipal bond and still come out ahead when you apply the tax deduction to your income at a 44% (33% federal + 7% state + 4% city in NYC) marginal tax rate.", "title": "" }, { "docid": "446214", "text": "\"What is a bond price? A bond is an asset, and like any tradeable asset it has a price. If I hold $10K face value of a certain GM bond, then I would be willing to sell it at some price, which may be more or less than $10K. Whoever is willing to sell it for the lowest amount determines the price. The price is determined by the market, just as all prices are. It's what you can sell a bond for. Bond prices may be quoted in various funny ways, like as a discount or premium relative to the face value or as a premium over a treasury, but at the end it all should be converted to how much you have to pay today. In this case, it's how much you would pay today to get a set of future coupon and principal payments. What is Yield to Maturity? A bond is a contract entitling you to a certain set of predefined cash flows. If you take that set of cash flows and discount them using a single rate at all maturities such that the discounted value is equal to the price, the single rate you have identified is the YTM. Mathematically, this is the same as finding the IRR (internal rate of return) of some set of cash flows. In this case the cash flows are the coupons and principal repayment. Other bond concepts. Note that the other aspects of a bond, like maturity, coupon rate, and face value, are immutably written into the bond contract. All they do is define what payments the bond entitles the owner to. They don't say how much someone would pay today in order to be entitled to those payments. One can't know how much a future payment is worth without discounting. If you know the appropriate discount rate at every relevant maturity, you could calculate the fair price of a bond. That's the other direction. YTM looks at the market price and associated cash flows and imputes what single discount rate would make that price fair. What is YTM good for? Recall what I said about IRR above. Why would anyone want to know what discount rate equates the cash flows of a project to its cost? Because it's an easy way to summarize how profitable the project is expected to be. YTM is a quick way to summarize the yield one would get on a bond if they were to buy it today and hold to maturity. If one bond has a higher YTM than another, than heuristically we believe it pays out more and should be associated with greater risk if the market is working properly. It can be used to compare bonds or to look at how changes in bond prices are affecting expected yields. Ask yourself, how would you compare two different bonds with different maturities and coupon rates? Which one is riskier or more profitable? The simplest way to summarize this information is with the yield to maturity. YTM is used frequently enough that when you just say a bond's \"\"yield,\"\" people will assume you are talking about its yield to maturity. What is YTM not good for? One thing to be wary of is using YTM as a discount rate. It looks like a discount rate but it works for that bond and that bond only. In reality each individual coupon payment has a true discount rate, and the discount rate at each horizon is different from each other horizon. Those are true discount rates that can be applied to any cash flow of similar risk to get the right price. We can think of YTM as some kind of average of those discount rates that produces the correct price for that bond only. You should never use it for discounting something else.\"", "title": "" }, { "docid": "596511", "text": "How is that the federal reserve's fault? federal reserve's only tools are interest rates, loans, and buying/selling of bonds. To blame fed reserve for jobs is like blaming a car for not being able to fly. That's the job of an airplane. Meaning, jobs are a problem of the federal government fiscal policies, and NOT monetary policies.", "title": "" }, { "docid": "269055", "text": "First off, I do not recommend buying individual bonds yourself. Instead buy a bond fund (ETF or mutual fund). That way you get some diversification. The risk-reward ratio will be evident in what you find to invest in. Junk bond funds pay the highest rates. Treasury bond funds pay the lowest. So you have to ask yourself how comfortable are you with risk? Buy the funds that pay the highest rate but still let you sleep at night.", "title": "" }, { "docid": "182055", "text": "This directly relates to the ideas behind the yield curve. For a detailed explanation of the yield curve, see the linked answer that Joe and I wrote; in short, the yield curve is a plot of the yield on Treasury securities against their maturities. If short-term Treasuries are paying higher yields than long-term debt, the yield curve has a negative slope. There are a lot of factors that could cause the yield curve to become negatively sloped, or at least less steep, but in this case, oil prices and the effective federal funds rate may have played a significant role. I'll quote from the section of the linked answer that describes the effect of oil prices first: a rise in oil prices may increase expectations of short-term inflation, so investors demand higher interest rates on short-term debt. Because long-term inflation expectations are governed more by fundamental macroeconomic factors than short-term swings in commodity prices, long-term expectations may not rise nearly as much as short term expectations, which leads to a yield curve that is becoming less steep or even negatively sloped. As the graph shows, oil prices increased dramatically, so this increase may have increased expectations of short-term inflation expectations substantially. The other answer describes an easing of monetary policy, e.g. a decrease in the effective federal funds rate (FFR), as a factor that could increase the slope of the yield curve. However, a tightening of monetary policy, e.g. an increase in the FFR, could decrease the slope of the yield curve because a higher FFR leads investors to demand a higher rate of return on shorter-term securities. Longer-term Treasuries aren't as affected by short-term monetary policy, so when short-term yields increase more than long-term yields, the yield curve becomes less steep and/or negatively sloped. The second graph shows the effective federal funds rate for the period in question, and once again, the increase is significant. Finally, look at a graph of inflation for the relevant period. Intuitively, the steady increase in inflation from 1975 onward may have increased investors expectations of short-term inflation, therefore increasing short-term yields more than long-term yields (as described above and in the other answer). These reasons aren't set in stone, and just looking at graphs isn't a substitute for an actual analysis of the data, but logically, it seems plausible that the positive shock to oil prices, increases in the effective federal funds rate, and increases in inflation and expectations of inflation contributed at least partially to the inversion of the yield curve. Keep in mind that these factors are all interconnected as well, so the situation is certainly more complex. If you approve of this answer, be sure to vote up the other answer about the yield curve too.", "title": "" }, { "docid": "531551", "text": "\"These rates are so low because the cost of money is so low. Specifically, two rates are near zero. The Federal Reserve discount rate, which is \"\"the interest rate charged to commercial banks and other depository institutions on loans they receive from their regional Federal Reserve Bank's lending facility--the discount window.\"\" The effective federal funds rate, which is the rate banks pay when they trade balances with each other through the Federal Reserve. Banks want to profit on the loans they make, like mortgage loans. To do so, they try to maximize the difference between the rates they charge on mortgages and other loans (revenue), and the rates they pay savings account holders, the Federal Reserve or other banks to obtain funds (expenses). This means that the rates they offer to pay are as close to these rates as possible. As the charts shows, both rates have been cut significantly since the start of the recession, either through open market operations (the federal funds rate) or directly (the discount rate). The discount rate is set directly by the regional Federal Reserve banks every 14 days. In most cases, the federal funds rate is lower than the discount rate, in order to encourage banks to lend money to each other instead of borrowing it from the Fed. In the past, however, there have been rare instances where the federal funds rate has exceeded the discount rate, and it's been cheaper for banks to borrow money directly from the Fed than from each other.\"", "title": "" }, { "docid": "571181", "text": "\"How should I allocate short-term assets in a rising-interest rate environment? Assuming that the last part is correct, there could be bear bond funds that short bonds that could work well as a way to invest. However, bear in that the the \"\"rising-interest rate environment\"\" is part of the basis that may or may not be true in the end as I'm not sure I've seen anything to tell me why rates couldn't stay where they are for another couple of years or more. Long-Term Capital Management would be a cautionary tale before about bonds that had assumptions that backfired when something that wasn't supposed to happen, happened. Thus, while you can say there is \"\"rising-interest rate environment\"\" what else are you prepared to assume and how certain are you of that happening? An alternate theory here would be that \"\"junk bonds\"\" may do well because the economy has to be heating up for rates to rise and thus the bonds that are priced down so much because of default risk may turn out to not go bust and thus could do well. Course this would carry the \"\"Your mileage may vary\"\" and without a working time machine I couldn't say which funds will be good and which would suck. As for what I would do if I was dealing with my own money: Money market funds and CDs would likely be my suggestion for the short-term where I want to prevent principal risk. This is likely what I would do if I believed the rising rate environment is here.\"", "title": "" }, { "docid": "353662", "text": "\"Scenario 1 is typically the better description. If commercial banks were allowed to simply \"\"create\"\" money, they wouldn't be in the mess they're in now. In the U.S., the central bank is the Federal Reserve or Fed, and is the only entity (not the government, not the banks, not the people) that is allowed to create money \"\"out of thin air\"\". It does this primarily by buying government debt. The government spends more than it takes in, and so to come up with the deficit, it issues bonds. The Fed buys a certain amount of these bonds, and simply prints the money (or more realistically authorized the electronic transfer of $X to the Treasury) which the government then spends. That places money in the hands of corporations and the people, who turn around and spend it. However, long-term, the interest charges on money borrowed from the Fed will actually remove money from the economy. The central banks, therefore, have to constantly make marginal changes to various monetary policy tools they have when the economy is just humming along. If they do nothing, then too much of a short-term increase in money supply will result in there being \"\"too much money\"\" which makes an individual monetary unit worth less (inflation), while making money too hard to get will reduce the rate at which it's spent, reducing GDP and causing recessions. The exact scenario you describe is typically seen in cases where the government is running with a balanced budget, and the central bank thus can't give its \"\"new money\"\" to the government to spend when it wants to increase the money supply. In that situation, the central bank instead lowers its lending rate, the percentage interest that it will charge on loans made to other banks, thereby encouraging those banks to borrow more of the money created by the central bank. Those banks will then use the money to make loans, invest in the market, etc etc which puts the money in the economy. In the U.S., the Fed does have this tool as well, but increases or decreases in the \"\"Federal Funds Rate\"\" are typically used to influence the rate that banks charge each other to borrow money, thus encouraging or discouraging this lending. A lowering in the interest rate makes banks more likely to borrow from each other (and from the Fed but the amount of money \"\"created\"\" this way is a drop in the bucket compared to current \"\"quantitative easing\"\"), and thus increases the \"\"turnover\"\" of the existing money in the economy (how many times a theoretical individual dollar is spent in a given time period).\"", "title": "" }, { "docid": "134109", "text": "\"401(k) doesn't have a \"\"return rate\"\", because 401(k) is not a type of investment -- it is a vehicle for investment, with certain tax treatments. Just like your money that's not in a 401(k), you can invest it in either the bank, a CD, stocks, mutual funds, bonds, etc., you can similarly (depending on the options given to you by your 401(k) plan) invest the money in the 401(k) in a cash account, buy stocks, mutual funds, etc. Your return is dependent on how you invest your money, not whether it's in a 401(k) or not. Whether it's in a (Roth or Traditional) 401(k) simply affects when and how it gets taxed. (It is true that most 401(k) plans offer little variety in types of investments you can choose; however, this is not a big deal, as chances are that in a few years, you will leave your company, at which point you are able to rollover the 401(k) into an IRA, at which point you will have many, many options for how to invest it.) To make a valid comparison, you should be comparing the same type of investment in both cases. That means, you should assume the same return for both the money outside the 401(k), and the money inside the 401(k), and only consider the taxes and penalties (if you plan to withdraw early).\"", "title": "" } ]
81	Acute ablation of Snail in the embryonic cortex affects the proliferation and number of embryonic cortical precursors.	[ { "docid": "1797622", "text": "Asymmetric cell division and apoptosis (programmed cell death) are two fundamental processes that are important for the development and function of multicellular organisms. We have found that the processes of asymmetric cell division and apoptosis can be functionally linked. Specifically, we show that asymmetric cell division in the nematode Caenorhabditis elegans is mediated by a pathway involving three genes, dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail, that directly control the enzymatic machinery responsible for apoptosis. Interestingly, the MIDA1-like protein GlsA of the alga Volvox carteri, as well as the Snail-related proteins Snail, Escargot, and Worniu of Drosophila melanogaster, have previously been implicated in asymmetric cell division. Therefore, C. elegans dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail may be components of a pathway involved in asymmetric cell division that is conserved throughout the plant and animal kingdoms. Furthermore, based on our results, we propose that this pathway directly controls the apoptotic fate in C. elegans, and possibly other animals as well.", "title": "Control of Apoptosis by Asymmetric Cell Division" } ]	[ { "docid": "38919140", "text": "The Snail transcription factor plays a key role in regulating diverse developmental processes but is not thought to play a role in mammalian neural precursors. Here, we have examined radial glial precursor cells of the embryonic murine cortex and demonstrate that Snail regulates their survival, self-renewal, and differentiation into intermediate progenitors and neurons via two distinct and separable target pathways. First, Snail promotes cell survival by antagonizing a p53-dependent death pathway because coincident p53 knockdown rescues survival deficits caused by Snail knockdown. Second, we show that the cell cycle phosphatase Cdc25b is regulated by Snail in radial precursors and that Cdc25b coexpression is sufficient to rescue the decreased radial precursor proliferation and differentiation observed upon Snail knockdown. Thus, Snail acts via p53 and Cdc25b to coordinately regulate multiple aspects of mammalian embryonic neural precursor biology.", "title": "Snail coordinately regulates downstream pathways to control multiple aspects of mammalian neural precursor development." }, { "docid": "16964262", "text": "Precursor cells of the embryonic cortex sequentially generate neurons and then glial cells, but the mechanisms regulating this neurogenic-to-gliogenic transition are unclear. Using cortical precursor cultures, which temporally mimic this in vivo differentiation pattern, we demonstrate that cortical neurons synthesize and secrete the neurotrophic cytokine cardiotrophin-1, which activates the gp130-JAK-STAT pathway and is essential for the timed genesis of astrocytes in vitro. Our data indicate that a similar phenomenon also occurs in vivo. In utero electroporation of neurotrophic cytokines in the environment of embryonic cortical precursors causes premature gliogenesis, while acute perturbation of gp130 in cortical precursors delays the normal timed appearance of astrocytes. Moreover, the neonatal cardiotrophin-1-/- cortex contains fewer astrocytes. Together, these results describe a neural feedback mechanism; newly born neurons produce cardiotrophin-1, which instructs multipotent cortical precursors to generate astrocytes, thereby ensuring that gliogenesis does not occur until neurogenesis is largely complete.", "title": "Evidence that Embryonic Neurons Regulate the Onset of Cortical Gliogenesis via Cardiotrophin-1" }, { "docid": "18038250", "text": "Within the developing mammalian CNS, growth factors direct multipotent precursors to generate neurons versus glia, a process that if perturbed might lead to neural dysfunction. In this regard, genetic mutations resulting in constitutive activation of the protein tyrosine phosphatase SHP-2 cause Noonan Syndrome (NS), which is associated with learning disabilities and mental retardation. Here, we demonstrate that genetic knockdown of SHP-2 in cultured cortical precursors or in the embryonic cortex inhibited basal neurogenesis and caused enhanced and precocious astrocyte formation. Conversely, expression of an NS SHP-2 mutant promoted neurogenesis and inhibited astrogenesis. Neural cell-fate decisions were similarly perturbed in a mouse knockin model that phenocopies human NS. Thus, SHP-2 instructs precursors to make neurons and not astrocytes during the neurogenic period, and perturbations in the relative ratios of these two cell types upon constitutive SHP-2 activation may contribute to the cognitive impairments in NS patients.", "title": "Control of CNS Cell-Fate Decisions by SHP-2 and Its Dysregulation in Noonan Syndrome" }, { "docid": "33796570", "text": "Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1 null mouse embryos by generating a conditional mutation in the NF1 gene using Cre/loxP technology. Introduction of a Synapsin I promoter driven Cre transgenic mouse strain into the conditional NF1 background has ablated NF1 function in most differentiated neuronal populations. These mice have abnormal development of the cerebral cortex, which suggests that NF1 has an indispensable role in this aspect of CNS development. Furthermore, although they are tumor free, these mice display extensive astrogliosis in the absence of conspicuous neurodegeneration or microgliosis. These results indicate that NF1-deficient neurons are capable of inducing reactive astrogliosis via a non-cell autonomous mechanism.", "title": "Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain." }, { "docid": "15833835", "text": "Adult neural stem/progenitor (B1) cells within the walls of the lateral ventricles generate different types of neurons for the olfactory bulb (OB). The location of B1 cells determines the types of OB neurons they generate. Here we show that the majority of mouse B1 cell precursors are produced between embryonic days (E) 13.5 and 15.5 and remain largely quiescent until they become reactivated postnatally. Using a retroviral library carrying over 100,000 genetic tags, we found that B1 cells share a common progenitor with embryonic cells of the cortex, striatum, and septum, but this lineage relationship is lost before E15.5. The regional specification of B1 cells is evident as early as E11.5 and is spatially linked to the production of neurons that populate different areas of the forebrain. This study reveals an early embryonic regional specification of postnatal neural stem cells and the lineage relationship between them and embryonic progenitor cells.", "title": "Embryonic Origin of Postnatal Neural Stem Cells" }, { "docid": "16939583", "text": "Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.", "title": "2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size." }, { "docid": "23901235", "text": "Neurogenesis occurs in the hippocampus of the developing and adult brain due to the presence of multipotent stem cells and restricted precursor cells at different stages of differentiation. It has been proposed that they may be of potential benefit for use in cell transplantation approaches for neurodegenerative disorders and trauma. Prolonged release of interleukin-1β (IL-1β) from activated microglia has a deleterious effect on hippocampal neurons and is implicated in the impaired neurogenesis and cognitive dysfunction associated with aging, Alzheimer's disease and depression. This study assessed the effect of IL-1β on the proliferation and differentiation of embryonic rat hippocampal NPCs in vitro. We show that IL-1R1 is expressed on proliferating NPCs and that IL-1β treatment decreases cell proliferation and neurosphere growth. When NPCs were differentiated in the presence of IL-1β, a significant reduction in the percentages of newly-born neurons and post-mitotic neurons and a significant increase in the percentage of astrocytes was observed in these cultures. These effects were attenuated by IL-1 receptor antagonist. These data reveal that IL-1β exerts an anti-proliferative, anti-neurogenic and pro-gliogenic effect on embryonic hippocampal NPCs, which is mediated by IL-1R1. The present results emphasise the consequences of an inflammatory environment during NPC development, and indicate that strategies to inhibit IL-1β signalling may be necessary to facilitate effective cell transplantation approaches or in conditions where endogenous hippocampal neurogenesis is impaired.", "title": "A role for interleukin-1β in determining the lineage fate of embryonic rat hippocampal neural precursor cells." }, { "docid": "16090672", "text": "Dynein at the cortex contributes to microtubule-based positioning processes such as spindle positioning during embryonic cell division and centrosome positioning during fibroblast migration. To investigate how cortical dynein interacts with microtubule ends to generate force and how this functional association impacts positioning, we have reconstituted the 'cortical' interaction between dynein and dynamic microtubule ends in an in vitro system using microfabricated barriers. We show that barrier-attached dynein captures microtubule ends, inhibits growth, and triggers microtubule catastrophes, thereby controlling microtubule length. The subsequent interaction with shrinking microtubule ends generates pulling forces up to several pN. By combining experiments in microchambers with a theoretical description of aster mechanics, we show that dynein-mediated pulling forces lead to the reliable centering of microtubule asters in simple confining geometries. Our results demonstrate the intrinsic ability of cortical microtubule-dynein interactions to regulate microtubule dynamics and drive positioning processes in living cells.", "title": "Cortical Dynein Controls Microtubule Dynamics to Generate Pulling Forces that Position Microtubule Asters" }, { "docid": "3095620", "text": "The homologues of the two distinct architectonic areas 44 and 45 that constitute the anterior language zone (Broca's region) in the human ventrolateral frontal lobe were recently established in the macaque monkey. Although we know that the inferior parietal lobule and the lateral temporal cortical region project to the ventrolateral frontal cortex, we do not know which of the several cortical areas found in those regions project to the homologues of Broca's region in the macaque monkey and by means of which white matter pathways. We have used the autoradiographic method, which permits the establishment of the cortical area from which axons originate (i.e., the site of injection), the precise course of the axons in the white matter, and their termination within particular cortical areas, to examine the parietal and temporal connections to area 44 and the two subdivisions of area 45 (i.e., areas 45A and 45B). The results demonstrated a ventral temporo-frontal stream of fibers that originate from various auditory, multisensory, and visual association cortical areas in the intermediate superolateral temporal region. These axons course via the extreme capsule and target most strongly area 45 with a more modest termination in area 44. By contrast, a dorsal stream of axons that originate from various cortical areas in the inferior parietal lobule and the adjacent caudal superior temporal sulcus was found to target both areas 44 and 45. These axons course in the superior longitudinal fasciculus, with some axons originating from the ventral inferior parietal lobule and the adjacent superior temporal sulcus arching and forming a simple arcuate fasciculus. The cortex of the most rostral part of the inferior parietal lobule is preferentially linked with the ventral premotor cortex (ventral area 6) that controls the orofacial musculature. The cortex of the intermediate part of the inferior parietal lobule is linked with both areas 44 and 45. These findings demonstrate the posterior parietal and temporal connections of the ventrolateral frontal areas, which, in the left hemisphere of the human brain, were adapted for various aspects of language production. These precursor circuits that are found in the nonlinguistic, nonhuman, primate brain also exist in the human brain. The possible reasons why these areas were adapted for language use in the human brain are discussed. The results throw new light on the prelinguistic precursor circuitry of Broca's region and help understand functional interactions between Broca's ventrolateral frontal region and posterior parietal and temporal association areas.", "title": "Distinct Parietal and Temporal Pathways to the Homologues of Broca's Area in the Monkey" }, { "docid": "2437807", "text": "The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube–like structures in the presence of fibroblast growth factor 2 (FGF-2). Neural precursors within these formations were isolated by selective enzymatic digestion and further purified on the basis of differential adhesion. Following withdrawal of FGF-2, they differentiated into neurons, astrocytes, and oligodendrocytes. After transplantation into the neonatal mouse brain, human ES cell–derived neural precursors were incorporated into a variety of brain regions, where they differentiated into both neurons and astrocytes. No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair.", "title": "In vitro differentiation of transplantable neural precursors from human embryonic stem cells" }, { "docid": "3090454", "text": "In 93 allograft recipients, the numbers of marrow B-cell precursors on days 80 and 365 correlated with the counts of circulating B cells, suggesting that the posttransplantation B-cell deficiency is at least in part due to insufficient B lymphopoiesis. Factors that could affect B lymphopoiesis were evaluated. The number of marrow B-cell precursors on days 30 and 80 was at least 4-fold lower in patients with grade 2 to 4 acute graft-versus-host disease (GVHD) compared with patients with grade 0 to 1 acute GVHD. The number of B-cell precursors on day 365 was 18-fold lower in patients with extensive chronic GVHD compared with patients with no or limited chronic GVHD. The number of B-cell precursors was not related to CD34 cell dose, type of transplant (marrow versus blood stem cells), donor age, or patient age. It was concluded that posttransplantation B-cell deficiency results in part from inhibition of B lymphopoiesis by GVHD and/or its treatment.", "title": "Factors influencing B lymphopoiesis after allogeneic hematopoietic cell transplantation." }, { "docid": "4457834", "text": "The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.", "title": "Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells" }, { "docid": "12903921", "text": "It has been proved that oxidative stress increases when leukemia is accompanied by depression. This fact may indicate the role of oxidative stress in the development of depression in cancer patients. The aim of this study was to determine whether the acute myeloid leukemia of Brown Norway rats, which is accompanied by oxidative stress, evoked behavioral and receptor changes resembling alterations characteristic of rat models of depression. The rats were divided into two groups: leukemic rats and healthy control. Leukemia was induced through intraperitoneal injection of 10(7) promyelocytic leukemia cells to the Brown Norway rats. Depression-like behavior was evaluated in the forced swim test at 30 or 34 days after leukemic cells injection. The rats were killed after the evaluation and the spleen, brain cortex and hippocampus were excised. The red-ox state was assessed in homogenates of tissues by measuring total glutathione (GSH) content, the ferric ion reducing ability of plasma (FRAP) level, expression of heme oxygenase-1 (HO-1), biliverdin reductase (BvR) and ferritin mRNA, superoxide dismutase (SOD) activity, as well as malondialdehyde (MDA) concentration. Radioligand binding assay was used to assess of the effect of leukemia on cortical receptors. Leukemic cells were identified using RM-124 antibody by FACS Calibur flow cytometry. Leukemia influenced locomotory activity as well as forced swim test behavior in a 34-day series of experiments. Signs of oxidative stress in leukemic rats were observed in each examined stage of leukemia development. The FRAP values and glutathione contents, were significantly lowered whereas HO-1 mRNA expression, and malonodialdehyde concentrations were significantly increased in the spleen and brain structures of leukemic rats in comparison with the healthy controls. A significant increase in the potency of glycine to displace [(3)H]L-689,560 from the strychnine-insensitive glycine site of the N-methyl-D-aspartic (NMDA) receptors receptor complex in cortical homogenates of the leukemic rats in 30- and 34-day experimental series was observed in comparison with the control. Upregulation of 5-HT(2A) receptors was observed in rat cortex after 30 days of leukemia development but not in 34-days series compared with the control. It is concluded that disturbances in antioxidant system in brain cortex were accompanied by an activation of glycine sites of the NMDA receptor complex, regardless of stage of leukemia development, which are characteristic of model of depression. Findings of our study demonstrate the link between glutamatergic activity, oxidative stress and leukemia.", "title": "Evaluation of oxidative status and depression-like responses in Brown Norway rats with acute myeloid leukemia" }, { "docid": "17119869", "text": "The pancreas emerges independently from dorsal and ventral domains of embryonic gut endoderm. Gene inactivation experiments in mice have identified factors required for dorsal pancreas development, but factors that initiate the ventral pancreas have remained elusive. In this study, we investigated the hypothesis that the emergence of the ventral pancreas is related to the emergence of the liver. We find that the liver and ventral pancreas are specified at the same time and in the same general domain of cells. Using embryo tissue explantation experiments, we find that the default fate of the ventral foregut endoderm is to activate the pancreas gene program. FGF signalling from the cardiac mesoderm diverts this endoderm to express genes for liver instead of those for pancreas. No evidence was found to indicate that the cell type choice for pancreas or liver involves a selection for growth or viability. Cardiac mesoderm or FGF induces the local expression of sonic hedgehog, which in turn is inhibitory to pancreas but not to liver. The bipotential precursor cell population for pancreas and liver in embryonic development and its fate selection by FGF has features that appear to be recapitulated in the adult pancreas and are reflected in the evolution of these organs.", "title": "A bipotential precursor population for pancreas and liver within the embryonic endoderm." }, { "docid": "5002665", "text": "The embryonic cell lineage of Caenorhabditis elegans has been traced from zygote to newly hatched larva, with the result that the entire cell lineage of this organism is now known. During embryogenesis 671 cells are generated; in the hermaphrodite 113 of these (in the male 111) undergo programmed death and the remainder either differentiate terminally or become postembryonic blast cells. The embryonic lineage is highly invariant, as are the fates of the cells to which it gives rise. In spite of the fixed relationship between cell ancestry and cell fate, the correlation between them lacks much obvious pattern. Thus, although most neurons arise from the embryonic ectoderm, some are produced by the mesoderm and a few are sisters to muscles; again, lineal boundaries do not necessarily coincide with functional boundaries. Nevertheless, cell ablation experiments (as well as previous cell isolation experiments) demonstrate substantial cell autonomy in at least some sections of embryogenesis. We conclude that the cell lineage itself, complex as it is, plays an important role in determining cell fate. We discuss the origin of the repeat units (partial segments) in the body wall, the generation of the various orders of symmetry, the analysis of the lineage in terms of sublineages, and evolutionary implications.", "title": "The embryonic cell lineage of the nematode Caenorhabditis elegans." }, { "docid": "40254495", "text": "Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that \"temporal synexpression\" predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.", "title": "Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development." }, { "docid": "4412772", "text": "Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase, as well as Cdk1 to proceed through mitosis. This model has been challenged by recent genetic evidence that mice survive in the absence of individual interphase Cdks. Moreover, most mouse cell types proliferate in the absence of two or even three interphase Cdks. Similar results have been obtained on ablation of some of the activating subunits of Cdks, such as the D-type and E-type cyclins. Here we show that mouse embryos lacking all interphase Cdks (Cdk2, Cdk3, Cdk4 and Cdk6) undergo organogenesis and develop to midgestation. In these embryos, Cdk1 binds to all cyclins, resulting in the phosphorylation of the retinoblastoma protein pRb and the expression of genes that are regulated by E2F transcription factors. Mouse embryonic fibroblasts derived from these embryos proliferate in vitro, albeit with an extended cell cycle due to inefficient inactivation of Rb proteins. However, they become immortal on continuous passage. We also report that embryos fail to develop to the morula and blastocyst stages in the absence of Cdk1. These results indicate that Cdk1 is the only essential cell cycle Cdk. Moreover, they show that in the absence of interphase Cdks, Cdk1 can execute all the events that are required to drive cell division.", "title": "Cdk1 is sufficient to drive the mammalian cell cycle" }, { "docid": "19204979", "text": "Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP+ cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient–X-linked, mouse muscular dystrophy (scid–mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.", "title": "Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells" }, { "docid": "26612216", "text": "ATP-dependent chromatin remodeling complexes are a notable group of epigenetic modifiers that use the energy of ATP hydrolysis to change the structure of chromatin, thereby altering its accessibility to nuclear factors. BAF250a (ARID1a) is a unique and defining subunit of the BAF chromatin remodeling complex with the potential to facilitate chromosome alterations critical during development. Our studies show that ablation of BAF250a in early mouse embryos results in developmental arrest (about embryonic day 6.5) and absence of the mesodermal layer, indicating its critical role in early germ-layer formation. Moreover, BAF250a deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells under normal feeder-free culture conditions. Interestingly, this phenotype can be partially rescued by the presence of embryonic fibroblast cells. DNA microarray, immunostaining, and RNA analyses revealed that BAF250a-mediated chromatin remodeling contributes to the proper expression of numerous genes involved in ES cell self-renewal, including Sox2, Utf1, and Oct4. Furthermore, the pluripotency defects in BAF250a mutant ES cells appear to be cell lineage-specific. For example, embryoid body-based analyses demonstrated that BAF250a-ablated stem cells are defective in differentiating into fully functional mesoderm-derived cardiomyocytes and adipocytes but are capable of differentiating into ectoderm-derived neurons. Our results suggest that BAF250a is a key component of the gene regulatory machinery in ES cells controlling self-renewal, differentiation, and cell lineage decisions.", "title": "ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a." }, { "docid": "24523573", "text": "Previous studies have shown that synchronized beta frequency (14-30 Hz) oscillations in the primary motor cortex are involved in maintaining steady contractions of contralateral arm and hand muscles. However, little is known about the role of postcentral cortical areas in motor maintenance and their patterns of interaction with motor cortex. We investigated the functional relations of beta-synchronized neuronal assemblies in pre- and postcentral areas of two monkeys as they pressed a hand lever during the wait period of a visual discrimination task. By using power and coherence spectral analysis, we identified a beta-synchronized large-scale network linking pre- and postcentral areas. We then used Granger causality spectra to measure directional influences among recording sites. In both monkeys, strong Granger causal influences were observed from primary somatosensory cortex to both motor cortex and inferior posterior parietal cortex, with the latter area also exerting Granger causal influences on motor cortex. Granger causal influences from motor cortex to postcentral sites, however, were weak in one monkey and not observed in the other. These results are the first, to our knowledge, to demonstrate in awake monkeys that synchronized beta oscillations bind multiple sensorimotor areas into a large-scale network during motor maintenance behavior and carry Granger causal influences from primary somatosensory and inferior posterior parietal cortices to motor cortex.", "title": "Beta oscillations in a large-scale sensorimotor cortical network: directional influences revealed by Granger causality." }, { "docid": "12887068", "text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. The role of the H3.3K27M mutation in tumorigenesis is not fully understood. Here, we use a human embryonic stem cell system to model this tumor. We show that H3.3K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genome-wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin as an inhibitor of tumor cell growth in vitro and in mice.", "title": "Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation" }, { "docid": "13878124", "text": "Radial glial cells (RGCs) in the developing cerebral cortex are progenitors for neurons and glia, and their processes serve as guideposts for migrating neurons. So far, it has remained unclear whether RGC processes also control the function of RGCs more directly. Here, we show that RGC numbers and cortical size are reduced in mice lacking beta1 integrins in RGCs. TUNEL stainings and time-lapse video recordings demonstrate that beta1-deficient RGCs processes detach from the meningeal basement membrane (BM) followed by apoptotic death of RGCs. Apoptosis is also induced by surgical removal of the meninges. Finally, mice lacking the BM components laminin alpha2 and alpha4 show defects in the attachment of RGC processes at the meninges, a reduction in cortical size, and enhanced apoptosis of RGC cells. Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size.", "title": "Regulation of radial glial survival by signals from the meninges." }, { "docid": "10846815", "text": "The actin cortex both facilitates and hinders the exocytosis of secretory granules. How cells consolidate these two opposing roles was not well understood. Here we show that antigen activation of mast cells induces oscillations in Ca(2+) and PtdIns(4,5)P(2) lipid levels that in turn drive cyclic recruitment of N-WASP and cortical actin level oscillations. Experimental and computational analysis argues that vesicle fusion correlates with the observed actin and Ca(2+) level oscillations. A vesicle secretion cycle starts with the capture of vesicles by actin when cortical F-actin levels are high, followed by vesicle passage through the cortex when F-actin levels are low, and vesicle fusion with the plasma membrane when Ca(2+) levels subsequently increase. Thus, cells employ oscillating levels of Ca(2+), PtdIns(4,5)P(2) and cortical F-actin to increase secretion efficiency, explaining how the actin cortex can function as a carrier as well as barrier for vesicle secretion.", "title": "Coordinated oscillations in cortical actin and Ca2+ correlate with cycles of vesicle secretion" }, { "docid": "36651210", "text": "Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.", "title": "Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst." }, { "docid": "4335423", "text": "Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown. Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial–haematopoietic precursors or haemogenic endothelial cells remains controversial. Proximity of endothelial and blood cells at sites of embryonic haematopoiesis, as well as their similar gene expression, led to the hypothesis of the endothelium generating blood. However, owing to lacking technology it has been impossible to observe blood cell emergence continuously at the single-cell level, and the postulated existence of haemogenic endothelial cells remains disputed. Here, using new imaging and cell-tracking methods, we show that embryonic endothelial cells can be haemogenic. By continuous long-term single-cell observation of mouse mesodermal cells generating endothelial cell and blood colonies, it was possible to detect haemogenic endothelial cells giving rise to blood cells. Living endothelial and haematopoietic cells were identified by simultaneous detection of morphology and multiple molecular and functional markers. Detachment of nascent blood cells from endothelium is not directly linked to asymmetric cell division, and haemogenic endothelial cells are specified from cells already expressing endothelial markers. These results improve our understanding of the developmental origin of mammalian blood and the potential generation of haematopoietic stem cells from embryonic stem cells.", "title": "Continuous single-cell imaging of blood generation from haemogenic endothelium" }, { "docid": "4311206", "text": "Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.", "title": "Conversion of Adult Pancreatic α-cells to β-cells After Extreme β-cell Loss" }, { "docid": "92499", "text": "Hematopoietic stem cells (HSCs) develop during embryogenesis in a complex process that involves multiple anatomical sites. Once HSC precursors have been specified from mesoderm, they have to mature into functional HSCs and undergo self-renewing divisions to generate a pool of HSCs. During this process, developing HSCs migrate through various embryonic niches, which provide signals for their establishment and the conservation of their self-renewal ability. These processes have to be recapitulated to generate HSCs from embryonic stem cells. Elucidating the interactions between developing HSCs and their niches should facilitate the generation and expansion of HSCs in vitro to exploit their clinical potential.", "title": "The journey of developing hematopoietic stem cells." }, { "docid": "14460402", "text": "The molecular mechanisms that regulate adult neural precursor cell (NPC) survival, and thus maintain adult neurogenesis, are not well defined. Here, we investigate the role of p63, a p53 family member, in adult NPC function in mice. Conditional ablation of p63 in adult NPCs or p63 haploinsufficiency led to reduced numbers of NPCs and newborn neurons in the neurogenic zones of the hippocampus and lateral ventricles and in the olfactory bulb. These reductions were attributable to enhanced apoptosis of NPCs and newborn neurons and were rescued by inhibition of caspase activity, p53, or the p53 apoptotic effector PUMA (p53-upregulated modulator of apoptosis). Moreover, these cellular deficits were functionally important because they led to perturbations in hippocampus-dependent memory formation. These results indicate that p63 regulates the numbers of adult NPCs and adult-born neurons as well as neural stem cell-dependent cognitive functions, and that it does so, at least in part, by inhibiting p53-dependent cell death.", "title": "p63 Regulates adult neural precursor and newly born neuron survival to control hippocampal-dependent Behavior." }, { "docid": "19770974", "text": "Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.", "title": "Prev \| Table of Contents Reports Embryonic Stem Cell Lines Derived from Human" }, { "docid": "19522248", "text": "We targeted the locus encoding the cyclin-dependent kinase 2 (CDK2) by homologous recombination in mouse embryonic stem (ES) cells. Embryonic fibroblasts lacking CDK2 proliferate normally and become immortal after continuous passage in culture. Elimination of a conditional Cdk2 allele in immortal cells does not have a significant effect on proliferation. Cdk2−/− mice are viable and survive for up to two years, indicating that CDK2 is also dispensable for proliferation and survival of most cell types. But CDK2 is essential for completion of prophase I during meiotic cell division in male and female germ cells, an unforeseen role for this cell cycle kinase.", "title": "Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice" } ]
5876	Investment in mutual fund in India for long term goals	[ { "docid": "281865", "text": "On reading couple of articles & some research over internet, I got to know about diversified investment where one should invest 70% in equity related & rest 30% in debt related funds Yes that is about right. Although the recommendation keeps varying a bit. However your first investment should not aim for diversification. Putting small amounts in multiple mutual funds may create paper work and tracking issues. My suggestion would be to start with an Index EFT or Large cap. Then move to balanced funds and mid caps etc. On this site we don't advise on specific funds. You can refer to moneycontrol.com or economictimes or quite a few other personal finance advisory sites to understand the top funds in the segments and decide on funds accordingly. PS: Rather than buying paper, buy it electronic, better you can now buy it as Demat. If you already have an Demat account it would be best to buy through it.", "title": "" }, { "docid": "183497", "text": "Buy only 'Direct' Plans, not regular. - Demat providers won't sell Direct plans, that you can do it through https://www.mfuindia.com Make sure expense ratio < 2.5% (With direct plans it will be much lesser) I hope these points will help you to take a better decision.", "title": "" } ]	[ { "docid": "386173", "text": "It isn't just ETFs, you have normal mutual funds in India which invest internationally. This could be convenient if you don't already have a depository account and a stockbroker. Here's a list of such funds, along with some performance data: Value Research - Equity: International: Long-term Performance. However, you should also be aware that in India, domestic equity and equity fund investing is tax-free in the long-term (longer than one year), but this exemption doesn't apply to international investments. Ref: Invest Around the World.", "title": "" }, { "docid": "88575", "text": "\"A mutual fund's return or yield has nothing to do with what you receive from the mutual fund. The annual percentage return is simply the percentage increase (or decrease!) of the value of one share of the mutual fund from January 1 till December 31. The cash value of any distributions (dividend income, short-term capital gains, long-term capital gains) might be reported separately or might be included in the annual return. What you receive from the mutual fund is the distributions which you have the option of taking in cash (and spending on whatever you like, or investing elsewhere) or of re-investing into the fund without ever actually touching the money. Regardless of whether you take a distribution as cash or re-invest it in the mutual fund, that amount is taxable income in most jurisdictions. In the US, long-term capital gains are taxed at different (lower) rates than ordinary income, and I believe that long-term capital gains from mutual funds are not taxed at all in India. You are not taxed on the increase in the value of your investment caused by an increase in the share price over the year nor do you get deduct the \"\"loss\"\" if the share price declined over the year. It is only when you sell the mutual fund shares (back to the mutual fund company) that you have to pay taxes on the capital gains (if you sold for a higher price) or deduct the capital loss (if you sold for a lower price) than the purchase price of the shares. Be aware that different shares in the sale might have different purchase prices because they were bought at different times, and thus have different gains and losses. So, how do you calculate your personal return from the mutual fund investment? If you have a money management program or a spreadsheet program, it can calculate your return for you. If you have online access to your mutual fund account on its website, it will most likely have a tool called something like \"\"Personal rate of return\"\" and this will provide you with the same calculations without your having to type in all the data by hand. Finally, If you want to do it personally by hand, I am sure that someone will soon post an answer writing out the gory details.\"", "title": "" }, { "docid": "393009", "text": "Waiting for the next economic downturn probably isn't the best plan at this point. While it could happen tomorrow, you may end up waiting a long time. If you would prefer not to think much about your investment and just let them grow then mutual funds are a really good option. Make sure you research them before you buy into any and make sure to diversify, as in buy into a lot of different mutual funds that cover different parts of the market. If you want to be more active in investing then start researching the market and stick to industries you have very good understanding of. It's tough to invest in a market you know nothing about. I'd suggest putting at least some of that into a retirement savings account for long term growth. Make sure you look at both your short term and long term goals. Letting an investment mature from age 20 through to retirement will net you plenty of compound interest but don't forget about your short term goals like possible cars, houses and families. Do as much research as you can and you will be fine!", "title": "" }, { "docid": "135596", "text": "This might be better suited to r/personalfinance but if you're looking to invest I'd say start with an index fund. The MER's (fees) for most other mutual funds take too heavy a chunk of returns to be worth it in a market where actively managed funds are either underperforming of performing at par with passive funds. Additionally if these are your first investments, make sure you're doing it with investment goals in mind. Is this money you're saving for short, medium, or long term? For medium and long term investing make sure you're doing it through a tax efficient instrument like an IRA or 401k.", "title": "" }, { "docid": "315741", "text": "It's not so much pros and cons as much as it is what are your savings goals? While it's best to start early to save money for retirement, you may have numerous short- to medium-term savings goals (school, down payment, etc). Here's a template you can consider. I would suggest that you open up an RRSP mutual fund or brokerage account and invest a certain amount that you feel free locking up for the next few decades and investing it in some sort of growth product (perhaps look at portfolios using the Couch Potato strategy). Then, also open up a TFSA mutual fund or brokerage account and use it to invest for medium-term goals (i.e. 5-10 years). Invest in products that will allow for some growth but with low chance of losing principle in that time frame. What I wouldn't do is open up a TFSA savings account and use it for day-to-day savings. The tax you save is negligible and you would need to keep track of deposits and withdrawals to ensure that you don't overcontribute for the tax year. Similarly, an RRSP savings account or GIC is far too conservative at your age, IMHO. Think of RRSP and TFSA as investment vehicles rather than accounts per se. Either type allows for you to invest in a vast array of products, including mutual funds, equities, some derivatives, gold, bonds, GICs, etc. To conclude, my view is to use RRSP to invest for conventional retirement goals, and use the TFSA to invest for medium-term and early retirement goals.", "title": "" }, { "docid": "240351", "text": "Just to clarify Short Team Goals & Long Term Goals... Long Term goals are for something in future, your retirement fund, Children’s education etc. Short Term goals are something in the near future, your down payment for car, house, and holiday being planned. First have both the long and short terms goals defined. Of Couse you would need to review both these goals on a ongoing basis... To meet the short term goals you would need to make short term investments. Having arrived at a short term goal value, you would now need to make a decision as to how much risk you are willing [also how much is required to take] to take in order to meet your goal. For example if you goal is to save Rs 100,000 by yearend for the car, and you can easily set aside Rs 8,000 every month, you don't really need to take a risk. A simple Term / Fixed Deposit would suffice you to meet your goal. On the other hand if you can only save Rs 6,000 a year, then you would need to invest this into something that would return you around 35%. You would now need to take a risk. Stocks market is one option, there are multiple types of trades [day trades, shorts, options, regular trades] that one can do ... however the risk can wipe out even your capital. As you don't know these types of investments, suggest you start with dummy investing using quite a few free websites, MoneyControl is one such site, you get pseudo money and can buy sell and see how things actually move. This should teach you something about making quick gains or losses without actually gaining or loosing real money. Once you reach some confidence level, you can start trading using real money by opening a trading account almost every other bank in India offers online trading linked to bank account. Never lose sight of risk appetite, and revise if every now and then. When you don't have dependents, you can easily risk money for potential bumper, however after you have other commitments, you may want to tone down... Edit: http://moneybhai.moneycontrol.com/moneybhai-rules.html is one such site, there are quite a few others as well that offer you to trade on virtual money. Try this for few months and you will understand whether you are making right decissions or not.", "title": "" }, { "docid": "385600", "text": "For some ideas on investing priority guidelines, see Oversimplify it for me: the correct order of investing. Congratulations on being debt free! My advice to you is to do what you can to remain debt free. You could certainly invest the money; it will earn much more over the long-term in a stock mutual fund than it would left in a savings account. However, if you need any of this money in the next few years, it would be a shame if it lost money in the short-term. How much do you need to finish grad school? Don't invest that money in the stock market, because you will need it over the next few years. Likewise, think about other expenses that are coming up. Will your car need to be replaced in the next couple of years? Will you have enough income to meet your living expenses while you are in grad school, or will you need some of this to money to help with that? Finally, it would be good to keep some extra as an emergency fund, so you can easily pay for any unexpected expenses that come up. If you can make it through grad school debt free, you will be much better off than if you invest all the money but take out student loans in the process. After you've accounted for all of that, whatever is left of the money could definitely be invested. If your goal is to start a retirement fund, an index mutual fund invested inside a Roth IRA is a great place to start.", "title": "" }, { "docid": "594257", "text": "\"My original plan was to wait for the next economic downturn and invest in index funds. These funds have historically yielded 6-7% annually when entered at any given time, but maybe around 8-9% annually when entered during a recession. These numbers have been adjusted for inflation. Questions or comments on this strategy? Educate yourself as index funds are merely a strategy that could be applied to various asset classes such as US Large-cap value stocks, Emerging Market stocks, Real Estate Investment Trusts, US Health Care stocks, Short-term bonds, and many other possibilities. Could you be more specific about which funds you meant as there is some great work by Fama and French on the returns of various asset classes over time. What about a Roth IRA? Mutual fund? Roth IRA is a type of account and not an investment in itself, so while I think it is a good idea to have Roth IRA, I would highly advise researching the ins and outs of this before assuming you can invest in one. You do realize that index funds are just a special type of mutual fund, right? It is also worth noting that there are a few kinds of mutual funds: Open-end, exchange-traded and closed-end. Which kind did you mean? What should I do with my money until the market hits another recession? Economies have recessions, markets have ups and downs. I'd highly consider forming a real strategy rather than think, \"\"Oh let's toss it into an index fund until I need the money,\"\" as that seems like a recipe for disaster. Figure out what long-term financial goals do you have in mind, how OK are you with risk as if the market goes down for more than a few years straight, are you OK with seeing those savings be cut in half or worse?\"", "title": "" }, { "docid": "518487", "text": "One estimate is to sell today, estimate the taxes, and determine how much cash you need to set aside over the next 12 months. The is no way to calculate what impact dividends and capital gains the funds will have, because unlike interest they aren't guaranteed. The other complexity is that the funds themselves could drop in value. In that case the dividends and capital gains may not even be enough to get you back to even. I use mutual funds to invest over the long term, with the idea of spending the funds over decades. When needing to save for a short term goal, I use banking products. They are guaranteed not to lose value, and the interest changes are slowerand thus easier to predict.", "title": "" }, { "docid": "473647", "text": "Other answers are already very good, but I'd like to add one step before taking the advice of the other answers... If you still can, switch to a 15 year mortgage, and figure out what percentage of your take-home pay the new payment is. This is the position taken by Dave Ramsey, and I believe this will give you a better base from which to launch your other goals for two reasons: Since you are then paying it off faster at a base payment, you may then want to take MrChrister's advice but put all extra income toward investments, feeling secure that your house will be paid off much sooner anyway (and at a lower interest rate). Dave's advice isn't for everyone, because he takes a very long-term view. However, in the long-term, it is great advice. See here for more. JoeTaxpayer is right, you will not see anything near guaranteed yearly rates in mutual funds, so make sure they are part of a long-term investing plan. You are not investing your time in learning the short-term stock game, so stay away from it. As long as you are continuing to learn in your own career, you should see very good short-term gains there anyway.", "title": "" }, { "docid": "87722", "text": "In my opinion, if you are doing long-term investing, this is a non-issue. The difference of hours in being able to trade an ETF during the day vs. only being able to trade a traditional mutual fund at day-end is irrelevant if you are holding the investment for a long time. If you are engaging in day trading, market timing, or other advanced/controversial trading practices, then I suppose it could make a difference. For the way I invest (index funds, long-term, set-it-and-forget-it), ETFs have no advantage over traditional mutual funds.", "title": "" }, { "docid": "333004", "text": "First of all kudos to you for seeing the value in saving at a young age. There are several different things you can mean by this and I'm not sure which is accurate so I am going to address the first two that I thought of. If you are selling your investments because you need the money (emergency expenses, saved enough for a short term goal, whatever the reason) then this may not be the best solution for your savings. Investing in mutual funds, ETFs, stocks, 401k, IRA, etc are typically for longer term goals such as a goal that is 10+ years away (maybe buying a home, paying for college for your children, retirement, etc). If you are selling your investments because you believe that another investment is performing better and you want to get in on that one instead what I would suggest is leaving the money you have invested where it is and starting future investments in the new fund/ETF you are interested in. For example if you have $2000 invested in fund X and now you do some research and fund Q looks more appealing that is great, start investing in fund Q with your next deposit. Any research you do will be based on past results, there is nothing that guarantees that fund Q will continue doing better than the fund X you already have. Trying to time the market rarely ends well for the investor. I would encourage you to continue saving money a bit at a time just like you have been doing. Avoid selling your investments until it is time to sell them for whatever goal you intended them for. Set aside some cash to cover any unexpected expenses so you won't have to sell your investments to cover the costs, even at 18 unplanned things happen.", "title": "" }, { "docid": "45190", "text": "\"A mutual fund could make two different kinds of distributions to you: Capital gains: When the fund liquidates positions that it holds, it may realize a gain if it sells the assets for a greater price than the fund purchased them for. As an example, for an index fund, assets may get liquidated if the underlying index changes in composition, thus requiring the manager to sell some stocks and purchase others. Mutual funds are required to distribute most of their income that they generate in this way back to its shareholders; many often do this near the end of the calendar year. When you receive the distribution, the gains will be categorized as either short-term (the asset was held for less than one year) or long-term (vice versa). Based upon the holding period, the gain is taxed differently. Currently in the United States, long-term capital gains are only taxed at 15%, regardless of your income tax bracket (you only pay the capital gains tax, not the income tax). Short-term capital gains are treated as ordinary income, so you will pay your (probably higher) tax rate on any cash that you are given by your mutual fund. You may also be subject to capital gains taxes when you decide to sell your holdings in the fund. Any profit that you made based on the difference between your purchase and sale price is treated as a capital gain. Based upon the period of time that you held the mutual fund shares, it is categorized as a short- or long-term gain and is taxed accordingly in the tax year that you sell the shares. Dividends: Many companies pay dividends to their stockholders as a way of returning a portion of their profits to their collective owners. When you invest in a mutual fund that owns dividend-paying stocks, the fund is the \"\"owner\"\" that receives the dividend payments. As with capital gains, mutual funds will redistribute these dividends to you periodically, often quarterly or annually. The main difference with dividends is that they are always taxed as ordinary income, no matter how long you (or the fund) have held the asset. I'm not aware of Texas state tax laws, so I can't comment on your other question.\"", "title": "" }, { "docid": "94040", "text": "Short-term to intermediate-term corporate bond funds are available. The bond fund vehicle helps manage the credit risk, while the short terms help manage inflation and interest rate risk. Corporate bond funds will have fewer Treasuries bonds than a general-purpose short-term bond fund: it sounds like you're interested in things further out along the risk curve than a 0.48% return on a 5-year bond, and thus don't care for the Treasuries. Corporate bonds are generally safer than stocks because, in bankruptcy, all your bondholders have to be paid in full before any equity-holders get a penny. Stocks are much more volatile, since they're essentially worth the value of their profits after paying all their debt, taxes, and other expenses. As far as stocks are concerned, they're not very good for the short term at all. One of the stabler stock funds would be something like the Vanguard Equity Income Fund, and it cautions: This fund is designed to provide investors with an above-average level of current income while offering exposure to the stock market. Since the fund typically invests in companies that are dedicated to consistently paying dividends, it may have a higher yield than other Vanguard stock mutual funds. The fund’s emphasis on slower-growing, higher-yielding companies can also mean that its total return may not be as strong in a significant bull market. This income-focused fund may be appropriate for investors who have a long-term investment goal and a tolerance for stock market volatility. Even the large-cap stable companies can have their value fall dramatically in the short term. Look at its price chart; 2008 was brutal. Avoid stocks if you need to spend your money within a couple of years. Whatever you choose, read the prospectus to understand the risks.", "title": "" }, { "docid": "500486", "text": "First, it's not always the case that ETFs have lower expenses than the equivalent mutual funds. For example, in the Vanguard family of funds the expense ratio for the ETF version is the same as it is for the Admiral share class in the mutual fund version. With that in mind, the main advantages of a mutual fund over an equivalent ETF are: From a long-term investor's point of view, the main disadvantage of mutual funds relative to ETFs is the minimum account sizes. Especially if the fund has multiple share classes (i.e., where better classes get lower expense ratios), you might have to have quite a lot of money invested in the fund in order to get the same expense ratio as the ETF. There are some other differences that matter to more active investors (e.g., intraday trading, options, etc.), but for a passive investor the ones above are the major ones. Apart from those mutual funds and ETFs are pretty similar. Personally, I prefer mutual funds because I'm at a point where the fund minimums aren't really an issue, and I don't want to deal with the more fiddly aspects of ETFs. For investors just starting out the lower minimum investment for an ETF is a big win, as long as you can get commission-free trades (which is what I've assumed above.)", "title": "" }, { "docid": "81304", "text": "You can look the Vanguard funds up on their website and view a risk factor provided by Vanguard on a scale of 1 to 5. Short term bond funds tend to get their lowest risk factor, long term bond funds and blended investments go up to about 3, some stock mutual funds are 4 and some are 5. Note that in 2008 Swenson himself had slightly different target percentages out here that break out the international stocks into emerging versus developed markets. So the average risk of this portfolio is 3.65 out of 5. My guess would be that a typical twenty-something who expects to retire no earlier than 60 could take more risk, but I don't know your personal goals or circumstances. If you are looking to maximize return for a level of risk, look into Modern Portfolio Theory and the work of economist Harry Markowitz, who did extensive work on the topic of maximizing the return given a set risk tolerance. More info on my question here. This question provides some great book resources for learning as well. You can also check out a great comparison and contrast of different portfolio allocations here.", "title": "" }, { "docid": "537394", "text": "If you are concerned about FDIC coverage, then yes, you can spread your money across multiple banks. The limit is $250k, so after you invest in property, 4 banks should do it. That having been said, in my opinion, it would be a waste to keep all this money in a bank's savings account. You will slowly lose value over time due to inflation. I suggest you spend a little money on an independent fee-based investment advisor. Choose someone who will teach you about investing in mutual funds, so you can feel comfortable with it. He or she should take into account your tolerance for risk, look at your goals, and help you come up with a low cost plan for investing your money. It's certainly okay to keep the money in a bank short-term, but don't wait too long; take steps toward putting that money to work for you.", "title": "" }, { "docid": "114054", "text": "\"I'm not following what's the meaning of \"\"open a mutual fund\"\". You don't open a mutual fund, you invest in it. There's a minimum required investment ($2000? Could be, some funds have lower limits, you don't have to go with the Fidelity one necessarily), but in general it has nothing to do with your Roth IRA account. You can invest in mutual funds with any trading account, not just Roth IRA (or any other specific kind). If you invest in ETF's - you can invest in funds just as well (subject to the minimums set). As to the plan itself - buying and selling ETF's will cost you commission, ~2-3% of your investment. Over several months, you may get positive returns, and may get negative returns, but keep in mind that you start with the 2-3% loss on day 1. Within a short period of time, especially in the current economic climate (which is very unstable - just out of recession, election year, etc etc), I would think that keeping the cash in a savings account would be a better choice. While with ETF you don't have any guarantees other than -3%, then with savings accounts you can at least have a guaranteed return of ~1% APY (i.e.: won't earn much over the course of your internship, but you'll keep your money safe for your long term investment). For the long term - the fluctuations of month to month don't matter much, so investing now for the next 50 years - you shouldn't care about the stock market going 10% in April. So, keep your 1000 in savings account, and if you want to invest 5000 in your Roth IRA - invest it then. Assuming of course that you're completely positive about not needing this money in the next several decades.\"", "title": "" }, { "docid": "282375", "text": "My suggestion is that you speak with a financial adviser that specializes in Islamic investing. For the long term there are Islam approved mutual funds that only invest in non-banking organizations, and I would assume there are more conservative options for the short term as well (3-4 years). Although you may not feel the effects of inflation all that much in just a few years, it would still be beneficial to utilize programs that allow you to earn a return on your money. (I may not have said that for $2,500 but for $25,000 I think it's worth looking into.) Also, some scholars suggest that it is even allowed to invest in mutual funds that deal with banks, as long as you calculate the portion of your return that came from the bank charging interest, and donate that amount to charity.", "title": "" }, { "docid": "549364", "text": "\"As you alluded to in your question, there is not one answer that will be true for all mutual funds. In fact, I would argue the question is not specific to mutual funds but can be applied to almost anyone who must make an investment decision: a mutual fund manager, hedge fund manager, or an individual investor. Even though money going into a company 401(k) retirement savings plan is typically automatically allocated to different funds as we have specified, this is generally not the case for other investment accounts. For example, I also have a Roth IRA in which I have some money from each paycheck direct deposited and it's up to me to decide whether to leave that money in cash or to invest it somewhere else. Every time you invest more money into a mutual fund, the fund manager has the same decision to make. There are two commonly used mutual fund figures that relate to your question: turnover rate, and cash reserves. Turnover rate measures the percent of a fund's portfolio that changes every year. For example, a turnover rate of 100% indicates that a fund replaces every asset it held at the beginning of the year with something else at the end of the year – funds with turnover rates greater than 100% average a holding period for a given asset of less than one year, and funds with turnover rates less than 100% average a holding period for a given asset of more than one year. Cash reserves simply measure the amount of money funds choose to keep as cash instead of investing in other assets. Another important distinction to make is between actively managed funds and passively managed funds. Passively managed funds are often referred to as \"\"index funds\"\" and have as their goal only to match the returns of a given index or some other benchmark. Actively managed funds on the other hand try to beat the market by exploiting so-called market inefficiencies; e.g. buying undervalued assets, selling overvalued assets, \"\"timing\"\" the market, etc. To answer your question for a specific fund, I would encourage you to look at the fund's prospectus. I take as one example of a passively managed fund the Vanguard 500 Index Fund (VFINX), a mutual fund that was created to track the S&P 500. In its prospectus, the fund states that, \"\"to track its target index as closely as possible, the Fund attempts to remain fully invested in stocks\"\". Furthermore, the prospectus states that \"\"the fund's daily cash balance may be invested in one or more Vanguard CMT Funds, which are very low-cost money market funds.\"\" Therefore, we would expect both this fund's turnover rate and cash reserves to be extremely low. When we look at its portfolio composition, we see this is true – it is currently at a 4.8% turnover rate and holds 0.0% in short term reserves. Therefore, we can assume this fund is regularly purchasing shares (similar to a dollar cost averaging strategy) instead of holding on to cash and purchasing shares together at a specific time. For actively managed funds, the picture will tend to look a little different. For example, if we look at the Magellan Fund's portfolio composition, we can see it has a turnover rate of 42%, and holds around .95% in cash/short term reserves. In this case, we can safely guess that trading activity may not be as regular as a passively managed fund, as an active manager attempts to time the market. You may find mutual funds that have much higher cash reserves – perhaps 10% or even more. Granted, it is impossible to know the exact trading strategy of a mutual fund, and for good reason – if we knew for example, that a fund purchases shares every day at 2:30PM in order to realign with the S&P 500, then sellers of S&P components could up the prices at that time to exploit the mutual fund's trade strategy. Large traders are constantly trying to find ways to conceal their actual trading activity in order to avoid these exact problems. Finally, I feel obligated to note that it is important to keep in mind that trade frequency is linked to transactions costs – in general, the more frequently an investment manager (whether it be you or a mutual fund manager) executes trades, the more that manager will lose in transactions costs.\"", "title": "" }, { "docid": "264820", "text": "\"An investment is sold when you sell that particular stock or fund. It doesn't wait until you withdraw cash from the brokerage account. Whether an investment is subject to long term or short term taxes depends on how long you held that particular stock. Sorry, you can't get around the higher short term tax by leaving the money in a brokerage account or re-investing in something else. If you are invested in a mutual fund, whether it's long or short term depends on when you buy and sell the fund. The fact that the fund managers are buying and selling behind your back doesn't affect this. (I don't know what taxes they have to pay, maybe you really are paying for it in the form of management fees or lower returns, but you don't explicitly pay the tax on these \"\"inner\"\" transactions.) Your broker should send you a tax statement every year giving the numbers that you need to fill in to the various boxes of your income tax form. You don't have to figure it out. Of course it helps to know the rules. If you've held a stock for 11 1/2 months and are planning to sell, you might want to consider waiting a couple of weeks so it becomes a long term capital gain rather than short term and thus subject to lower tax.\"", "title": "" }, { "docid": "157414", "text": "Let's look at some of your options: In a savings account, your $40,000 might be earning maybe 0.5%, if you are lucky. In a year, you'll have earned $200. On the plus side, you'll have your $40,000 easily accessible to you to pay for moving, closing costs on your new house, etc. If you apply it to your mortgage, you are effectively saving the interest on the amount for the life of the loan. Let's say that the interest rate on your mortgage is 4%. If you were staying in the house long-term, this interest would be compounded, but since you are only going to be there for 1 year, this move will save you $1600 in interest this year, which means that when you sell the house and pay off this mortgage, you'll have $1600 extra in your pocket. You said that you don't like to dabble in stocks. I wouldn't recommend investing in individual stocks anyway. A stock mutual fund, however, is a great option for investing, but only as a long-term investment. You should be able to beat your 4% mortgage, but only over the long term. If you want to have the $40,000 available to you in a year, don't invest in a mutual fund now. I would lean toward option #2, applying the money to the mortgage. However, there are some other considerations: Do you have any other debts, maybe a car loan, student loan, or a credit card balance? If so, I would forget everything else and put everything toward one or more of these loans first. Do you have an emergency fund in place, or is this $40,000 all of the cash that you have available to you? One rule of thumb is that you have 3 to 6 months of expenses set aside in a safe, easily accessible account ready to go if something comes up. Are you saving for retirement? If you don't already have retirement savings in place and are adding to it regularly, some of this cash would be a great start to a Roth IRA or something like that, invested in a stock mutual fund. If you are already debt free except for this mortgage, you might want to do some of each: Keep $10,000 in a savings account for an emergency fund (if you don't already have an emergency fund), put $5,000 in a Roth IRA (if you aren't already contributing a satisfactory amount to a retirement account), and apply the rest toward your mortgage.", "title": "" }, { "docid": "403701", "text": "This is really an extended comment on the last paragraph of @BenMiller's answer. When (the manager of) a mutual fund sells securities that the fund holds for a profit, or receives dividends (stock dividends, bond interest, etc.), the fund has the option of paying taxes on that money (at corporate rates) and distributing the rest to shareholders in the fund, or passing on the entire amount (categorized as dividends, qualified dividends, net short-term capital gains, and net long-term capital gains) to the shareholders who then pay taxes on the money that they receive at their own respective tax rates. (If the net gains are negative, i.e. losses, they are not passed on to the shareholders. See the last paragraph below). A shareholder doesn't have to reinvest the distribution amount into the mutual fund: the option of receiving the money as cash always exists, as does the option of investing the distribution into a different mutual fund in the same family, e.g. invest the distributions from Vanguard's S&P 500 Index Fund into Vanguard's Total Bond Index Fund (and/or vice versa). This last can be done without needing a brokerage account, but doing it across fund families will require the money to transit through a brokerage account or a personal account. Such cross-transfers can be helpful in reducing the amounts of money being transferred in re-balancing asset allocations as is recommended be done once or twice a year. Those investing in load funds instead of no-load funds should keep in mind that several load funds waive the load for re-investment of distributions but some funds don't: the sales charge for the reinvestment is pure profit for the fund if the fund was purchased directly or passed on to the brokerage if the fund was purchased through a brokerage account. As Ben points out, a shareholder in a mutual fund must pay taxes (in the appropriate categories) on the distributions from the fund even though no actual cash has been received because the entire distribution has been reinvested. It is worth keeping in mind that when the mutual fund declares a distribution (say $1.22 a share), the Net Asset Value per share drops by the same amount (assuming no change in the prices of the securities that the fund holds) and the new shares issued are at this lower price. That is, there is no change in the value of the investment: if you had $10,000 in the fund the day before the distribution was declared, you still have $10,000 after the distribution is declared but you own more shares in the fund than you had previously. (In actuality, the new shares appear in your account a couple of days later, not immediately when the distribution is declared). In short, a distribution from a mutual fund that is re-invested leads to no change in your net assets, but does increase your tax liability. Ditto for a distribution that is taken as cash or re-invested elsewhere. As a final remark, net capital losses inside a mutual fund are not distributed to shareholders but are retained within the fund to be written off against future capital gains. See also this previous answer or this one.", "title": "" }, { "docid": "269671", "text": "At your age (heck, at MY age :-)) I would not think about doing any of those types of investments (not savings) on your own, unless you are really interested in the investment process for its own sake, and are willing to devote a lot of time to investigating companies in order to try to pick good investments. Instead, find a good mutual fund from say Vanguard or TRP, put your money in there, and relax. Depending on your short-term goals (e.g. will you expect to need the money for college?) you could pick either an index fund, or a low-risk, mostly bond fund.", "title": "" }, { "docid": "43781", "text": "@Victor above has provided a very good answer, I shall try and highlight some differences. The differences are specific to a country, however, it does offer some insight regarding the difference between investing in retirement fund vis-a-vis investing in stock directly: In many countries the retirement fund is mandated by the govt. and has to be invested in (in form of direct deduction from salary) ~ Investing in stock is up to the individual In many cases (if not most) capital gain/interest accrual in retirement funds are not taxable ~ Depending upon current laws capital gain (long term/short term) from stocks are taxable Retirement funds are managed and are (in general) more stable in their returns ~ Returns from direct stock investments are dependent on investment decisions of the investor Retirement funds tend to, (though this is very country specific) return somewhat less than market, as an example, in India Public Provident Fund (PPF)/Employee Provident Fund (EPF) return 8.68% tax free ~ As for direct investment on stocks, Nifty has returned approx. 17% CAGR over 15-20 years. Given the above, if you can invest in stock by taking informed calls and you have a good understanding of the financial markets and their underpinning and (probably) looking at long term investment, then investing directly in stock could fetch returns that might not be paralled by retirement funds. If on the other hand, if you feel investing in stock is not for you, then it probably is better to stick with retirement funds and other low risk investments. Either way, you probably have to (and may be you should) carry some portion of your portfolio as retirement funds.", "title": "" }, { "docid": "405178", "text": "\"I would refer you to this question and answers. Here in the US we have two basic types of life insurance: term and whole life. Universal life is a marketing response to whole life being such a bad deal, and is whole life just not quite as bad. I am not familiar with the products in India, but given the acronym (ULIP), it is probably universal life, and as you describe is variable universal life. Likely Description \"\"Under the hood\"\", or in effect, you are purchasing a term life policy and investing excess premiums in a collection of stock mutual funds. This is a bad deal for a few reasons: A much better option is to buy \"\"level term insurance\"\" and invest on your own. You won't necessarily lose money, but you can make better financial decisions. It is good to invest, it is good to have life. A better decision would not to combine the two into a single product.\"", "title": "" }, { "docid": "524612", "text": "ETFs are a type of investment, not a specific choice. In other words, there are good ETFs and bad. What you see is the general statement that ETFs are preferable to most mutual funds, if only for the fact that they are low cost. An index ETF such as SPY (which reflects the S&P 500 index) has a .09% annual expense, vs a mutual fund which average a full percent or more. sheegaon isn't wrong, I just have a different spin to offer you. Given a long term return of say even 8% (note - this question is not a debate of the long term return, and I purposely chose a low number compared to the long term average, closer to 10%) and the current CD rate of <1%, a 1% hit for the commission on the buy side doesn't bother me. The sell won't occur for a long time, and $8 on a $10K sale is no big deal. I'd not expect you to save $1K/yr in cash/CDs for the years it would take to make that $8 fee look tiny. Not when over time the growth will overshaddow this. One day you will be in a position where the swings in the market will produce the random increase or decrease to your net worth in the $10s of thousands. Do you know why you won't lose a night's sleep over this? Because when you invested your first $1K, and started to pay attention to the market, you saw how some days had swings of 3 or 4%, and you built up an immunity to the day to day noise. You stayed invested and as you gained wealth, you stuck to the right rebalancing each year, so a market crash which took others down by 30%, only impacted you by 15-20, and you were ready for the next move to the upside. And you also saw that since mutual funds with their 1% fees never beat the index over time, you were happy to say you lagged the S&P by .09%, or 1% over 11 year's time vs those whose funds had some great years, but lost it all in the bad years. And by the way, right until you are in the 25% bracket, Roth is the way to go. When you are at 25%, that's the time to use pre-tax accounts to get just below the cuttoff. Last, welcome to SE. Edit - see sheegaon's answer below. I agree, I missed the cost of the bid/ask spread. Going with the lowest cost (index) funds may make better sense for you. To clarify, Sheehan points out that ETFs trade like a stock, a commission, and a bid/ask, both add to transaction cost. So, agreeing this is the case, an indexed-based mutual fund can provide the best of possible options. Reflecting the S&P (for example) less a small anual expense, .1% or less.", "title": "" }, { "docid": "161445", "text": "The S&P 500 is a stock market index, which is a list of 500 stocks from the largest companies in America. You could open a brokerage account with a broker and buy shares in each of these companies, but the easiest, least expensive way to invest in all these stocks is to invest in an S&P 500 index mutual fund. Inside an index mutual fund, your money will be pooled together with everyone else in the fund to purchase all the stocks in the index. These types of funds are very low expense compared to managed mutual funds. Most mutual fund companies have an S&P 500 index fund; two examples are Vanguard and Fidelity. The minimum investment in most of these mutual funds is low enough that you will be able to open an account with your $4000. Something you need to keep in mind, however: investing in any stock mutual fund is not non-risk. It's not even low-risk, really. It is very possible to lose money by investing in the stock market. An S&P 500 index fund is diversified in the sense that you have money in lots of different stocks, but it is also not diversified, in a sense, because it is all in large cap American stocks. Before investing in the stock market, you should have a goal for the money you are investing. If you are investing for something several years away, an index fund can be a good place to invest, but if you will need this money within the next few years, the stock market might be too risky for you.", "title": "" }, { "docid": "354136", "text": "\"This answer is applicable to the US. Similar rules may hold in some other countries as well. The shares in an open-ended (non-exchange-traded) mutual fund are not traded on stock exchanges and the \"\"market\"\" does not determine the share price the way it does for shares in companies as brokers make offers to buy and sell stock shares. The price of one share of the mutual fund (usually called Net Asset Value (NAV) per share) is usually calculated at the close of business, and is, as the name implies, the net worth of all the shares in companies that the fund owns plus cash on hand etc divided by the number of mutual fund shares outstanding. The NAV per share of a mutual fund might or might not increase in anticipation of the distribution to occur, but the NAV per share very definitely falls on the day that the distribution is declared. If you choose to re-invest your distribution in the same fund, then you will own more shares at a lower NAV per share but the total value of your investment will not change at all. If you had 100 shares currently priced at $10 and the fund declares a distribution of $2 per share, you will be reinvesting $200 to buy more shares but the fund will be selling you additional shares at $8 per share (and of course, the 100 shares you hold will be priced at $8 per share too. So, you will have 100 previous shares worth only $800 now + 25 new shares worth $200 for a total of 125 shares at $8 = $1000 total investment, just as before. If you take the distribution in cash, then you still hold the 100 shares but they are worth only $800 now, and the fund will send you the $200 as cash. Either way, there is no change in your net worth. However, (assuming that the fund is is not in a tax-advantaged account), that $200 is taxable income to you regardless of whether you reinvest it or take it as cash. The fund will tell you what part of that $200 is dividend income (as well as what part is Qualified Dividend income), what part is short-term capital gains, and what part is long-term capital gains; you declare the income in the appropriate categories on your tax return, and are taxed accordingly. So, what advantage is there in re-investing? Well, your basis in those shares has increased and so if and when you sell the shares, you will owe less tax. If you had bought the original 100 shares at $10 and sell the 125 shares a few years later at $11 and collect $1375, you owe (long-term capital gains) tax on just $1375-$1200 =$175 (which can also be calculated as $1 gain on each of the original 100 shares = $100 plus $3 gain on the 25 new shares = $175). In the past, some people would forget the intermediate transactions and think that they had invested $1000 initially and gotten $1375 back for a gain of $375 and pay taxes on $375 instead. This is less likely to occur now since mutual funds are now required to report more information on the sale to the shareseller than they used to in the past. So, should you buy shares in a mutual fund right now? Most mutual fund companies publish preliminary estimates in November and December of what distributions each fund will be making by the end of the year. They also usually advise against purchasing new shares during this period because one ends up \"\"buying a dividend\"\". If, for example, you bought those 100 shares at $10 on the Friday after Thanksgiving and the fund distributes that $2 per share on December 15, you still have $1000 on December 15, but now owe taxes on $200 that you would not have had to pay if you had postponed buying those shares till after the distribution was paid. Nitpickers: for simplicity of exposition, I have not gone into the detailed chronology of when the fund goes ex-dividend, when the distribution is recorded, and when cash is paid out, etc., but merely treated all these events as happening simultaneously.\"", "title": "" }, { "docid": "388252", "text": "\"(Congrats on earning/saving $3K and not wanting to blow it all on immediate gratification!) I currently have it invested in sector mutual funds but with the rise and fall of the stock market, is this really the best way to prepare long-term? Long-term? Yes! However... four years is not long term. It is, in fact, borderline short term. (When I was your age, that was incomprehensible too, but trust me: it's true.) The problem is that there's an inverse relationship between reward and risk: the higher the possible reward, the greater the risk that you'll lose a big chunk of it. I invest that middle-term money in a mix of junk high yield bond funds and \"\"high\"\" yield savings accounts at an online bank. My preferences are HYG purchased at Fidelity (EDIT: because it's commission-free and I buy a few hundred dollars worth every month), and Ally Bank.\"", "title": "" } ]
828	NAC inhibits the generation of angiotensin-converting enzyme.	[ { "docid": "4678846", "text": "CONTEXT The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear. OBJECTIVE To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography. DESIGN AND SETTING Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong. PARTICIPANTS Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention. INTERVENTION Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent. MAIN OUTCOME MEASURES Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. RESULTS Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P =.03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 micromol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 micromol/L]; 95% CI, 1.27-1.49 mg/dL; P =.006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001). The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P =.15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events. CONCLUSION Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.", "title": "Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial." } ]	[ { "docid": "1759213", "text": "OBJECTIVE To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system. DESIGN Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011. STUDY SELECTION Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes. RESULTS 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89). CONCLUSION Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.", "title": "The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis" }, { "docid": "26199970", "text": "Objective: It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life. Study design: Meta-analysis of published literature. Data sources: PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017. Study selection: Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration. Data synthesis: Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p < 0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15). Conclusions: Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.", "title": "Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials" }, { "docid": "14584755", "text": "The renin-angiotensin-aldosterone system plays a major role in the pathophysiology of hypertension and closely related cardio- and cerebrovascular events. Although both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) are equally important in the treatment of hypertension, according to the results of recent years, there might be substantial differences in their cardiovascular protective effects, and these differences might be explained by our increasing knowledge of their non-overlapping mechanisms of action. The number of studies investigating how ACE inhibitors and ARB agents differ will certainly be increasing in the future. ACE inhibitors are the safe therapeutic opportunity for hypertensive patients at high risk, with a cardiological comorbidity.", "title": "Differences in the Clinical Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Critical Review of the Evidence" }, { "docid": "6157837", "text": "Angiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs. Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies. Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia. This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent. Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures. The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient. Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion. Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs.1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system. When renal perfusion pressure falls (as in …", "title": "Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association." }, { "docid": "43417006", "text": "New-onset diabetes mellitus (NOD) refers to forms of diabetes mellitus that develop during the therapeutic processes of other diseases such as hypertension. This study has been conducted in a network meta-analysis to compare antihypertensive drugs by identifying both the advantages and disadvantages on NOD by focusing on their respective effect rates. Odd ratios and corresponding 95% confidence intervals or credible intervals were calculated within pairwise and network meta-analysis. A total of 38 articles with 224 140 patients were included to evaluate the preventive effect of hypertension drugs on NOD. From the network meta-analysis it was evident that both angiotensin-converting enzyme inhibitor as well as angiotensin receptor blocker treatments are associated with a lower risk of developing NOD compared with placebo, with ranking probabilities of 79.81% and 72.77%, respectively, while β-blockers and calcium channel blockers may significantly increase the probability of developing NOD (β-blockers: odds ratio, 2.18 [95% credible intervals: 1.36-3.50]; calcium channel blockers: odds ratio, 1.16 [95% credible intervals, 1.05-1.29]). In conclusion, angiotensin receptor blockers have an advantage over the other treatments regarding the NOD.", "title": "Comparative risk of new-onset diabetes mellitus for antihypertensive drugs: A network meta-analysis." }, { "docid": "4700428", "text": "BACKGROUND Relapse to cocaine seeking has been linked with low glutamate in the nucleus accumbens core (NAcore) causing potentiation of synaptic glutamate transmission from prefrontal cortex (PFC) afferents. Systemic N-acetylcysteine (NAC) has been shown to restore glutamate homeostasis, reduce relapse to cocaine seeking, and depotentiate PFC-NAcore synapses. Here, we examine the effects of NAC applied directly to the NAcore on relapse and neurotransmission in PFC-NAcore synapses, as well as the involvement of the metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5). METHODS Rats were trained to self-administer cocaine for 2 weeks and following extinction received either intra-accumbens NAC or systemic NAC 30 or 120 minutes, respectively, before inducing reinstatement with a conditioned cue or a combined cue and cocaine injection. We also recorded postsynaptic currents using in vitro whole cell recordings in acute slices and measured cystine and glutamate uptake in primary glial cultures. RESULTS NAC microinjection into the NAcore inhibited the reinstatement of cocaine seeking. In slices, a low concentration of NAC reduced the amplitude of evoked glutamatergic synaptic currents in the NAcore in an mGluR2/3-dependent manner, while high doses of NAC increased amplitude in an mGluR5-dependent manner. Both effects depended on NAC uptake through cysteine transporters and activity of the cysteine/glutamate exchanger. Finally, we showed that by blocking mGluR5 the inhibition of cocaine seeking by NAC was potentiated. CONCLUSIONS The effect of NAC on relapse to cocaine seeking depends on the balance between stimulating mGluR2/3 and mGluR5 in the NAcore, and the efficacy of NAC can be improved by simultaneously inhibiting mGluR5.", "title": "The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine." }, { "docid": "35724562", "text": "In adult patients with CKD, hypertension is linked to the development of left ventricular hypertrophy, but whether this association exists in children with CKD has not been determined conclusively. To assess the relationship between BP and left ventricular hypertrophy, we prospectively analyzed data from the Chronic Kidney Disease in Children cohort. In total, 478 subjects were enrolled, and 435, 321, and 142 subjects remained enrolled at years 1, 3, and 5, respectively. Echocardiograms were obtained 1 year after study entry and then every 2 years; BP was measured annually. A linear mixed model was used to assess the effect of BP on left ventricular mass index, which was measured at three different visits, and a mixed logistic model was used to assess left ventricular hypertrophy. These models were part of a joint longitudinal and survival model to adjust for informative dropout. Predictors of left ventricular mass index included systolic BP, anemia, and use of antihypertensive medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Predictors of left ventricular hypertrophy included systolic BP, female sex, anemia, and use of other antihypertensive medications. Over 4 years, the adjusted prevalence of left ventricular hypertrophy decreased from 15.3% to 12.6% in a systolic BP model and from 15.1% to 12.6% in a diastolic BP model. These results indicate that a decline in BP may predict a decline in left ventricular hypertrophy in children with CKD and suggest additional factors that warrant additional investigation as predictors of left ventricular hypertrophy in these patients.", "title": "BP control and left ventricular hypertrophy regression in children with CKD." }, { "docid": "32463364", "text": "OBJECTIVES Prevention of cognitive decline and dementia with blood pressure lowering treatments has shown inconsistent results. We compared the effects of different classes of antihypertensive drugs on the incidence of dementia, and on cognitive function. METHODS We conducted a systematic review and included 19 randomized trials (18 515 individuals) and 11 studies (831 674 individuals) analysing the effects of antihypertensive treatment on cognition and on the incidence of dementia, respectively, in hypertensive patients without prior cerebrovascular disorders. Network meta-analysis was used for the comparison of antihypertensive classes. RESULTS Antihypertensive treatment, regardless of the drug class, had benefits on overall cognition [effect size 0.05, 95% confidence interval (CI) 0.02-0.07] and all cognitive functions except language. Antihypertensive treatment reduced the risk of all-cause dementia by 9%, with reference to the control group (hazard ratio 0.91, 95% CI 0.89-0.94), when randomized trials and observationnal studies were combined (n = 15). Result was not significant with randomized trials alone (n = 4). Angiotensin II receptor blockers (ARBs) had larger benefits than placebo on overall cognition (adjusted effect size 0.60 ± 0.18, P = 0.02). ARBs were more effective than β-blockers (0.67 ± 0.18, P = 0.01), diuretics (0.54 ± 0.19, P = 0.04) and angiotensin-converting enzyme inhibitors (0.47 ± 0.17, P = 0.04) in rank. The mean change in blood pressure did not differ significantly between the different antihypertensive drug classes. CONCLUSION Our results support the notion that antihypertensive treatment has beneficial effects on cognitive decline and prevention of dementia, and indicate that these effects may differ between drug classes with ARBs possibly being the most effective.", "title": "Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis." }, { "docid": "26025370", "text": "Background: Vasoconstriction and reactive oxygen species (ROS) accumulation following contrast media (CM) injection are the key factors triggering CM-induced nephropathy. We compared the effects of N-acetylcysteine (NAC), theophylline or sodium bicarbonate on intrarenal vasoconstriction and ROS generation in a rat model of CM-induced nephropathy. Methods: Following a 3-day dehydration, Sprague-Dawley rats received CM (Telebrix) or sham ‘CM’ injection of 0.9% saline. Part of them received NAC, theophylline or bicarbonate prior to CM. Medullar renal blood flow was estimated by laser Doppler. The animals were sacrificed 1, 15 or 30 min after the respective treatments, their kidneys allocated and intrarenal STAT-8 isoprostane, PGE2 and NO assessed. Results: Vasoconstriction was significantly attenuated by NAC. Theophylline only mildly attenuated the perfusion drop at 15 min, and was ineffective following 30 min. Unlike theophylline or bicarbonate, NAC significantly augmented intrarenal PGE2. NAC, theophylline but not bicarbonate, gradually increased intrarenal NO. In all experimental variables, CM-induced ROS accumulation, represented by STAT-8 isoprostane estimation, progressed undisturbed. Conclusions: (1) CM-induced intrarenal vasoconstriction was efficiently prohibited by NAC but not bicarbonate or theophylline; (2) the vasodilatory effect of NAC was mediated via increased PGE2 synthesis, and (3) ROS accumulation was a primary renal response to CM-induced injury, not affected by any pharmacologic manipulations.", "title": "Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction" }, { "docid": "6397191", "text": "Endothelin-1 (ET-1) is the predominant endothelin isopeptide generated by the vascular wall and therefore appears to be the most important peptide involved in regulation of cardiovascular events. Many pathologic conditions are associated with elevations of ET-1 in the blood vessel wall. Because these conditions are often cytokine driven, we examined the effects of a mixture of cytokines on ET-1 production in human vascular smooth muscle cells (VSMCs) derived from internal mammary artery and saphenous vein (SV). Incubation of IMA and SV VSMCs with tumor necrosis factor-alpha (10 ng/ml) and interferon-gamma (1000 U/ml) in combination for up to 48 h markedly elevated the expression of mRNA for prepro-ET-1 and the release of ET-1 into the culture medium. This cytokine-stimulated release of ET-1 was inhibited by a series of dual endothelin-converting enzyme (ECE)/neutral endopeptidase inhibitors, phosphoramidon, CGS 26303, and CGS 26393, with an accompanying increase in big ET-1 release but with no effect on expression of mRNA for prepro-ET-1. These same compounds were 10 times more potent at inhibiting the conversion of exogenously applied big ET-1 to ET-1. ECE-1b/c mRNA is present in SV VSMCs, however no ECE-1a is present in these cells. Thus VSMCs most probably contain, like endothelial cells, an intracellular ECE responsible for the endogenous synthesis of ET-1. Under the influence of pro-inflammatory mediators the vascular smooth muscle can therefore become an important site of ET-1 production, as has already been established for the dilator mediators nitric oxide, prostaglandin I2, and prostaglandin E2.", "title": "Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme." }, { "docid": "7821634", "text": "Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ∼30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.", "title": "Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance" }, { "docid": "25816994", "text": "BACKGROUND Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.", "title": "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial." }, { "docid": "38944245", "text": "Lung Krüppel-like factor (LKLF/KLF2) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro. We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridization and laser microbeam microdissection/reverse transcriptase-polymerase chain reaction in a murine carotid artery collar model, in which a 4- to 30-fold induction of LKLF occurred at the high-shear sites. Dissection of the biomechanics of LKLF regulation in vitro demonstrated that steady flow and pulsatile flow induced basal LKLF expression 15- and 36-fold at shear stresses greater than approximately 5 dyne/cm2, whereas cyclic stretch had no effect. Prolonged LKLF induction in the absence of flow changed the expression of angiotensin-converting enzyme, endothelin-1, adrenomedullin, and endothelial nitric oxide synthase to levels similar to those observed under prolonged flow. LKLF repression by siRNA suppressed the flow response of endothelin-1, adrenomedullin, and endothelial nitric oxide synthase (P < 0.05). Thus, we demonstrate that endothelial LKLF is regulated by flow in vivo and is a transcriptional regulator of several endothelial genes that control vascular tone in response to flow.", "title": "Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes." }, { "docid": "5573975", "text": "Molecules associated with the transforming growth factor β (TGF-β) superfamily, such as bone morphogenic proteins (BMPs) and TGF-β, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-β1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR-123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis.", "title": "Activin–like kinase–3 activity is important for kidney regeneration and reversal of fibrosis" }, { "docid": "3831884", "text": "Cancer cells have metabolic dependencies that distinguish them from their normal counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.", "title": "Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway" }, { "docid": "14121786", "text": "BACKGROUND Epidemiologic analysis of family data on blood pressure (BP) is often compromised by the effects of antihypertensive medications. A review of numerous clinical trials that investigated the effects of BP-lowering medications is summarized here. METHODS Published clinical trials, including 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies with a total of 11,739 participants, were reviewed from PubMed. Six major classes/groups of antihypertensive medications were categorized by ethnicity, including angiotensin-converting enzyme (ACE) inhibitors, alpha1-blockers, cardioselective beta-blockers (beta1-blockers), calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics. RESULTS Using sitting or supine BP, for ethnic groups combined, monodrug therapy with ACE inhibitors showed a weighted average effect of lowering the systolic and diastolic BP by 12.5/9.5 mm Hg; alpha1-blockers by 15.5/11.7 mm Hg; beta1-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. However, ACE inhibitors, alpha1-blockers, and beta1-blockers were less effective in African Americans than in non-African Americans, whereas calcium channel blockers, thiazide diuretics, and loop diuretics were more effective in African Americans than in non-African Americans. For two-drug combination therapy with ethnic groups combined, the BP-lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic BP, respectively. CONCLUSIONS The BP-lowering effects reported here may be used to impute the pretreatment BP levels, which can improve the information content and hence the power of epidemiologic analysis in studies where use of antihypertensive medications is a confounding factor in the BP measurements.", "title": "A summary of the effects of antihypertensive medications on measured blood pressure." }, { "docid": "35345807", "text": "Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD(+) concentration through the combined action of NAD(+) biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD(+) precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD(+) salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD(+) concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD(+). The INAM-induced increase in NAD(+) was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD(+) salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD(+). We also provide evidence suggesting that INAM influences the expression of multiple NAD(+) biosynthesis and salvage pathways to promote homeostasis during stationary phase.", "title": "Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration." }, { "docid": "3669694", "text": "Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling. Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells before and after reprogramming, the role of specific chromatin-modifying enzymes in reprogramming remains to be determined. To address how chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways, and identified positive and negative modulators of iPSC generation. Whereas inhibition of the core components of the polycomb repressive complex 1 and 2, including the histone 3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated reprogramming, significantly increased the yield of iPSC colonies, and substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in the reprogramming process is associated with a marked increase in two alternative factors, NANOG and LIN28, which play essential functional roles in the enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution revealed that fibroblast-specific genes associated with the epithelial to mesenchymal transition lose H3K79me2 in the initial phases of reprogramming. DOT1L inhibition facilitates the loss of this mark from genes that are fated to be repressed in the pluripotent state. These findings implicate specific chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and demonstrate how modulation of chromatin-modifying enzymes can be exploited to more efficiently generate iPSCs with fewer exogenous transcription factors.", "title": "Chromatin modifying enzymes as modulators of reprogramming" }, { "docid": "45770026", "text": "Eicosapentaenoic acid (EPA) has beneficial effects in many inflammatory disorders. In this study, dietary EPA was converted to 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) by ω-3 epoxygenation in the mouse peritoneal cavity. Mediator lipidomics revealed a series of novel oxygenated metabolites of 17,18-EpETE, and one of the major metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE), displayed a potent anti-inflammatory action by limiting neutrophil infiltration in murine zymosan-induced peritonitis. 12-OH-17,18-EpETE inhibited leukotriene B4-induced neutrophil chemotaxis and polarization in vitro in a low nanomolar range (EC50 0.6 nM). The complete structures of two natural isomers were assigned as 12S-OH-17R,18S-EpETE and 12S-OH-17S,18R-EpETE, using chemically synthesized stereoisomers. These natural isomers displayed potent anti-inflammatory action, whereas the unnatural stereoisomers were essentially devoid of activity. These results demonstrate that 17,18-EpETE derived from dietary EPA is converted to a potent bioactive metabolite 12-OH-17,18-EpETE, which may generate an endogenous anti-inflammatory metabolic pathway.", "title": "Eicosapentaenoic acid is converted via ω-3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid." }, { "docid": "2086909", "text": "The Tet family of enzymes (Tet1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Mouse embryonic stem cells (mESCs) highly express Tet1 and have an elevated level of 5hmC. Tet1 has been implicated in ESC maintenance and lineage specification in vitro but its precise function in development is not well defined. To establish the role of Tet1 in pluripotency and development, we have generated Tet1 mutant mESCs and mice. Tet1(-/-) ESCs have reduced levels of 5hmC and subtle changes in global gene expression, and are pluripotent and support development of live-born mice in tetraploid complementation assay, but display skewed differentiation toward trophectoderm in vitro. Tet1 mutant mice are viable, fertile, and grossly normal, though some mutant mice have a slightly smaller body size at birth. Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development.", "title": "Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development." }, { "docid": "27428509", "text": "Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or β-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the β cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3–6 years, compared with a thiazide diuretic, β-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or β1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14–34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.", "title": "Prevention of Type 2 Diabetes Mellitus Through Inhibition of the Renin-Angiotensin System" }, { "docid": "3866315", "text": "Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with ω-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 ω-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX5 and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue > 5,12,18R-triHEPE > 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as ω-5 and ω-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2–nonsteroidal antiinflammatory drug–dependent oxygenations and cell–cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of ω-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.", "title": "Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2–Nonsteroidal Antiinflammatory Drugs and Transcellular Processing" }, { "docid": "4447055", "text": "Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting. Protein tyrosine phosphatase σ (PTPσ), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. Here we find in rats that PTPσ has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTPσ wedge domain that binds to PTPσ and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTPσ in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.", "title": "Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury" }, { "docid": "4405194", "text": "Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells. Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.", "title": "Induction of human neuronal cells by defined transcription factors" }, { "docid": "18348376", "text": "BACKGROUND Multiple mechanisms have been advanced to account for CD4+FOXP3+ regulatory T cell (Treg)-mediated suppression of CD4+ effector T cells (Teffs) but none appear to completely explain suppression. Previous data indicates that Tregs may affect the microenvironment redox state. Given the inherent redox sensitivity of T cells, we tested the hypothesis that oxidants may mediate the direct suppression of Teffs by Tregs. METHODOLOGY/PRINCIPAL FINDINGS Tregs and Teffs were isolated from the spleens of wild type (WT) C57BL/6 mice or Ncf1(p47phox)-deficient C57BL/6 mice which lack NADPH oxidase function. Teffs were labeled with CFSE and co-cultured with unlabeled Tregs at varying Treg:Teff ratios in the presence of anti-CD3/CD28 coated beads for 3 days in suppression assays. Treg-mediated suppression was quantified by flow cytometric analysis of CFSE dilution in Teffs. The presence of the antioxidants n-acetylcysteine (NAC) or 2-mercaptoethanol or inhibitors of NADPH oxidase (diphenyleneiodonium and VAS-2870) resulted in reduced WT Treg-mediated suppression. The observed suppression was in part dependent upon TGFβ as it was partially blocked with neutralizing antibodies. The suppression of Teff proliferation induced by exogenous TGFβ treatment could be overcome with NAC. Ncf1-deficient Teff were slightly but significantly less sensitive than WT Teff to suppression by exogenous TGFβ. Ncf1-deficient Tregs suppressed Ncf1-deficient Teff very poorly compared to wild type controls. There was partial but incomplete reconstitution of suppression in assays with WT Tregs and Ncf1-deficient Teff. CONCLUSIONS/SIGNIFICANCE We present evidence that NADPH oxidase derived ROS plays a role in the direct Treg mediated suppression of CD4+ effector T cells in a process that is blocked by thiol-containing antioxidants, NADPH oxidase inhibitors or a lack of Ncf1 expression in Tregs and Teffs. Oxidants may represent a potential new target for therapeutic modulation of Treg function.", "title": "Ncf1 (p47phox) Is Essential for Direct Regulatory T Cell Mediated Suppression of CD4+ Effector T Cells" }, { "docid": "44030361", "text": "Accumulated evidence suggests that an altered ambulatory blood pressure (BP) profile, particularly elevated nighttime BP, reflects target organ injury and is a better predictor of further cardiorenal risk than the clinic BP or daytime BP in hypertensive patients complicated by chronic kidney disease (CKD). In this study, we examined the beneficial effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on ambulatory BP profiles and renal function in hypertensive CKD patients. Forty-six patients were randomly assigned to the olmesartan add-on group (n=23) or the non-ARB group (n=23). At baseline and after the 16-week treatment period, ambulatory BP monitoring was performed and renal function parameter measurements were collected. Although the baseline clinic BP levels and the after-treatment/baseline (A/B) ratios of clinic BP levels were similar in the olmesartan add-on and non-ARB groups, the A/B ratios of ambulatory 24-h and nighttime BP levels in the olmesartan add-on group were significantly lower. Furthermore, the A/B ratios of urinary protein, albumin and type IV collagen excretion in the olmesartan add-on group were significantly lower than those in the non-ARB group (urinary protein excretion, 0.72±0.41 vs. 1.45±1.48, P=0.030; urinary albumin excretion, 0.73±0.37 vs. 1.50±1.37, P=0.005; urinary type IV collagen excretion, 0.87±0.42 vs. 1.48±0.87, P=0.014) despite comparable A/B ratios for the estimated glomerular filtration rate in the two groups. These results indicate that in hypertensive patients with CKD, olmesartan add-on therapy improves the ambulatory BP profile via a preferential reduction in nighttime BP with concomitant renal injury inhibition.", "title": "The angiotensin II type 1 receptor blocker olmesartan preferentially improves nocturnal hypertension and proteinuria in chronic kidney disease" }, { "docid": "5849439", "text": "Microsporogenesis has been examined in wild-type Arabidopsis thaliana and the nuclear male-sterile mutant BM3 by cytochemical staining. The mutant lacks adenine phosphoribosyltransferase, an enzyme of the purine salvage pathway that converts adenine to AMP. Pollen development in the mutant began to diverge from wild type just after meiosis, as the tetrads of microspores were released from their callose walls. The first indication of abnormal pollen development in the mutant was a darker staining of the microspore wall due to an incomplete synthesis of the intine. Vacuole formation was delayed and irregular in the mutant, and the majority of the mutant microspores failed to undergo mitotic divisions. Enzyme activities of alcohol dehydrogenase and esterases decreased in the mutant soon after meiosis and were undetectable in mature pollen grains of the mutant. RNA accumulation was also diminished. These results are discussed in relation to the possible role(s) of adenine salvage in pollen development.", "title": "Cytochemical Analysis of Pollen Development in Wild-Type Arabidopsis and a Male-Sterile Mutant." }, { "docid": "10284593", "text": "Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO-deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3-chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation.", "title": "Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation" }, { "docid": "13777138", "text": "TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs.", "title": "Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells." }, { "docid": "17546486", "text": "Skeletal muscle overload induces the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2, leading to new capillary growth. We found that the overload-induced increase in angiogenesis, as well as increases in VEGF, MMP-2 and MT1-MMP transcripts were abrogated in muscle VEGF KO mice, highlighting the critical role of myocyte-derived VEGF in controlling this process. The upstream mediators that contribute to overload-induced expression of VEGF have yet to be ascertained. We found that muscle overload increased angiotensinogen expression, a precursor of angiotensin (Ang) II, and that Ang II signaling played an important role in basal VEGF production in C2C12 cells. Furthermore, matrix-bound VEGF released from myoblasts induced the activation of endothelial cells, as evidenced by elevated endothelial cell phospho-p38 levels. We also found that exogenous Ang II elevates VEGF expression, as well as MMP-2 transcript levels in C2C12 myotubes. Interestingly, these responses also were observed in skeletal muscle endothelial cells in response to Ang II treatment, indicating that these cells also can respond directly to the stimulus. The involvement of Ang II in muscle overload-induced angiogenesis was assessed. We found that blockade of AT1R-dependent Ang II signaling using losartan did not attenuate capillary growth. Surprisingly, increased levels of VEGF protein were detected in overloaded muscle from losartan-treated rats. Similarly, we observed elevated VEGF production in cultured endothelial cells treated with losartan alone or in combination with Ang II. These studies conclusively establish the requirement for muscle derived VEGF in overload-induced angiogenesis and highlight a role for Ang II in basal VEGF production in skeletal muscle. However, while Ang II signaling is activated following overload and plays a role in muscle VEGF production, inhibition of this pathway is not sufficient to halt overload-induced angiogenesis, indicating that AT1-independent signals maintain VEGF production in losartan-treated muscle.", "title": "Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells" } ]
5a8cfc79554299585d9e378e	Which campaign in the Second World War lasted from June 1940 to 13 May 1943 and included the Operation Torch?	[ { "docid": "73236", "text": "Operation Torch (initially called Operation Gymnast) was the British-United States invasion of French North Africa during the North African Campaign of the Second World War which started on 8 November 1942.", "title": "" }, { "docid": "493688", "text": "The North African Campaign of the Second World War took place in North Africa from 10 June 1940 to 13 May 1943. It included campaigns fought in the Libyan and Egyptian deserts (Western Desert Campaign, also known as the Desert War) and in Morocco and Algeria (Operation Torch) and Tunisia (Tunisia Campaign).", "title": "" } ]	[ { "docid": "14819361", "text": "V Corps was a corps-sized formation of the British Army that saw service in both World War I and World War II. It was first organised in February 1915 and fought through World War I on the Western front. It was recreated in June 1940 during World War II and substantially reorganised in 1942 for participation in Operation Torch. It fought through the Tunisia Campaign and later the Italian Campaign.", "title": "" }, { "docid": "902095", "text": "The Siege of Tobruk lasted for 241 days in 1941, after Axis forces advanced through Cyrenaica from El Agheila in Operation Sonnenblume against Allied forces in Libya, during the Western Desert Campaign (1940–1943) of the Second World War.", "title": "" }, { "docid": "18756772", "text": "Spike Milligan's second volume of war autobiography, \"Rommel?\" \"Gunner Who?\": A Confrontation in the Desert, was published in 1974, with Jack Hobbs credited as an editor. This book spans events from January to May 1943, during Operation Torch the Allied invasion of Morocco and Algeria and the Tunisia Campaign in World War II. (The preface to the earlier book states this would be a trilogy but he wrote seven volumes.)", "title": "" }, { "docid": "201680", "text": "Field Marshal Archibald Percival Wavell, 1st Earl Wavell, {'1': \", '2': \", '3': \", '4': \"} (5 May 1883 – 24 May 1950) was a senior officer of the British Army. He served in the Second Boer War, the Bazar Valley Campaign and the Great War, during which he was wounded in the Second Battle of Ypres. He served in the Second World War, initially as Commander-in-Chief Middle East, in which role he led British forces to victory over the Italians in western Egypt and eastern Libya during Operation \"Compass\" in December 1940, only to be defeated by the German Army in the Western Desert in April 1941. He served as Commander-in-Chief, India, from July 1941 until June 1943 (apart from a brief tour as Commander of ABDACOM) and then served as Viceroy of India until his retirement in February 1947.", "title": "" }, { "docid": "974260", "text": "The Africa Star is a military campaign medal, instituted by the United Kingdom on 8 July 1943 for award to subjects of the British Commonwealth who served in the Second World War, specifically in North Africa between 10 June 1940 and 12 May 1943 inclusive.", "title": "" }, { "docid": "2384429", "text": "The Bougainville Campaign was a series of land and naval battles of the Pacific campaign of World War II between Allied forces and the Empire of Japan. It was part of Operation Cartwheel, the Allied grand strategy in the South Pacific. The campaign took place in the Northern Solomons in two phases. The first phase, in which American troops invaded and held the perimeter around the beachhead at Torokina, lasted from November 1943 through November 1944. The second phase, in which primarily Australian troops went on the offensive, mopping up pockets of starving, isolated but still-determined Japanese, lasted from November 1944 until August 1945, when the last Japanese on the island surrendered. Operations during the final phase of the campaign saw the Australian forces advance north towards the Bonis Peninsula and south towards the main Japanese stronghold around Buin, although the war ended before these two enclaves were completely destroyed.", "title": "" }, { "docid": "1275948", "text": "Operation Royal Marine was a military operation in May 1940 during the Second World War, in the Battle of France (10 May – 25 June 1940). \"Fluvial\" mines were floated down rivers from France into Germany, to destroy bridges, barges and other water transport. After several postponements insisted on by the French government, fearful of German retaliation, the operation began on 10 May 1940, when the German offensive in the west began. The mines caused some damage and delay to German river traffic on the Rhine, from Karlsruhe to Koblenz and damaged bridges and protective barriers. Part of the plan was for Royal Air Force (RAF) bombers to drop the mines into rivers and canals on moonlit nights but this had hardly begun when the campaign ended. The success of the plot was nullified by the Allied defeat and the Franco-German Armistice of 22 June 1940.", "title": "" }, { "docid": "27063742", "text": "The No. 1 Commando was a unit of the British Commandos and part of the British Army during the Second World War. It was raised in 1940 from the ranks of the existing independent companies. Operationally they carried out a series of small scale cross channel raids and spearheaded the Operation Torch landings in North Africa. They were then sent to the India as part of the 3rd Commando Brigade and took part in operations in the Burma Campaign. During the Second World War only eight commandos were recipients of the Victoria Cross two of the eight were from No. 1 Commando. After the war they were sent to reoccupy Hong Kong before being amalgamated with No. 5 Commando and became known as No. 1/5 Commando. The amalgamated No. 1/5 Commando was disbanded in 1947.", "title": "" }, { "docid": "206146", "text": "Operation Compass was the first large Allied military operation of the Western Desert Campaign (1940–1943) during the Second World War. British and other Commonwealth forces attacked Italian forces in western Egypt and Cyrenaica, the eastern province of Libya, from December 1940 to February 1941, with great success. The Western Desert Force (Lieutenant-General Richard O'Connor) with about 30,000 men, advanced from Mersa Matruh in Egypt on a five-day raid against the Italian positions of the 10th Army (Marshal Rodolfo Graziani), which had about 150,000 men in fortified posts around Sidi Barrani and in Cyrenaica.", "title": "" }, { "docid": "36389825", "text": "The 2/23rd Battalion was an infantry battalion of the Australian Army, which served during the Second World War. Formed in June 1940 from primarily volunteers from Albury, New South Wales, the battalion served in North Africa in 1941–1942 as part of the 26th Brigade, which was assigned to the 7th Division, before being reassigned to the 9th Division. In early 1943, the battalion returned to Australia and later took part in campaigns against the Japanese in New Guinea in 1943–1944 and Borneo in 1945, before being disbanded in 1946.", "title": "" }, { "docid": "14514560", "text": "Admiral of the Fleet Sir Algernon Usborne Willis (17 May 1889 – 12 April 1976) was a Royal Navy officer. He served in the First World War and saw action at the Battle of Jutland in May 1916. He also served in the Second World War as Commander-in-Chief, South Atlantic in which capacity he led actions against German and Japanese raiding ships. He continued his war service as Flag Officer commanding 3rd Battle Squadron and Second in command of the Eastern Fleet and then as Flag Officer commanding Force H, the force which covered North African Operations, the Allied invasion of Sicily in July 1943 and then the Allied invasion of Italy in September 1943. He spent the final years of the war as Commander-in-Chief, Levant, in which capacity he conducted naval operations in support of the Dodecanese Campaign, and then as Second Sea Lord, in which capacity he arranged the manpower for the campaign in the Pacific Ocean against the Imperial Japanese Navy. After the war he served as Commander-in-Chief, Mediterranean Fleet, in which role he was faced with unrest in Mandatory Palestine, before he became Commander-in-Chief, Portsmouth.", "title": "" }, { "docid": "28146382", "text": "An Independent Company was a formation of the British Army during the Second World War. Initially there were ten Independent Companies, who were raised from volunteers from Territorial Army divisions in April 1940. They were intended for guerrilla-style operations in the Allied campaign in Norway. The companies were disbanded after returning to Britain at the end of the campaign but another company, No. 11 Company, was formed from volunteers from the first ten Independent Companies on 14 June 1940, and took part in the first British commando raid, Operation Collar", "title": "" }, { "docid": "725531", "text": "The 6th Division was an infantry division of the Australian Army. It was raised briefly in 1917 during World War I, but was broken up to provide reinforcements before seeing action. It was not re-raised until the outbreak of World War II, when it was formed as a unit of the Second Australian Imperial Force (2nd AIF). Throughout 1940–1941 it served in the North African Campaign, the Greek campaign, on Crete and in Syria, fighting against the Germans, Italians and Vichy French. In 1942, the division left the Middle East and returned to Australia to meet the threat of Japan's entry into the war. Part of the division garrisoned Ceylon for a short period of time, before the division was committed to the New Guinea campaign. In New Guinea, its component brigades had a major role in the successful counter-offensive along the Kokoda Track, at Buna–Gona and around Salamaua–Lae in 1942–1943. Throughout late 1943–1944, the division was re-organised in Australia before being committed as a complete formation to one of the last Australian operations of the war around Aitape–Wewak in 1944–1945.", "title": "" }, { "docid": "29137424", "text": "Lom prisoner of war camp (Norwegian: \"Lom krigsfangeleir\" ) was a facility used by the Norwegian 2nd Division to hold German prisoners-of-war during the 1940 Norwegian Campaign of the Second World War. The camp, which operated from 20 to 27 April 1940, also held Norwegians accused of collaborating with the Germans or the Norwegians fascists led by Vidkun Quisling.", "title": "" }, { "docid": "10753304", "text": "The Dodecanese campaign of World War II was an attempt by Allied forces to capture the Italian-held Dodecanese islands in the Aegean Sea following the surrender of Italy in September 1943, and use them as bases against the German-controlled Balkans. Operating without air cover, the Allied effort failed, with the whole of the Dodecanese falling to the Germans within two months, and the Allies suffering heavy losses in men and ships. The Dodecanese campaign, lasting from 8 September to 22 November 1943, resulted in one of the last big German victories in the war.", "title": "" }, { "docid": "493696", "text": "The Italian Campaign of World War II was the name of Allied operations in and around Italy, from 1943 to the end of the war in Europe. Joint Allied Forces Headquarters (AFHQ) was operationally responsible for all Allied land forces in the Mediterranean theatre, and it planned and commanded the invasion of Sicily in July 1943, followed shortly thereafter in September by the invasion of the Italian mainland and the campaign on Italian soil until the surrender of the German Armed Forces in Italy in May 1945.", "title": "" }, { "docid": "11455647", "text": "Baby Blitz or Operation Steinbock (German: \"Unternehmen Steinbock\" ) was a strategic bombing campaign by the German air force (the Luftwaffe) during the Second World War. It targeted southern England and lasted from January to May 1944. Steinbock was the last strategic air offensive by the German bomber arm during the conflict.", "title": "" }, { "docid": "342691", "text": "Operation Alphabet was an evacuation, authorized on May 24, 1940, of Allied (British, French and Polish) troops from the harbour of Narvik in northern Norway marking the success of Nazi Germany's Operation Weserübung of April 9 and the end of the Allied campaign in Norway during World War II. The evacuation was completed by June 8.", "title": "" }, { "docid": "4170780", "text": "The Interim Peace (Finnish: \"Välirauha\" , Swedish: \"Mellanfreden\" ) was a short period in the history of Finland during the Second World War. The term is used for the time between the Winter War and the Continuation War, lasting a little over a year, from 13 March 1940 to 24 June 1941. The Moscow Peace Treaty was signed by Finland and the Soviet Union on 12 March 1940 and it ended the 105-day Winter War.", "title": "" }, { "docid": "4888983", "text": "The 6th Armoured Division was an armoured division of the British Army, created in September 1940 during World War II. The unit was initially supplied with Matilda and Valentine tanks, which were replaced by Crusader tanks and then finally with the M4 Sherman tank. It participated in the Operation Torch assault landings in Algeria and Morocco in November 1942 and saw its first action as part of V Corps of the British First Army in the Tunisia Campaign. After Tunisia, it participated in the Italian Campaign as part of the British Eighth Army and ended the war in Austria, again under the command of V Corps.", "title": "" }, { "docid": "31113065", "text": "Ole Jacob Bangstad (9 April 1917 – 2 June 2010) was a Norwegian military officer and sports official. During World War II he participated in the Norwegian Campaign in Trøndelag and Northern Norway in 1940, was leader of the first Norwegian parachute company in Great Britain from 1943 to 1945, and leader of railway sabotage operations at the Nordland Line in 1945. He continued his military career after the war, a Major General from 1964 and appointed \"generalinspektør for Hæren\" from 1971 to 1979.", "title": "" }, { "docid": "253769", "text": "Operation Cycle is the name of the evacuation of Allied troops from Le Havre, in the Pays de Caux of Upper Normandy from 10–13 June 1940, towards the end of the Battle of France, during the Second World War. The operation was preceded by the better known rescue of 338,226 British and French soldiers from Dunkirk in Operation Dynamo (26 May – 4 June). On 20 May, the Germans had captured Abbeville at the mouth of the Somme and cut off the main Allied armies in the north. South of the river, the Allies improvised defences and made local counter-attacks, to dislodge the Germans from bridgeheads on the south bank and re-capture river crossings for an advance northwards to regain contact with the armies in northern France and Flanders.", "title": "" }, { "docid": "22001120", "text": "Virgil Paul Brennan, (6 March 1920 – 13 June 1943), also known as Paul Brennan, was an Australian aviator and flying ace of the Second World War. Enlisting in the Royal Australian Air Force in November 1940, he briefly served in the European Theatre before transferring to Malta. Over the next five months, Brennan was officially credited with the destruction of 10 Axis aircraft from a total of twenty-four operational sorties. Reposted to England, he was assigned as a flying instructor and collaborated in the writing of \"Spitfires over Malta\", a book about his experiences on the island. Returning to Australia during 1943, Brennan was killed in a flying accident at Garbutt, Queensland, in June that year.", "title": "" }, { "docid": "228080", "text": "The Battle of France, also known as the Fall of France, was the German invasion of France and the Low Countries during the Second World War. In six weeks from 10 May 1940, German forces defeated Allied forces by mobile operations and conquered France, Belgium, Luxembourg and the Netherlands, bringing land operations on the Western Front to an end until 6 June 1944. Italy entered the war on 10 June 1940 and attempted an invasion of France.", "title": "" }, { "docid": "4147049", "text": "Major General Orlando Ward (November 4, 1891 – February 4, 1972) was a career United States Army officer who fought in both World War I and World War II. During the latter, as a major general, he commanded the 1st Armored Division during Operation Torch and during the first few months of the Tunisia Campaign, before being relieved in March 1943. He trained and returned to Europe in 1945 as commander of the 20th Armored Division.", "title": "" }, { "docid": "1458982", "text": "The Norwegian Campaign, lasting from 9 April to 10 June 1940, led to the first direct land confrontation between the military forces of the Allies — United Kingdom and France — against Nazi Germany in World War II.", "title": "" }, { "docid": "37635762", "text": "The 1940 Mitropa Cup was the 14th edition of the Mitropa Cup and the last season played before the competition was interrupted by the Second World War. The competition would be resumed after the war under the name \"Zentropa Cup\" but by that time it was overshadowed by the newly formed European Cup which included teams from all parts of Europe. Last season's champions Újpest FC were eliminated at the quarter-final stage of the competition. This edition is notable for being the first edition in which a team from Romania reached the final. Rapid București of Romania beat Hungária FC MTK Budapest of Hungary in the quarterfinals and got past Građanski Zagreb of Yugoslavia in the semifinals to get to the finals in which they were to play Ferencvárosi FC. The final was cancelled due to the Second World War.", "title": "" }, { "docid": "1192390", "text": "This table compares tanks in use by the belligerent nations of Europe and the Pacific at the start of the Second World War, employed in the Polish Campaign (1939), the Battle of France (1940), Operation Barbarossa (1941), and the Malayan Campaign (1942).", "title": "" }, { "docid": "13788091", "text": "The Royal Naval Commandos were a commando formation of the Royal Navy which served during the Second World War. The first units were raised in 1942 and by the end of the war, 22 company-sized units had been raised to carry out various tasks associated with establishing, maintaining and controlling beachheads during amphibious operations. Royal Naval Commando parties took part in all Allied amphibious landings from early 1942 to the end of the war, when they were disbanded. Operations included the landings at Diego Suarez on Madagascar, Operation Torch, Operation Neptune, the Screwdriver operations in Burma, Operation Market-Garden and the assault on Walcheren.", "title": "" }, { "docid": "5880681", "text": "The Italy Star is a military campaign medal, instituted by the United Kingdom in May 1945 for award to subjects of the British Commonwealth who served in the Second World War, specifically in the Italian Campaign from 1943 to 1945.", "title": "" } ]
647	Integrated care is ineffective at tackling multiple comorbidities.	[ { "docid": "15041758", "text": "OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people SETTING Fourteen primary care clinics in Seattle, Washington. PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10. INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a \"treat to target\" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10). CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. Trial registration Clinical Trials NCT00468676.", "title": "Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial" } ]	[ { "docid": "19945096", "text": "OBJECTIVES To describe and explain the primary care experiences of people with multiple long-term conditions in England. DESIGN AND METHODS Using questionnaire data from 906,578 responders to the English 2012 General Practice Patient Survey, we describe the primary care experiences of patients with long-term conditions, including 583,143 patients who reported one or more long-term conditions. We employed mixed effect logistic regressions to analyse data on six items covering three care domains (access, continuity and communication) and a single item on overall primary care experience. We controlled for sociodemographic characteristics, and for general practice using a random effect, and further, controlled for, and explored the importance of, health-related quality of life measured using the EuroQoL (EQ-5D) scale. RESULTS Most patients with long-term conditions report a positive experience of care at their general practice (after adjusting for sociodemographic characteristics and general practice, range 74.0-93.1% reporting positive experience of care across seven questions) with only modest variation by type of condition. For all three domains of patient experience, an increasing number of comorbid conditions is associated with a reducing percentage of patients reporting a positive experience of care. For example, compared with respondents with no long-term condition, the OR for reporting a positive experience is 0.83 (95% CI 0.80 to 0.87) for respondents with four or more long-term conditions. However, this relationship is no longer observed after adjusting for health-related quality of life (OR (95% CI) single condition=1.23 (1.21 to 1.26); four or more conditions=1.31 (1.25 to 1.37)), with pain making the greatest difference among five quality of life variables included in the analysis. CONCLUSIONS Patients with multiple long-term conditions more frequently report worse experiences in primary care. However, patient-centred measures of health-related quality of life, especially pain, are more important than the number of conditions in explaining why patients with multiple long-term conditions report worse experiences of care.", "title": "Why do patients with multimorbidity in England report worse experiences in primary care? Evidence from the General Practice Patient Survey" }, { "docid": "6767133", "text": "STUDY DESIGN Prospective observational cohort. OBJECTIVE To describe the baseline characteristics of patients with a diagnosis of intervertebral disc herniation who had different treatment preferences and the relationship of specific expectations with those preferences. SUMMARY OF BACKGROUND DATA Data were gathered from the observational cohort of the Spine Patient Outcomes Research Trial (SPORT). Patients in the observational cohort met eligibility requirements identical to those of the randomized cohort, but declined randomization, receiving instead the treatment of their choice. METHODS Baseline preference and expectation data were acquired at the time of enrollment of the patient, before exposure to the informed consent process. Univariate analyses were performed using a t test for continuous variables and chi for categorical variables. Multivariate analyses were also performed with ANCOVA for continuous variables and logistic regression for categorical variables. Multiple logistic regression models were developed in a forward stepwise fashion using blocks of variables. RESULTS More patients preferred operative care: 67% preferred surgery, 28% preferred nonoperative treatment, and 6% were unsure; 53% of those preferring surgery stated a definite preference, whereas only 18% of those preferring nonoperative care had a definite preference. Patients preferring surgery were younger, had lower levels of education, and higher levels of unemployment/disability. This group also reported higher pain, worse physical and mental functioning, more back pain related disability, a longer duration of symptoms, and more opiate use. Gender, race, comorbidities, and use of other therapies did not differ significantly across preference groups. Patients' expectations regarding improvement with nonoperative care was the strongest predictor of preference. CONCLUSION Patient expectations, particularly regarding the benefit of nonoperative treatment, are the primary determinant of surgery preference among patients with lumbar intervertebral disc herniation. Demographic, functional status, and prior treatment experience had significant associations with patients' expectations and preferences.", "title": "Patient preferences and expectations for care: determinants in patients with lumbar intervertebral disc herniation." }, { "docid": "44409062", "text": "In recent years, a new paradigm for genome annotation has emerged, termed \"proteogenomics,\" that leverages peptide MS to annotate a genome. This is achieved by mapping peptides to a six-frame translation of a genome, including available splice databases, which may suggest refinements to gene models. Using this approach, it is possible to refine gene regions such as exon boundaries, novel genes, gene boundaries, frame shifts, reverse strands, translated UTRs, and novel splice junctions. One of the challenges of proteogenomics is how best to (1) tackle assigning confidence to any resulting annotation and (2) apply these gene model refinements, either through manual annotation or through an automated process via training gene prediction tools. This is not a straightforward process, as many gene prediction tools have their defined suitability for niche genomes (either eukaryotic or prokaryotic) trained on and refined with model organisms such as Arabidopsis thaliana and Escherichia coli, and varying degrees of features that can leverage the use of external evidence. In this study, we outline a suitable approach toward preprocessing mass spectra and optimizing the MS/MS search for a given dataset. We also discuss future challenges, which continue to pose a problem in the field of proteogenomics, and better strategies to successfully tackle them with, using existing tools. We use Bradyrhizobium diazoefficiens (Nitrogen-fixing bacteria), with a 9.1 Mb genome as a case study, utilizing the latest in second-generation proteogenomics tools with multiple gene models for cross-validation of proteogenomics annotations.", "title": "High-throughput parallel proteogenomics: a bacterial case study." }, { "docid": "6334188", "text": "BACKGROUND Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.", "title": "History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis." }, { "docid": "7595742", "text": "Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.", "title": "Frailty Syndrome: A Transitional State in a Dynamic Process" }, { "docid": "5836", "text": "Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.", "title": "Induction of myelodysplasia by myeloid-derived suppressor cells." }, { "docid": "9274291", "text": "PURPOSE To compare expectations for cancer survivorship care between patients and their physicians and between primary care providers (PCPs) and oncologists. METHODS Survivors and their physicians were surveyed to evaluate for expectations regarding physician participation in primary cancer follow-up, screening for other cancers, general preventive health, and management of comorbidities. RESULTS Of 992 eligible survivors and 607 physicians surveyed, 535 (54%) and 378 (62%) were assessable, respectively. Among physician respondents, 255 (67%) were PCPs and 123 (33%) were oncologists. Comparing patients with their oncologists, expectations were highly discrepant for screening for cancers other than the index one (agreement rate, 29%), with patients anticipating significantly more oncologist involvement. Between patients and their PCPs, expectations were most incongruent for primary cancer follow-up (agreement rate, 35%), with PCPs indicating they should contribute a much greater part to this aspect of care. Expectations between patients and their PCPs were generally more concordant than between patients and their oncologists. PCPs and oncologists showed high discordances in perceptions of their own roles for primary cancer follow-up, cancer screening, and general preventive health (agreement rates of 3%, 44%, and 51%, respectively). In the case of primary cancer follow-up, both PCPs and oncologists indicated they should carry substantial responsibility for this task. CONCLUSION Patients and physicians have discordant expectations with respect to the roles of PCPs and oncologists in cancer survivorship care. Uncertainties around physician roles and responsibilities can lead to deficiencies in care, supporting the need to make survivorship care planning a standard component in cancer management.", "title": "Comparisons of patient and physician expectations for cancer survivorship care." }, { "docid": "46353045", "text": "Late presentation remains a major concern despite the dramatically improved prognosis realized by ART. We define a first presentation for HIV care during the course of HIV infection as 'late' if an AIDS-defining opportunistic disease is apparent, or if CD4+ T-cells are <200/microl. In the Western world, approximately 10 and 30% of HIV-infected individuals still present with CD4+ T-cells <50 and <200/microl, respectively; estimates are substantially higher for developing countries. Diagnosis and treatment of opportunistic diseases and intense supportive in-hospital care take precedence over ART. Benefits of starting ART without delay, that is, when opportunistic diseases are still active, include faster resolution of opportunistic diseases and a decreased risk of recurrence. The downside of starting ART without delay could include toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). Among asymptomatic or oligosymptomatic individuals presenting late, where ART and primary prophylaxis are initiated, approximately 10-20% will become symptomatic from drug toxicity or undiagnosed opportunistic complications, including IRIS, which require appropriate therapies. In this review we describe late presentation to HIV care, the scale of the problem, the evaluation of a late-presenting patient and challenges associated with initiation of potent antiretroviral therapy (ART) in the setting of acute opportunistic infections and other comorbidities.", "title": "Late presentation of HIV-infected individuals." }, { "docid": "24276304", "text": "CONTEXT Uncertainties exist about prevalence and correlates of major depressive disorder (MDD). OBJECTIVE To present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R). DESIGN Face-to-face household survey conducted from February 2001 to December 2002. SETTING The 48 contiguous United States. PARTICIPANTS Household residents ages 18 years or older (N = 9090) who responded to the NCS-R survey. MAIN OUTCOME MEASURES Prevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV. RESULTS The prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence. CONCLUSIONS Major depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.", "title": "The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R)." }, { "docid": "22688699", "text": "OBJECT Awake craniotomy was performed as the standard surgical approach to supratentorial intraaxial tumors, regardless of the involvement of eloquent cortex, in a prospective trial of 200 patients surgically treated by the same surgeon at a single institution. METHODS Patient presentations, comorbid conditions, tumor locations, and the histological characteristics of lesions were recorded. Brain mapping was possible in 195 (97.5%) of 200 patients. The total number of patients sustaining complications was 33 for an overall complication rate of 16.5%. There were two deaths in this series, for a mortality rate of 1%. New postoperative neurological deficits were seen in 13% of the patients, but these were permanent in only 4.5% of them. Complication rates were higher in patients who had gliomas or preoperative neurological deficits and in those who had undergone prior radiation therapy or surgery. No patient who entered the operating room neurologically intact sustained a permanent neurological deficit postoperatively. Of the most recent 50 patients treated, three (6%) required a stay in the intensive care unit, and the median total hospital stay was 1 day. CONCLUSIONS Use of awake craniotomy can result in a considerable reduction in resource utilization without compromising patient care by minimizing intensive care time and total hospital stay. Awake craniotomy is a practical and effective standard surgical approach to supratentorial tumors with a low complication rate, and provides an excellent alternative to craniotomy performed with the patient in the state of general anesthesia because it allows the opportunity for brain mapping and avoids general anesthesia.", "title": "Awake craniotomy with brain mapping as the routine surgical approach to treating patients with supratentorial intraaxial tumors: a prospective trial of 200 cases." }, { "docid": "24318630", "text": "Since 2008 the World Health Organization (WHO), through its mental health Gap Action Programme, has attempted to revitalize efforts to integrate mental health into non-specialized (e.g. primary) healthcare. While this has led to renewed interest in this potential method of mental health service delivery, it has also prompted criticism. Some concerns raised are that it would contribute to the medicalization of social and psychological problems, and narrowly focus on primary care without sufficient attention given to strengthening other levels of the healthcare system, notably community-based care and care on district levels. This paper discusses seven elements that may be critical to preventing inadvertently contributing to increasing a narrow biomedical approach to mental healthcare when integrating mental health into non-specialized healthcare: (1) using task shifting approaches within a system of stepped care, (2) ensuring primary mental healthcare also includes brief psychotherapeutic interventions, (3) promote community-based recovery-oriented interventions for people with disabling chronic mental disorders, (4) conceptualizing training as a continuous process of strengthening clinical competencies through supervision, (5) engaging communities as partners in psychosocial interventions, (6) embedding shifts to primary mental healthcare within wider health policy reforms, and (7) promoting inter-sectoral approaches to address social determinants of mental health.", "title": "Integration of mental health into primary healthcare in low-income countries: avoiding medicalization." }, { "docid": "17693849", "text": "BACKGROUND Appropriate understanding of health information by patients with cardiovascular disease (CVD) is fundamental for better management of risk factors and improved morbidity, which can also benefit their quality of life. OBJECTIVES To assess the relationship between health literacy and health-related quality of life (HRQoL) in patients with ischaemic heart disease (IHD), and to investigate the role of sociodemographic and clinical variables as possible confounders. METHODS Cross-sectional study of patients with IHD recruited from a stratified sample of general practices in two Australian states (Queensland and South Australia) between 2007 and 2009. Health literacy was measured using a validated questionnaire and classified as inadequate, marginal, or adequate. Physical and mental components of HRQoL were assessed using the Medical Outcomes Study Short Form (SF12) questionnaire. Analyses were adjusted for confounders (sociodemographic variables, clinical history of IHD, number of CVD comorbidities, and CVD risk factors) using multiple linear regression. RESULTS A total sample of 587 patients with IHD (mean age 72.0±8.4 years) was evaluated: 76.8% males, 84.2% retired or pensioner, and 51.4% with up to secondary educational level. Health literacy showed a mean of 39.6±6.7 points, with 14.3% (95%CI 11.8-17.3) classified as inadequate. Scores of the physical component of HRQoL were 39.6 (95%CI 37.1-42.1), 42.1 (95%CI 40.8-43.3) and 44.8 (95%CI 43.3-46.2) for inadequate, marginal, and adequate health literacy, respectively (p-value for trend = 0.001). This association persisted after adjustment for confounders. Health literacy was not associated with the mental component of HRQoL (p-value = 0.482). Advanced age, lower educational level, disadvantaged socioeconomic position, and a larger number of CVD comorbidities adversely affected both, health literacy and HRQoL. CONCLUSION Inadequate health literacy is a contributing factor to poor physical functioning in patients with IHD. Increasing health literacy may improve HRQoL and reduce the impact of IHD among patients with this chronic CVD.", "title": "Effect of Health Literacy on Quality of Life amongst Patients with Ischaemic Heart Disease in Australian General Practice" }, { "docid": "20187433", "text": "Family members are an integral part of a patient's cancer care from the moment the diagnosis is delivered to the conclusion of treatment. Family members bring with them a range of emotional reactions, interpersonal dynamics and expectations for the care the patient receives. This study is part of a multi-institutional project to continue to improve the process of cancer care. In this study, 19 focus groups (11 patient and 8 provider) were conducted concerning issues related to doctor-patient communication in eight cancer centers in the United States. The content of the conversations was analyzed and thematic categories emerged that highlight the various strengths and difficulties associated with family involvement. The focus groups' comments support the need for explicit conversations between professional caregivers, patients and their loved ones, in order to negotiate the expectations and needs of each team member. Implications for clinical practice and strategies for working with family members are offered.", "title": "Involving family members in cancer care: focus group considerations of patients and oncological providers." }, { "docid": "6517267", "text": "BACKGROUND The Dutch multidisciplinary sciatica guideline recommends that the team of professionals involved in sciatica care and the patient together decide on surgical or prolonged conservative treatment (shared decision making [SDM]). Despite this recommendation, SDM is not yet integrated in sciatica care. Existing literature concerning barriers and facilitators to SDM implementation mainly focuses on one discipline only, whereas multidisciplinary care may involve other barriers and facilitators, or make these more complex for both professionals and patients. Therefore, this qualitative study aims to identify barriers and facilitators perceived by patients and professionals for SDM implementation in multidisciplinary sciatica care. METHODS We conducted 40 semi-structured interviews with professionals involved in sciatica care (general practitioners, physical therapists, neurologists, neurosurgeons, and orthopedic surgeons) and three focus groups among patients (six to eight per group). The interviews and focus groups were audiotaped and transcribed in full. Reported barriers and facilitators were classified according to the framework of Grol and Wensing. The software package Atlas.ti 7.0 was used for analysis. RESULTS Professionals reported 53 barriers and 5 facilitators, and patients 35 barriers and 18 facilitators for SDM in sciatica care. Professionals perceived most barriers at the level of the organizational context, and facilitators at the level of the individual professional. Patients reported most barriers and facilitators at the level of the individual professional. Several barriers and facilitators correspond with barriers and facilitators found in the literature (e.g., lack of time, motivation) but also new barriers and facilitators were identified. Many of these new barriers mentioned by both professionals and patients were related to the multidisciplinary setting, such as lack of visibility, lack of trust in expertise of other disciplines, and lack of communication between disciplines. CONCLUSIONS This study identified barriers and facilitators for SDM in the multidisciplinary sciatica setting, by both professionals and patients. It is clear that more barriers than facilitators are perceived for implementation of SDM in sciatica care. Newly identified barriers and facilitators are related to the multidisciplinary care setting. Therefore, an effective implementation strategy of SDM in a multidisciplinary setting such as in sciatica care should focus on these barriers and facilitators.", "title": "Barriers and facilitators to implement shared decision making in multidisciplinary sciatica care: a qualitative study" }, { "docid": "44830890", "text": "OBJECTIVE To investigate the frequency of depressive and anxiety disorders in patients with chronic daily headache. BACKGROUND There is a lack of data in the literature on the extent of psychiatric comorbidity in patients with different subtypes of chronic daily headache. METHODS We recruited consecutive patients with chronic daily headache seen in a headache clinic from November 1998 to December 1999. The subtypes of chronic daily headache were classified according to the criteria proposed by Silberstein et al. A psychiatrist evaluated the patients according to the structured Mini-International Neuropsychiatric Interview to assess the comorbidity of depressive and anxiety disorders. RESULTS Two hundred sixty-one patients with chronic daily headache were recruited. The mean age was 46 years, and 80% were women. Transformed migraine was diagnosed in 152 patients (58%) and chronic tension-type headache in 92 patients (35%). Seventy-eight percent of patients with transformed migraine had psychiatric comorbidity, including major depression (57%), dysthymia (11%), panic disorder (30%), and generalized anxiety disorder (8%). Sixty-four percent of patients with chronic tension-type headache had psychiatric diagnoses, including major depression (51%), dysthymia (8%), panic disorder (22%), and generalized anxiety disorder (1%). The frequency of anxiety disorders was significantly higher in patients with transformed migraine after controlling for age and sex (P =.02). Both depressive and anxiety disorders were significantly more frequent in women. CONCLUSION Psychiatric comorbidity, especially major depression and panic disorders, was highly prevalent in patients with chronic daily headache seen in a headache clinic. These results demonstrate that women and patients with transformed migraine are at higher risk of psychiatric comorbidity.", "title": "Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes." }, { "docid": "15968271", "text": "OBJECTIVE Our objective is to estimate and compare the prevalence of selected adverse consequences associated with unmet need for assistance among a socioeconomically and medically vulnerable subgroup of the older adult population, those who are dually eligible for Medicare and Medicaid, with those eligible for Medicare only. METHOD Using data from the National Health and Aging Trends Study (NHATS), a representative survey of the older Medicare population, we calculated the prevalence of disability-related need for assistance with self-care, household tasks, and mobility activities and the prevalence of adverse consequences of unmet need by dually eligible and Medicare only status. RESULTS Over 2 million community-dwelling older persons experienced an adverse consequence due to unmet need for assistance with self-care (e.g., soiled their clothes), over 2 million experienced adverse consequences due to unmet need for assistance with household tasks (e.g., went without groceries), and over 3 million persons experienced at least one adverse consequence of unmet need for assistance with mobility-related activities (e.g., had to stay in bed) in the month prior to the NHATS interview. Dually eligible persons experienced higher rates of 6 of the 11 adverse consequences studied and were more likely to have at least one adverse consequence in all 3 domains than others. DISCUSSION Several care models are emerging with the goal of integrating medical care, behavioral health, and long-term services for the dual eligible population. Indicators of adverse consequences of unmet need could be used to monitor the quality and adequacy of such care systems.", "title": "The adverse consequences of unmet need among older persons living in the community: dual-eligible versus Medicare-only beneficiaries." }, { "docid": "474325", "text": "The helmet is a new interface with the potential of increasing the success rate of non-invasive ventilation by improving tolerance. To perform a physiological comparison between the helmet and the conventional facial mask in delivering non-invasive ventilation in hypercapnic patients with chronic obstructive pulmonary disease. Prospective, controlled, randomized study with cross-over design. In 10 patients we evaluated gas exchange, inspiratory effort, patient–ventilator synchrony and patient tolerance after 30 min of non-invasive ventilation delivered either by helmet or facial mask; both trials were preceded by periods of spontaneous unassisted breathing. Arterial blood gases, inspiratory effort, duration of diaphragm contraction and ventilator assistance, effort-to-support delays (at the beginning and at the end of inspiration), number of ineffective efforts, and patient comfort. Non-invasive ventilation improved gas exchange (p< 0.05) and inspiratory effort (p< 0.01) with both interfaces. The helmet, however, was less efficient than the mask in reducing inspiratory effort (p< 0.05) and worsened the patient–ventilator synchrony, as indicated by the longer delays to trigger on (p< 0.05) and cycle off (p< 0.05) the mechanical assistance and by the number of ineffective efforts (p< 0.005). Patient comfort was no different with the two interfaces. Helmet and facial mask were equally tolerated and both were effective in ameliorating gas exchange and decreasing inspiratory effort. The helmet, however, was less efficient in decreasing inspiratory effort and worsened the patient–ventilator interaction.", "title": "Non-invasive ventilation in chronic obstructive pulmonary disease patients: helmet versus facial mask" }, { "docid": "42095718", "text": "Clinical evidence suggests that chronic daily headache (CDH) occurs in association with psychopathologies: previous studies have focused particularly on migraine. To evaluate this association, we studied, using the DSM-IIIR criteria, a population of 88 patients (18M, 70F) affected by CDH (mean duration 7.4 +/- 8.7 years). We documented the presence of a psychiatric disorder in 90% of this population. The most frequent diagnosis was a comorbidity of anxiety and mood disorders. The comorbidity of psychiatric disorders and headache has important implications as far as treatment is concerned.", "title": "Psychiatric comorbidity in chronic daily headache." }, { "docid": "20109325", "text": "Chronic obstructive pulmonary disease (COPD) is a global health problem, and since 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents the main contents of the second 5-year revision of the GOLD document that has implemented some of the vast knowledge about COPD accumulated over the last years. Today, GOLD recommends that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation. The document highlights that the assessment of the patient with COPD should always include assessment of (1) symptoms, (2) severity of airflow limitation, (3) history of exacerbations, and (4) comorbidities. The first three points can be used to evaluate level of symptoms and risk of future exacerbations, and this is done in a way that splits patients with COPD into four categories-A, B, C, and D. Nonpharmacologic and pharmacologic management of COPD match this assessment in an evidence-based attempt to relieve symptoms and reduce risk of exacerbations. Identification and treatment of comorbidities must have high priority, and a separate section in the document addresses management of comorbidities as well as COPD in the presence of comorbidities. The revised document also contains a new section on exacerbations of COPD. The GOLD initiative will continue to bring COPD to the attention of all relevant shareholders and will hopefully inspire future national and local guidelines on the management of COPD.", "title": "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary." }, { "docid": "6171953", "text": "Inflammation accompanies obesity and its comorbidities-type 2 diabetes, non-alcoholic fatty liver disease and atherosclerosis, among others-and may contribute to their pathogenesis. Yet the cellular machinery that links nutrient sensing to inflammation remains incompletely characterized. The protein deacetylase sirtuin-1 (SirT1) is activated by energy depletion and plays a critical role in the mammalian response to fasting. More recently it has been implicated in the repression of inflammation. SirT1 mRNA and protein expression are suppressed in obese rodent and human white adipose tissue, while experimental reduction of SirT1 in adipocytes and macrophages causes low-grade inflammation that mimics that observed in obesity. Thus suppression of SirT1 during overnutrition may be critical to the development of obesity-associated inflammation. This effect is attributable to multiple actions of SirT1, including direct deacetylation of NFκB and chromatin remodeling at inflammatory gene promoters. In this work, we report that SirT1 is also suppressed by diet-induced obesity in macrophages, which are key contributors to the ontogeny of metabolic inflammation. Thus, SirT1 may be a common mechanism by which cells sense nutrient status and modulate inflammatory signaling networks in accordance with organismal energy availability.", "title": "Sirtuin-1 is a nutrient-dependent modulator of inflammation" }, { "docid": "13906581", "text": "Background Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones. Thus, our goal was to systematically evaluate the evidence pertaining to this question. Methods and Findings We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition. Studies were retrieved from PubMed, contact with experts, and literature cross-referencing. Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome. Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both). Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones. There was considerable heterogeneity between studies (I2 = 72% for the main analysis). Results were similar in studies using clinical and those using administrative databases. No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01). Smaller studies did not differ in their results from larger studies. Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude. Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones. Conclusions The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes. Differences for specific diseases cannot be excluded, but are likely to be small.", "title": "Patient Outcomes with Teaching Versus Nonteaching Healthcare: A Systematic Review" }, { "docid": "2048139", "text": "BackgroundIndividuals with substance use disorders (SUDs) are at increased risk for hepatitis C viral infection (HCV), and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN) completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare Administration (VHA) between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN) or combination therapy (IFN and ribavirin) who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group) and patients without a history of SUD (SUD- Group).ResultsOdds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4 (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%) and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%).ConclusionIndividuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.", "title": "Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders" }, { "docid": "45457778", "text": "The change in the world's age demographics and the predicted rise in the incidence of age-related diseases, including dementia, is a source of major public health concern. Major research effort in both the United States and Europe has been targeted toward understanding the pathogenesis and epidemiology of dementia. This article presents a general overview of the history of dementia research in Europe and how it compares with that in the United States. The review highlights the common issues which both U.S. and European researchers have identified and attempted to tackle. To maximize information gained from studies across the world, better harmonization of methodology is needed, as informed from current research practice.", "title": "A European perspective on population studies of dementia." }, { "docid": "26067999", "text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l", "title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement" }, { "docid": "13282296", "text": "CONTEXT Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes. OBJECTIVE To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years. DESIGN, SETTING, AND PATIENTS A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California. MAIN OUTCOME MEASURE Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease. RESULTS At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55). CONCLUSIONS Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.", "title": "Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus." }, { "docid": "25837950", "text": "Obesity is associated with higher mortality in the general population, but this association is reversed in patients on dialysis. The nature of the relationship of obesity with adverse clinical outcomes in nondialysis-dependent CKD and the putative interaction of the severity of disease with this association are unclear. We analyzed data from a nationally representative cohort of 453,946 United States veterans with eGFR<60 ml/min per 1.73 m(2). The associations of body mass index categories (<20, 20 to <25, 25 to <30, 30 to <35, 35 to <40, 40 to <45, 45 to <50, and ≥50 kg/m(2)) with all-cause mortality and disease progression (using multiple definitions, including incidence of ESRD, doubling of serum creatinine, and the slopes of eGFR) were examined in Cox proportional hazards models and logistic regression models. Multivariable adjustments were made for age, race, comorbidities and medications, and baseline eGFR. Body mass index showed a relatively consistent U-shaped association with clinical outcomes, with the best outcomes observed in overweight and mildly obese patients. Body mass index levels <25 kg/m(2) were associated with worse outcomes in all patients, independent of severity of CKD. Body mass index levels ≥35 kg/m(2) were associated with worse outcomes in patients with earlier stages of CKD, but this association was attenuated in those patients with eGFR<30 ml/min per 1.73 m(2). Thus, until clinical trials establish the ideal body mass index, a cautious approach to weight management is warranted in this patient population.", "title": "Association of body mass index with outcomes in patients with CKD." }, { "docid": "24323695", "text": "RATIONALE Up to 80% of patients with lung cancer have comorbid chronic obstructive pulmonary disease (COPD). Many of them are poor candidates for stage-specific lung cancer treatment due to diminished lung function and poor functional status, and many forego treatment. The negative effect of COPD may be moderated by pulmonologist-guided management. OBJECTIVES This study examined the association between pulmonologist management and the probability of receiving the recommended stage-specific treatment modality and overall survival among patients with non-small cell lung cancer (NSCLC) with preexisting COPD. METHODS Early- and advanced-stage NSCLC cases diagnosed between 2002 and 2005 with a prior COPD diagnosis (3-24 months before NSCLC diagnosis) were identified in Surveillance, Epidemiology, and End Results tumor registry data linked to Medicare claims. Study outcomes included receipt of recommended stage-specific treatment (surgical resection for early-stage NSCLC and chemotherapy for advanced-stage NSCLC [advNSCLC]) and overall survival. Pulmonologist management was considered present if one or more Evaluation and Management visit claims with pulmonologist specialty were observed within 6 months after NSCLC diagnosis. Stage-specific multivariate logistic regression tested association between pulmonologist management and treatment received. Cox proportional hazard models examined the independent association between pulmonologist care and mortality. Two-stage residual inclusion instrumental variable (2SRI-IV) analyses tested and adjusted for potential confounding based on unobserved factors or measurement error. MEASUREMENTS AND MAIN RESULTS The cohorts included 5,488 patients with early-stage NSCLC and 6,426 patients with advNSCLC disease with preexisting COPD. Pulmonologist management was recorded for 54.9% of patients with early stage NSCLC and 35.7% of patients with advNSCLC. Of those patients with pulmonologist involvement, 58.5% of patients with early NSCLC received surgical resection, and 43.6% of patients with advNSCLC received chemotherapy. Pulmonologist management post NSCLC diagnosis was associated with increased surgical resection rates (odds ratio, 1.26; 95% confidence interval, 1.11-1.45) for early NSCLC and increased chemotherapy rates (odds ratio, 1.88; 95% confidence interval, 1.67-2.10) for advNSCLC. Pulmonologist management was also associated with reduced mortality risk for patients with early-stage NSCLC but not AdvNSCLC. CONCLUSIONS Pulmonologist management had a positive association with rates of stage-specific treatment in both groups and overall survival in early-stage NSCLC. These results provide preliminary support for the recently published guidelines emphasizing the role of pulmonologists in lung cancer management.", "title": "Pulmonologist involvement, stage-specific treatment, and survival in adults with non-small cell lung cancer and chronic obstructive pulmonary disease." }, { "docid": "21274919", "text": "OBJECTIVE Chronic physical comorbidity is common in dementia. However, there is an absence of evidence to support good practice guidelines for attention to these problems. We aimed to study the extent of this comorbidity and its impact on cognitive function and disability in population-based studies in low and middle income countries, where chronic diseases and impairments are likely to be both common and undertreated. METHODS A multicentre cross-sectional survey of all over 65 year old residents (n = 15 022) in 11 catchment areas in China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru. We estimated the prevalence of pain, incontinence, hearing and visual impairments, mobility impairment and undernutrition according to the presence of dementia and its severity, and, among those with dementia, the independent contribution of these impairments to cognitive function and disability, adjusting for age, gender, education and dementia severity. RESULTS Incontinence, hearing impairment, mobility impairment and undernutrition were consistently linearly associated with the presence of dementia and its severity across regions. Among people with dementia, incontinence, hearing impairment and mobility impairment were independently associated with disability in all regions while the contributions of pain, visual impairment and undernutrition were inconsistent. Only hearing impairment made a notable independent contribution to cognitive impairment. CONCLUSIONS There is an urgent need for clinical trials of the feasibility, efficacy and cost-effectiveness of regular physical health checks and remediation of identified pathologies, given the considerable comorbidity identified in our population based studies, and the strong evidence for independent impact upon functioning.", "title": "The association between common physical impairments and dementia in low and middle income countries, and, among people with dementia, their association with cognitive function and disability. A 10/66 Dementia Research Group population-based study." }, { "docid": "1412089", "text": "BACKGROUND Traditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging provides a unique opportunity to investigate the extent and nature of structural injury, but has been limited by examining only a subset of regions of interest (ROI) and by confounds common to the study of an elderly population, including comorbid vascular pathology. Furthermore, comprehensive correlation of diffusion tensor imaging (DTI) measurements, including axial and radial diffusivity measurements, has not been demonstrated in the late life depression population. METHODS 51 depressed and 16 non-depressed, age- and cerebrovascular risk factor-matched elderly subjects underwent traditional anatomic T1 and T2 weight imaging, as well as DTI. The DTI data were skeletonized using tract based spatial statistics (TBSS), and both regional and global analyses were performed. RESULTS Widespread structural abnormalities within white matter were detected in the LLD group, accounting for age, gender and education and matched for cerebrovascular risk factors and global T2 white matter hyperintensities (T2WMH). Regional differences were most prominent in uncinate and cingulate white matter and were generally characterized by an increase in radial diffusivity. Age-related changes particularly in the cingulate bundle were more advanced in individuals with LLD relative to controls. Regression analysis demonstrated significant correlations of regional fractional anisotropy and radial diffusivity with five different neuropsychological factor scores. TBSS analysis demonstrated a greater extent of white matter abnormalities in LLD not responsive to treatment, as compared to controls. CONCLUSIONS White matter integrity is compromised in late life depression, largely manifested by increased radial diffusivity in specific regions, suggesting underlying myelin injury. A possible mechanism for underlying myelin injury is chronic white matter ischemia related to intrinsic cerebrovascular disease. In some regions such as the cingulate bundle, the white matter injury related to late life depression appears to be independent of and compounded by age-related changes. The correlations with neuropsychological testing indicate the essential effects of white matter injury on functional status. Lastly, response to treatment may depend on the extent of white matter injury, suggesting a need for intact functional networks.", "title": "Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities." }, { "docid": "32777637", "text": "BACKGROUND Concurrent use of multiple standing antipsychotics (antipsychotic polypharmacy) is increasingly common among both inpatients and outpatients. Although this has often been cited as a potential quality-of-care problem, reviews of research evidence on antipsychotic polypharmacy have not distinguished between appropriate versus inappropriate use. METHODS A MEDLINE search from 1966 to December 2007 was completed to identify studies comparing changes in symptoms, functioning, and/or side effects between patients treated with multiple antipsychotics and patients treated with a single antipsychotic. The studies were reviewed in two groups on the basis of whether prescribing was concordant with guideline recommendations for multiple-antipsychotic use. RESULTS A review of the literature, including three randomized controlled trials, found no support for the use of antipsychotic polypharmacy in patients without an established history of treatment resistance to multiple trials of monotherapy. In patients with a history of treatment resistance to multiple monotherapy trials, limited data support antipsychotic polypharmacy, but positive outcomes were primarily found in studies of clozapine augmented with a second-generation antipsychotic. DISCUSSION Research evidence is consistent with the goal of avoiding antipsychotic polypharmacy in patients who lack guideline-recommended indications for its use. The Joint Commission is implementing a core measure set for Hospital-Based Inpatient Psychiatric Services. Two of the measures address antipsychotic polypharmacy. The first measure assesses the overall rate. The second measure determines whether clinically appropriate justification has been documented supporting the use of more than one antipsychotic medication.", "title": "When is antipsychotic polypharmacy supported by research evidence? Implications for QI." } ]
5a8f6471554299458435d609	The reality/comedy tv series Monster House was hosted by which Sydney-based Australian actor?	[ { "docid": "14068698", "text": "Bernard Curry (born 27 March 1974) is a Sydney-based Australian actor, best known for his role in soap operas as Luke Handley in \"Neighbours\" and Hugo Austin in \"Home and Away\". He is currently appearing as Jake Stewart in the prison-drama series \"Wentworth\".", "title": "" }, { "docid": "15192613", "text": "Monster House was an Australian reality/comedy television series broadcast on the Nine Network. Debuting on 12 February 2008, the program was hosted by Bernard Curry, brother of Stephen and Andrew Curry.", "title": "" } ]	[ { "docid": "17964483", "text": "Simon Dodd (born 7 June 1959) is an Australian comedy writer, author, playwright and feature writer. He is the recipient of ten Australian Writers' Guild AWGIE Awards as part of the writing team behind such successful TV series as \"Good News Week\" and \"The Glass House\". His list of credits includes popular Australian comedy TV shows from the late 1980s until today. He also wrote for Logies host Andrew Denton in 1999 and 2000. In 2014, he produced and directed his Absurdist comedy stage-play \"Plaything\" at the Factory Theatre for the Sydney Comedy Festival, garnering a number of positive reviews.", "title": "" }, { "docid": "44144844", "text": "The Amazing Race 1 () is a Chinese reality television series loosely based on the American reality TV series, \"The Amazing Race\". It is the first season of The Amazing Race (). It features eight teams of two in a race around the world. This is the second version of \"The Amazing Race\" to be produced in China, following \"\". This new version is broadcast on Shenzhen TV, and had its premiere on October 17, 2014. The hosts for the show are Hong Kong actor Andy On and Singapore based Chinese-American actor Allan Wu, who was also the host of \"The Amazing Race Asia\" and \"The Amazing Race: China Rush\".", "title": "" }, { "docid": "4171252", "text": "Ajay Rochester (born in 1969 in Sydney) is an Australian actress and author. She was the host of the Australian version of reality weight-loss television series \"The Biggest Loser\", for which she hosted a total of four series between 2006 and 2009.", "title": "" }, { "docid": "16058532", "text": "John Barbour (born on April 24, 1933 in Toronto, Ontario), known as the godfather of reality TV, is an actor, comedian, television host, and is the only performer in TV to win Emmys for both entertainment and news shows. Barbour is known as one of the hosts of the NBC reality television series \"Real People\", for which he was also a creator and co-producer.", "title": "" }, { "docid": "26716674", "text": "This Is Your Life is an Australian television documentary and reality show, based on the American show of the same name, in which the host surprises guests with a show documenting their lives, with audience participation from their friends and family.", "title": "" }, { "docid": "21881630", "text": "The Chopping Block is an American reality television series, based on the Australian reality television series of the same name. The series aired on the NBC network and followed participants in an attempt to open a restaurant. It is hosted by British celebrity chef Marco Pierre White.", "title": "" }, { "docid": "17906377", "text": "Make Me a Supermodel is an Australian reality television series that is based from the successful British TV series of the same title except that men are also allowed to apply. It debuted on the Seven Network on 6 August 2008. It is hosted by the former Miss Universe winner Jennifer Hawkins.", "title": "" }, { "docid": "32645124", "text": "Balls of Steel Australia is an Australian reality comedy television series (based upon the UK series of the same name) which is hosted by The Chaser's Craig Reucassel. The show revolves around comedians who appear and present individual skits where they would perform stunts and hold their nerve during hidden camera set-ups in the presence of the Australian public.", "title": "" }, { "docid": "14857363", "text": "Outback House was an Australian historical reality TV series that originally aired on ABC TV in 2005. The series was based on several series produced by Channel 4 in the United Kingdom and PBS in the United States, in which the concept was to have a modern-day family living in a facsimile of an historical dwelling with their staff, making do with only the technology and materials of the time. \"Outback House\" was set in 1861 Outback Australia, on a sheep station called Oxley Downs in New South Wales.", "title": "" }, { "docid": "53681195", "text": "Little Big Shots is an Australian reality television show which premiered on the Seven Network on 27 August 2017. The program, based on the American format of the same name, is hosted by Shane Jacobson and features performances by children aged 3 to 13 years old.", "title": "" }, { "docid": "23634016", "text": "TV Burp was an Australian television comedy program which premiered on the Seven Network on 23 July 2009 hosted by Ed Kavalee.", "title": "" }, { "docid": "43720251", "text": "Room for Two is an Australian television series which aired on Sydney station ATN-7 during 1958-1959. Hosted by Ray Taylor, it was an hour-long variety program, and a spin-off from \"Sydney Tonight\". An episode aired 11 December 1958 was the first Australian TV episode to feature songs from the hit musical \"My Fair Lady\". Like many ATN series of the era, the series featured the ATN Orchestra, conducted by Thomas Tycho.", "title": "" }, { "docid": "38483107", "text": "House Rules is an Australian reality television series broadcast on the Seven Network. The series follows six state-based couples who renovate each other's homes to receive the highest scores with the winner to win an ultimate prize.", "title": "" }, { "docid": "43805381", "text": "Curtain Call is an Australian variety series which aired in Sydney on ATN-7 during 1960, which featured comedy and music. It was followed-up in 1961 with the popular \"Revue '61\".", "title": "" }, { "docid": "43929177", "text": "Time Out is an Australian television series which aired 1963 on Sydney station ATN-7. The 10-minute series aired after the ATN-7 evening news (which aired in a 20-minute time-slot), and consisted of TV and stage actors portraying Australian historical figures, who were \"interviewed\" by a faux-interviewer played by actor Alistair Duncan. 26 episodes were produced.", "title": "" }, { "docid": "39940555", "text": "Town Talk, originally \"T.V. Town Talk\", was an Australian television series which aired on Sydney station TCN-9 during 1957, from circa May to December. Little information is available on this series. The series was hosted by early Australian television personality Robert Kennedy, who had been the original host of the Sydney version of \"What's My Line\". \"Town Talk\" aired at 7:15PM on Fridays, following the evening news, which itself aired in a 15-minute time-slot during 1957.", "title": "" }, { "docid": "55351449", "text": "Yes or No (Tamil: யெஸ் ஆர் நோ ) is an 2017 Indian Tamil language reality talent game show which airs on Star Vijay on every Saturday evening from 23 September 2017. The show is hosted by Tamil film Comedy actor Jagan. The game consists of two team celebrities competing with 128 people to win a cash prize.", "title": "" }, { "docid": "35453454", "text": "Monster Man is a reality TV series shown on Syfy.", "title": "" }, { "docid": "43866140", "text": "Startime is an Australian television series which aired 1962 to 1963. A Sydney-produced variety series with emphasis on music, it was hosted by John Laws and produced by ATN-7, with the series shown interstate (such as on HSV-7 in Melbourne). In Sydney it aired each Saturday at 7:30PM. It was produced by American Gil Rodin, and was seen as a follow-up to the \"Revue '62\" series.", "title": "" }, { "docid": "52239596", "text": "This Time Next Year is an Australian reality television show based on the British show of the same name, hosted by Karl Stefanovic, premiered on 31 July 2017.", "title": "" }, { "docid": "32385303", "text": "The Voice is an Australian reality talent show, based on the original Dutch version of the program created by John de Mol and is part of a wider international franchise. The show is hosted by Sonia Kruger, who debuted as host during the fifth season, following the departure of Darren McMullen.", "title": "" }, { "docid": "44878179", "text": "Talking Point is an Australian television series which aired 1960 to 1962 on Sydney station ATN-7 (Australian TV was not fully networked at the time, and most non-imported series aired on a single station). It was a discussion series featuring a panel of four. Angus Maude was the original host, later it was hosted by Joe Gullett. In one episode, the panel criticised the banning of the book \"Lady Chatterley's Lover\", in another episode there was a debate on the future of the United Nations, while another episode featured a discussion of the space race.", "title": "" }, { "docid": "14312190", "text": "Dirty Jobs was a reality/factual program on the Nine Network, based on the American version of the same name, in which hosts Jo Beth Taylor and Ben Dark are shown performing difficult, strange, and/or messy occupational duties alongside professional workers.", "title": "" }, { "docid": "54374417", "text": "A Casa (English: \"The House\") is a Brazilian reality television game show based on the Dutch television series \"Get The F*ck Out Of My House\", hosted by Marcos Mion. The series premiered Tuesday, June 27, 2017 at 10:30 p.m. on RecordTV.", "title": "" }, { "docid": "45225705", "text": "Room 101 is a SBS One comedy television series hosted by Paul McDermott, based on the UK series of the same name, in which celebrities are invited to discuss their dislikes and pet hates. The series was scheduled to premiere on February 23, 2015 but the network decided to delay the launch until July 11, 2015.", "title": "" }, { "docid": "12286790", "text": "Don was a reality TV series in the form of a documentary that was initially launched for Zee News, but later was aired on Zee TV. It was hosted by Bollywood actor, Irfan Khan.", "title": "" }, { "docid": "42635188", "text": "On Camera is an Australian television which aired 1959–1960 on Sydney station ATN-7. A variety series with music and comedy, regulars included Colin Croft and John Ewart. It was shown twice-monthly. Confusingly, the Canadian series \"On Camera\" had previously been shown on Australian television.", "title": "" }, { "docid": "3078534", "text": "BackBerner was an Australian political satire sketch comedy television series, broadcast on and produced by ABC TV with Crackerjack Productions. The program was hosted by stand up comic Peter Berner and noted Australian character actor Louise Siversen. The series aired from 19 August 1999 to 14 November 2002.", "title": "" }, { "docid": "10201873", "text": "Steve Watson (born June 11, 1972) is an American actor. He is best known for his role as the host of Discovery Channel's reality program \"Monster House\" (2003–2006). He appeared on \"Ice Road Truckers\" during the \"after\" special and currently serves as host of HGTV's \"Don't Sweat It\" (2006–2011).", "title": "" }, { "docid": "37947552", "text": "Splash is an American competition-based reality show with celebrity diving competitions which broadcast on ABC from March 19 to May 7, 2013. It was based on the Dutch reality franchise \"Celebrity Splash!\" created by Eyeworks for the series \"Stars Jumping on Saturday\" (Dutch: \"Sterren Springen Op Zaterdag\" ) that premiered in 2012. The show was hosted by actor Joey Lawrence and sportscaster Charissa Thompson with former Olympic divers Steve Foley from Australia and David Boudia from the U.S. as judges. Greg Louganis, also a former U.S. Olympic diver, was the diving instructor and mentor to the celebrities.", "title": "" } ]
773	Transfering money from NRE account in India to family member	[ { "docid": "157712", "text": "I am a US citizen and I want to transfer some amount 10 lakhs+ to my brother from my NRE account in India to his account. My brother is going to purchase something for his business. He is going to return my amount after 3-4 Months From the description it looks like you would like to loan to your brother on repatriation basis. Yes this is allowed. See the RBI Guide here and here for more details. There are some conditions; (iv) Scheme for raising loans from NRIs on repatriation basis Borrowings not exceeding US$ 2,50,000 or its equivalent in foreign exchange by an individual resident in India from his close relatives resident outside India, subject to the conditions that - a) the loan is free of interest; b) the minimum maturity period of the loan is seven years; c) The amount of loan is received by inward remittance in free foreign exchange through normal banking channels or by debit to the NRE/FCNR account of the non-resident lender; d) The loan is utilised for the borrower's personal purposes or for carrying on his normal business activity but not for carrying on agricultural/plantation activities, purchase of immovable property or shares/debentures/bonds issued by companies in India or for re-lending. Although it is mentioned as Seven years, this is revised to one year. Since he cannot deposit into my NRE account I guess he has to deposit it into my NRO account. A repatriate-able loan as above can be deposited into NRE Account. Is there any illegality here doing such transaction? No. Please ensure proper paper work to show this as loan and document the money trail. Also once I get my money in NRO account do I need to pay taxes in India on the money he deposited? This question does not arise.", "title": "" } ]	[ { "docid": "516260", "text": "I have read from lot of places that transferring funds from NRO to NRE is possible given correct documents are provided. Yes this is correct. The key document 15CB establishes that you have paid taxes that were due before money is transferred from the NRO account to the NRE account and/or are repatriated. Here is what I am simply doing- Steps 3 & 4 more so the step 4 can be seen as new income. So the source of the funds is originally from NRE account. However, the CA feels that since my withdrawal and deposit mechanism in NRO is cash, I might be subject to questioning. Is there any issues in doing the above? The CA is right. The Cash Withdrawal and Cash Deposit has broken the link between the money withdrawn and the money deposited. It could easily be the case that the Cash Withdrawals were spent on expenses and the Cash Deposit is new (taxable) income to you. This new income needs to be declared and the taxes paid. If you Uncle is a close relative (the exact relationships that are called close relatives are defined by law), the return of the money can be declared to be a gift from your Uncle to you and no taxes are due from you on the money. If the funds are large, it is advised to have a gift deed. It is not a simple matter of creating a gift deed stating that your Uncle has given you a gift; your Uncle has to show how he acquired so many assets that he gave you some money as a gift and whether appropriate taxes were paid by him. If your Uncle is not a close relative, he can still gift you up to Rs 50,000 per year without you having to pay any income tax on the money received, but again, a gift deed would be needed to account for the cash deposits. In short, keep speaking to your CA. He will advise you on the best course of action. Related Question Transfering money from NRE account in India to family member", "title": "" }, { "docid": "16068", "text": "I have not opened any NRE/NRO account before coming to Finland. This is in violation of Foreign Exchange Management Act. Please get this regularized ASAP. All your savings account need to be converted to NRO. Shall I transfer funds from abroad to both NRE and NRO account or I can transfer only to NRE account in India? You can transfer to NRE or NRO. It is advisable to transfer into NRE as funds from here can be repatriated out of India without any paperwork. Funds from NRO account need paperwork to move out of India. I am a regular tax payer in abroad. The Funds which i'll transfer in future will attract any additional tax in India? As your status is Non Resident and the income is during that period, there is no tax applicable in India on this. Few Mutual Fund SIPs (monthly basis) are linked with my existing saving account in india. Do these SIPs will stop when the savings account will turn into NRO account? Shall I need to submit any documents for KYC compliance? If yes, to whom I should submit these? is there any possibility to submit it Online? Check your Bank / Mutual Fund company. Couple of FDs are also opened online and linked with this existing saving account. Do the maturity amount(s) subject to TDS or any tax implication such as 30.9% as this account will be turned into NRO account till that time and NRO account attracts this higher tax percentage. These are subject to taxes in India. This will be as per standard tax brackets. Which account (NRE/NRO) is better for paying EMIs for Home Loan, SIPs of Mutual Funds, utility bills in India, transfer money to relative's account etc Home Loan would be better from NRE account as if you sell the house, the EMI paid can be credited into NRE account and you can transfer this out of India without much paperwork. Same for SIP's. For other it doesn't really matter as it is an expense. Is there any charge to transfer fund from NRE to NRO account if both account maintain in same Bank same branch. Generally No. Check with your bank. Which Bank account's (NRE/NRO) debit/ATM card should be used in Abroad in case of emergency. Check with your bank. NRE funds are more easy. NRO there will be limits and reporting. Do my other savings accounts, maintained in different Banks, also need to be converted into NRO account? If yes, how can it be done from Abroad? Yes. ASAP. Quite a few leading banks allow you to do this if you are not present. Check you bank for guidance.", "title": "" }, { "docid": "448981", "text": "am I allowed to transfer into NRE account from paypal? Credits into NRE accounts are restricted. It has to be established that the funds being credited are income outside of India. In case of paypal, paypal uses local clearing to credit funds into Bank Accounts. So essentially one cannot credit NRE account by domestic clearing network like NEFT. It is best that you withdraw the funds into Bank Account outside India and use SWIFT or remittance service to credit your NRE account. I do not want to transfer to an NRO account since the money credited into it will become taxable. This is not the right assumption. Credits into NRO are not taxable by default; if you establish that the funds are from outside India, there is no tax on the income money transferred from abroad into the NRO account. However, the interest that will be paid by the bank on the balance of the NRO account is taxable income in India and is subject to TDS. In contrast, interest paid on the balance in an NRE account is not taxable in India and is not subject to TDS as long as you maintain NRI status. However it does make sense to keep accounts segregated, i.e. income generated in India, credit the NRO account and income generated outside India credit to NRE.", "title": "" }, { "docid": "263648", "text": "On my recent visit to the bank, I was told that money coming into the NRE account can only be foreign currency and for NRO accounts, the money can come in local currency but has to be a valid source of income (e.g. rent or investments in India). Yes this is correct as per FMEA regulation in India. Now if we use 3rd party remittances like Remitly or Transferwise etc, they usually covert the foreign currency into local currency like INR and then deposit it. The remittance services are better suited for transferring funds to Normal Savings accounts of your loved ones. Most remittance services would transfer funds using a domestic clearing network [NEFT] and hence the trace that funds originated outside of India is lost. There could be some generic remittance that may have direct tie-up with some banks to do direct transfers. How can we achieve this in either NRE/NRO accounts? If not, what are the other options ? You can do a Wire Transfer [SWIFT] from US to Indian NRE account. You can also use the remittance services [if available] from Banks where you hold NRE Account. For example RemittoIndia from HDFC for an NRE account in HDFC, or Money2India from ICICI for an NRE account in ICICI or QuickRemit from SBI etc. These would preserve the history that funds originated from outside India. Similarly you can also deposit a Foreign Currency Check into Indian Bank Account. The funds would take around month or so to get credited. All other funds can be deposited in NRO account.", "title": "" }, { "docid": "521753", "text": "I am on employment based visa in USA and want to send dollars from USA to India from my savings (after paying Tax). How much maximum dollars I can send in a day? month? or in a year regularly? There is no such limit. You can transfer as money you like to yourself anywhere. To pay the Bank Loan-student Loan how much maximum dollars I can send in a day, in a month or in a year? to pay that I have to pay directly to that Bank Account or in any account I can send money? You can transfer to your NRE account in India and move it further. You can also send it directly to the Loan Account [Check with the Bank, they may not be able to receive funds from outside for a Loan Account] My mother is having Green Card. She is not working. She has a NRE account in India. Can I send dollars from my USA Bank account to her NRE account in India? what are the rules for that? any Tax or limit for that? Or I have to get any permission before sending it? If you are sending money to your mother, it would come under Gift Tax act in US. There is no issue in India. Suggest you transfer to your own NRE account.", "title": "" }, { "docid": "495315", "text": "Is it possible to move money from NRE to NRO account Yes you can move money from NRE to NRO without any issue. You can't do the other way round. i.e. Move money from NRO to NRE. I would like to move USD earning to NRE Yes you can further move money in NRE to NRO account Yes you can I am planning to give NRO account to HDFC Home loan for EMI processing Yes you can. Depending on your long term plan it may not be a good idea. For example if you were to sell the house you cannot move the funds into NRE and outside of India without some amount of paperwork. However if you pay the EMI via NRE account, on the sale of house, you can transfer the funds into NRE account to the extent of the loan paid and the Original downpayment [if made from NRE account]. also I can deposit money from other savings account to NRO; As an NRI, you can't hold ordinary savings account in India. This is violation of norms. Please have any/all savings account in India converted to NRO at the earliest.", "title": "" }, { "docid": "307404", "text": "I am a non-resident alien transferring a limited amount ( in dollars post tax) to India every couple of months. Assuming you are transferring this into an NRE account in India or atleast NRO account in India. As a NRI, by regulations one should not hold normal Savings account. This has to be converted into NRO. I put that money as a fixed deposit in a bank (which gives 6-7 percent annual return) Assuming you have FCNR deposits. Also assuming that you are declaring the taxes in your US Tax returns and paying tax accordingly. There is no tax in India on FCNR. If this was in ordinary FD or in NRO account, you are declaring and paying taxes in India as well as in US. What is the max limit on transferring money back from India to USA? If you have transferred this into NRE account, there is no limit. Other account there is a limit. Read more at Liberalized Remittance Scheme and here. What are the legitimate ways to transfer the money? From India point of view, this has to be Bank to Bank transfers. You can't carry cash [Indian Rupees] outside of India beyond Rs 25000 [or 15000?]. You can't hold excess of USD 250 without valid purpose. Western Union is not authorized to transfer funds out of India. Will there be any tax levied? No assuming you are already paying taxes on the Interest in US and depending on the type of account in India.", "title": "" }, { "docid": "446647", "text": "I want to send some money to Indian in my saving account but I haven't any NRO/NRE account. It is advisable to Open an NRE account. As an NRI you cannot hold a savings account. Please have this converted into NRO account ASAP. Process or Transaction charges or Tax (levied by Indian bank) on money what I'll send to my saving account in India. I know the process or transaction charges (applied by UK banks) from UK to India. There will be a nominal charge levied by banks in India. If you use dedicated Remittance services [Most Leading Indian Banks offer this], these are mostly free. Is there any limit to get rid off tax? Nope there isn't any limit. This depends on service provider. What types of paper work I'll need to do for showing that income is sent from UK after paying tax. If you transfer to NRE account. There is no paperwork required. It is implicit. If not you have to establish that the funds are received from outside India, keep copies of the transfer request initiated, debits to the Bank Account in UK, your salary slips, Passport stamps etc.", "title": "" }, { "docid": "450925", "text": "How to send the full loan amount from Saudi Arabia (money exchange), because I have a money transfer limit? There is no limit for sending money into India. Just use the right banking channel and transfer the funds. If I sent to India, what about tax and all that in India? In a financial year if you are outside of India for more than 182 days, you are Non-Resident for tax purposes. Any money you earn outside of India is tax free in India. i.e. there is no tax for this funds in India. If it is possible to send the money, to whom do I have to send it (my account, or my parents account) Whatever is convenient, preferably to your own NRE/NRO account. Any documents I have to show for tax issues (in case tax) You have to establish that you are NRI and hence this funds are not taxable. Hence its best you transfer into NRE/NRO account. If you transfer to your parents account, you would need a gift deed to make this non-taxable to your parents. I have savings account my self in Axis Bank, for the past 3 years I am paying taxes, if I send to my Axis Bank account how can I withdraw the full amount (10 lakhs (1,000,000)) on single day Withdrawal is possible by cash or cheque You can write a check, do a NEFT/RTGS transfer to your loan account, you can withdraw cash by giving some notice time to the Branch Manager of your Branch.", "title": "" }, { "docid": "286825", "text": "There is no difference in taxation in India if you transfer every month or bulk. If you use specialized remittance services from leading Indian Banks, there would be little difference in fees. Assuming you are keeping the funds in NRE account in India and hold it in GBP, you get a slight better rate of interest that what you would get in UK. The interest would not be taxable in India, however it would be in UK. If you convert the funds at hold it in NRE, Rupee account, you would get still better rate of interest. However you are taking the Fx risk when you try and convert this back to GBP incase you decide to stay on. There are no right or wrong answers Edit: There is no limit on the amount of funds earned as NRE that can be got into India tax free. There is a time limit of 7 Years to get the funds back to India tax free. From a tax point of view if you transfer into NRE account its easy. If you transfer into Normal Savings account you would need some paperwork.", "title": "" }, { "docid": "354255", "text": "Will I able to put the Rs amount back in the NRE account the same amount which I have paid against that house? If you have purchased the property by debiting an NRE account [you should have the paper trail], the same amount of funds can be transferred back to NRE Account. For example the house was for 50 lacs, and you paid Rs 30 lacs from NRE account, when you sell the house, you can transfer back only 30 lacs into the NRE account. Will I need to pay TAX on NRE account money before transferring out of India? You need not pay tax on the funds in NRE account. However if you have made gains by buying and selling a house [irrespective of the source of funds], you have to pay capital gains tax.", "title": "" }, { "docid": "147197", "text": "Assuming that the NRE (NonResident External) account is in good standing, that is, you are still eligible to have an NRE account because your status as a NonResident of India has not changed in the interim, you can transfer money back from your NRE account to your US accounts without any problems. But be aware that you bear the risk of getting back a much smaller amount than you invested in the NRE account because of devaluation of the Indian Rupee (INR). NRE accounts are held in INR, and whatever amounts (in INR) that you choose to withdraw will be converted to US$ at the exchange rate then applicable. Depending on whether it is the Indian bank that is doing the conversion and sending money by wire to your US bank, or you are depositing a cheque in INR in your US bank, you may be charged miscellaneous service fees also. To answer a question that you have not asked as yet, there is no US tax on the transfer of the money. The interest paid on your deposits into the NRE account are not taxable income to you in India, but are taxable income to you in the US, and so I hope that you have been declaring this income each year on Schedule B of your income tax return, and also reporting that you have accounts held abroad, as required by US law. See for example, this question and its answer and also this question and its answer.", "title": "" }, { "docid": "78813", "text": "The simplest way is you transfer the funds into your NRE account in India. From the NRE account transfer the funds to your brother-in-law and show the purpose as Loan. From 2012 onwards RBI has simplified things under FMEA and your brother-in-law can deposit/repay the loan back into the NRE account. Once the funds are in NRE account you can repatriate then whenever you like. This entire process requires less paperwork. The option you have suggested is also fine, however your brother-in-law needs to engage the services of a CA and he will authenticate the purpose of remittance to the Bank. Based on this certificate the Bank will transfer the funds outside of India.", "title": "" }, { "docid": "586772", "text": "Citizens of India who are not residents to India (have NRI status) are not entitled to have ordinary savings accounts in India. If you have such accounts (e.g. left them behind to support your family while you are abroad), they need to be converted to NRO (NonResident Ordinary) accounts as soon as possible. Your bank will have forms for completion of this process. Any interest that these accounts earn will be taxable income to you in India, and possibly in the U.K. too, though tax treaties (or Double Taxation Avoidance Agreements) generally allow you to claim credit for taxes paid to other countries. Now, with regard to your question, NRIs are entitled to make deposits into NRO accounts as well as NRE (NonResident External) accounts. The differences are that money deposited into an NRE account, though converted to Indian Rupees, can be converted back very easily to foreign currency if need be. However, the re-conversion is at the exchange rate then in effect, and you may well lose that 10% interest earned because of a change in exchange rate. Devaluation of the Indian Rupee as occurred several times in the past 70 years. Once upon a time, it was essentially impossible to take money in an NRO account and convert it to foreign currency, but under the new recently introduced schemes, money in an NRO account can also be converted to foreign currencies, but it needs certification by a CA, and various forms to be filled out, and thus is more hassle. interest earned by the money in an NRE account is not taxable income in India, but is taxable income in the U.K. There is no taxable event (neither in U.K. nor in India) when you change an ordinary savings account held in India into an NRO account, or when you deposit money from abroad into an NRE or NRO account in an Indian bank. What is taxable is the interest that you receive from the Indian bank. In the case of an NRO account, what is deposited into your NRO account is the interest earned less the (Indian) income tax (usually 20%) deducted at the source (TDS) and sent to the Income Tax Authority on your behalf. In the case of an NRE account, the full amount of interest earned is deposited into the NRE account -- no TDS whatsoever. It is your responsibility to declare these amounts to the U.K. income tax authority (HM Revenue?) and pay any taxes due. Finally, you say that you recently moved to the U.K. for a job. If this is a temporary job and you might be back in India very soon, all the above might not be applicable to you since you would not be classified as an NRI at all.", "title": "" }, { "docid": "153528", "text": "For the financial year 1 April 2014 to 31 March 2015 as you have / will be spending more than 182 days outside of India, you are Non-Resident from tax point of view. For the period 1 April 2014 to Aug 2014, any salary / income you have earned in India is taxable and tax need to be paid. For the period Aug 2014 to 31 March 2015 the income you have earned in Saudi is not taxable in India. You can transfer money to India or keep in Saudi, it has no effect on the taxes. Any interest income you earn, or rental income you earn, or any other source of income in India is taxable. You would need to file returns accordingly. An NRE Accounts allows you to transfer funds out of India without any questions. So if you intend at some point in time in future to move funds out of India [say settling down in Saudi or UK or US etc] it is advisable to have NRE account. If you are sure you don't want to transfer funds out of India, you should open an NRO account.", "title": "" }, { "docid": "344290", "text": "foreign income, transfer it to my savings account in India Yes you can transfer to India. The right account would be NRO/NRE. As an NRI one should not hold a regular savings account. forum that foreign income is not taxable unless used to buy stocks, fds etc If you are an NRI, income earned outside of India is not taxable in India. However any income you generate in India is taxable, i.e. interest income, gains from shares etc. Do we need to pay taxes for the money transferred No tax if you are an NRI even if you transfer funds to India. Taxation does not depend on whether or not you transfer the money, it depends on your status used to pay home EMIs or principle amount? You can use the money for what ever you like.", "title": "" }, { "docid": "210853", "text": "Check with Lawyer and CA who deals with international laws. It maybe illegal in Saudi Arabia. From India tax point of view, any credits into NRE account is not taxable. However credits to friends/family will be treated as GIFT and friends/family will be liable to pay a gift tax if such transfer are more than Rs 50,000/- per year. Although FEMA does not prohibit explicitly such arrangement, these look like round about way of moving money and can be investigated.", "title": "" }, { "docid": "570639", "text": "\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"", "title": "" }, { "docid": "429271", "text": "What is the best and most economical way for me to pay the loan EMIs directly? (whether from a Singapore account or a NRE/NRO account) It is advisable to have it via the NRE account as this would be easier. If you already have funds in NRO account, you can use that before you use the funds from NRE account. For all expenses I make in India (e.g shopping, general expenses in India visits) what account should I be using, ideally? Is the route to transfer into NRE then NRO and then withdraw from NRO? Whatever is convenient. Both are fine. If I plan to make any investments in SIPs/Stock markets, should I link my NRE account with a demat account and directly use that? If I sell the shares will the earnings come back into NRO or NRE? You need to open a DEMAT PINS Account and link it to NRE account. You are sell and repatriate the funds without any issue from PINS account. Related question Indian Demat account", "title": "" }, { "docid": "260889", "text": "As NRI/PIO (Non-Resident Indian/Person of Indian Origin), the overseas income and transfers in foreign currency are exempt from Indian income taxes. However, the account in India has to be designated NRE or FCNR. There are three kind of accounts that an NRI can maintain Interest earned in NRE and FCNR accounts is exempt from income taxes. Interest earned in NRO accounts is not exempt from income taxes, in fact banks would withhold about 30% of interest (TDS). The exact tax liability would depend upon income generated in India and TDS could be applied towards that liability when the tax returns are filed. There are other implications also of designating the account as NRE or NRO. NRE accounts can only be funded via inward remittance of permitted foreign currency e.g. deposit USD/GBP. So proceeds like rental income, pension etc. that are generated in INR within India can't be deposited in this account. The money deposited in NRE account can grow tax free and can be converted back in any foreign currency freely. On the other hand NRO accounts can be funded through both inward remittance of permitted foreign currency or local income e.g. rental, pension etc. All the amount in this account is treated as Indian originated INR (even if remitted in foreign currency) and thus is taxed as any other bank account. The amount in this account is subject to the annual cap of convertibility of USD 1 million. Both NRE and NRO accounts are maintained in INR and can be Saving and Term Deposit. Any remittance made to these accounts in any foreign currency is converted to INR at the time of deposit and is maintained in INR. FCNR account are held in foreign currency and can only be Term Deposit. Official definitions: Accounts for Non Resident Indians (NRIs) and Persons of Indian Origin (PIOs)", "title": "" }, { "docid": "468462", "text": "Your bank will gladly help you convert your Indian savings accounts into NRO savings accounts. You cannot change these accounts into NRE accounts directly; NRE accounts are supposed to be funded via deposits made from foreign currency accounts. Under the liberalized schemes available now, you can transfer the money in your regular savings account into your account abroad, converting it into foreign currency, if you (and your CA) provide proof to your bank (and the Reserve Bank of India) that you have paid all applicable taxes on the money in your savings account. And then you can transfer it all back into your NRE account. Perhaps you can combine these two steps into a single one, thereby putting the money in your regular savings account into an NRE account in one step, but I am sure that there will be lots of fees involved (e.g. you might get whacked by commissions, as well as the exchange rate differential as if you converted Indian rupees to US dollars, say, and then converted the dollars back to rupees) just as if you did the two-step conversion. There are no taxes involved in moving your own money into different accounts but there can be lots of fees and service charges.", "title": "" }, { "docid": "271415", "text": "As an NRI, you can't hold a regular savings account. It should have been converted to NRO. Option 1: Open NRE account : Since I am relocating permanently this might not be good option for me as converting This is the best Option as funds into NRE are not taxable in India. The provides a clean paper trail so that if there are any tax queries, you can answer them easily. You can open a Rupee NRE account, move the funds. On return move the funds into Normal Savings account and close the NRE account. This is not much of hassle. Option 2: Create NRO account: There would be taxes on the interest earned of the funds. But I am not sure of this, since I will have been moved to India permanently would I need to still pay taxes on the interest earned while I am in India? Any interest in NRO or normal savings account is taxable in India. There is no exemption. Option 3: I can transfer my funds directly to my account in India but I believe I would have to pay tax on the the funds that I transfer and that would be double taxation. Which I think would be the worst option for me. Please correct me if I am wrong. This is incorrect. Any earnings outside of India when your status is NRI, is not taxable in India. Opening an NRE account provides proper paper trail of funds. As an NRI one cannot hold normal savings account. This should have been converted into an NRO account. Although there is no penalty prescribed, its violation of FEMA regulation. I also hope you were declaring any income in India, i.e. interest etc on savings and filing returns accordingly. Option 4: I can transfer the funds to my direct relatives account. I still believe there would be tax to be paid on the interest earned of the amount. You can transfer it to your parents / siblings / etc. This would come under gift tax purview and would not be taxable. They can then gift this back to you. However such transactions would appear to be evading regulations and may come under scrutiny. Interest on Savings account is taxable. So best is go with Option 1. No hassle. Else go with Option 3, but ensure that you have all the paperwork kept handy for next 7 years.", "title": "" }, { "docid": "232043", "text": "Is it liable for taxation in India? Taxation does not depend on whether to transfer money to India or keep it in GCC. It depends on your tax status. In a given Financial year; 1st April to 31st March, if you are outside of India for more than 182 days, your are Non-Resident Indian, NRI for tax purposes. If you are NRI, income earned outside of India is not taxable in India [even if you transfer the funds to India]. If you are not an NRI, you income in GCC will be taxable in India [Even if you keep the money in GCC]. We both send our salary into a friends account in India and then transfer an amount to our own accounts This is an incorrect practise, If you are NRI, you should not be holding a Savings account, it should be converted into NRO and you can if you want open an NRE account. For your friend where you are transferring money, if there is an income tax audit, there would be quite a few questions asked and your friend has to establish and keep records that this is not GIFT, but more of a convenience agreement.", "title": "" }, { "docid": "483081", "text": "1.What are the tax implications - income tax, gift tax, wealth tax etc. for the money credited in the NRO Account? As the funds are transferred by your wife to you, there is NO Income. Hence Income Tax rules don't apply. It would be treated as GIFT and come uder Gift Act. As per gift Act, one can transfer unlimited amount between close releatives. The defination of close relative as per Income Tax includes parents, spouse, siblings etc. The interest you earn in NRO account is taxable in India. 2.Can I transfer this money to my parents and would that attract any tax?. I understand my parents will have bear any tax based on income they earn on my transfer... Are there any tax implications for me? You can transfer this money to your parents. This will not be taxable to you. It will not be taxable to your parents as its Gift. Any income earned by your parents on this will ofcourse be taxable. 3.Can I move this money to NRE account and what is the process for that and how easy it is? Its best if you had your wife send funds into NRE account. Direct transfer as much as know is not allowed. Having said that, it is possible to transfer funds out of India via proper paperwork, there is also a limit [quite large] on the amount that can be transferred a year. Get a CA to help you with the paperwork.", "title": "" }, { "docid": "193842", "text": "You would need to pay tax on the 10% gain. Was this money loaned from your NRE account? Is there paperwork to show that there was this loan given? If yes then it would be easy to get this back into NRE account. Once in NRE account you can move this back to US without any issue. If not, then you can get this into NRO account. From NRO account you would need to consult a CA to do some paperwork [essentially certifying that you have paid all taxes due] so that funds can be remitted outside. Edit: Looks like you have completed all formalities. A credit to NRE Account can only happen from funds outside of India. However a credit from India into NRE account can happen under some circumstances, like Loan give and received back. You would need a CA in India to help you complete the formalities. The tax is due in India as this was due to gain in India. As you are US resident for tax purposes, and US taxes global income, this is taxable in US as well. You can claim relief in US to the extent of taxes paid in India. India and US have DTAA.", "title": "" }, { "docid": "355796", "text": "Can we wire transfer money from my NRE account to USA checking account? Yes you can Is there any restrictions for transferring money? Nothing in India Hopefully someone else will answer the US side of questions.", "title": "" }, { "docid": "452384", "text": "Can she send money to me in India through their NRI account? She can transfer the money to her NRE account and then to your Savings Account. Alternatively she can also transfer money directly to your savings account. There is no tax for this transaction in India as it is gift and exempt under gift tax act. If the amounts are large [run in quite a few tens of lacs], have some paperwork showing this as Gift. You can transfer this to son or doing anything you like with it.", "title": "" }, { "docid": "585947", "text": "Legally if you are NRI for tax purposes, then you are required to convert all your Savings Account into NRO accounts. For tax purposes it be advisable to open an NRE account. Depending on the Banks policy you can convert the account into NRO by submitted a scanned copy of passport along with the Visa page. You can transfer money from US to any Account in India [Savings/Current/NRO/NRE] using xoom or any other remittance services remit2india, money2india etc.", "title": "" }, { "docid": "9084", "text": "You can open a NRE account or a NRO account online before you leave the US and transfer the bulk of your money into it. After returning to India, your tax status will be RNOR (Resident but Not Ordinarily Resident) and you can keep the NRE and NRO accounts for several years (three?) and can do whatever you like with the money in them: transfer the money to ordinary (resident) savings accounts, or reconvert back to US dollars for payment of any outstanding bills (e.g. credit card bills) or US taxes for 2017 etc. Don't forget to close your US bank account before you leave. Many banks allow opening of NRE and NRO accounts on-line, though some paperwork needs to be sent in (e.g. copies of passport pages, signature cards etc). In most cases, one month is more than enough time to complete these formalities.", "title": "" }, { "docid": "448689", "text": "\"For the financial year 1 April 2014 to 31 March 2015, as you have [or will be] spent more than 182 days outside India, you would be treated as \"\"Non-Resident\"\" [NRI] for tax purposes. If you are NRI Show my Kuwaiti Income in my Income Tax Return? Pay any tax on the money that I am sending to savings bank accounts in India You need not Pay Tax on your income outside India. i.e. there is no tax obligation created. It cannot be declared in Tax Returns. However any interest you earn on the money deposited in India would be subject to taxes. Will my wife have to show the income and/or pay the income tax on the money that I am sending to her savings bank accounts? There is no Income to you wife [Income is something you earn] and hence its out of scope from Income Tax act. It would fall under gift tax rules. As per Gift Tax one can transfer unlimited funds between close relatives. Hence there is No tax. It would be better if you open an NRO/NRE account and transfer funds into that account\"", "title": "" } ]
2615	Earning salary from USA remotely from New Zealand?	[ { "docid": "593197", "text": "\"Can the companies from USA give job to me (I am from New Zealand)? Job as being employee - may be tricky. This depends on the labor laws in New Zealand, but most likely will trigger \"\"nexus\"\" clause and will force the employer to register in the country, which most won't want to do. Instead you can be hired as a contractor (i.e.: being self-employed, from NZ legal perspective). If so, what are the legal documents i have to provide to the USA for any taxes? If you're employed as a contractor, you'll need to provide form W8-BEN to your US employer on which you'll have to certify your tax status. Unless you're a US citizen/green card holder, you're probably a non-US person for tax purposes, and as such will not be paying any tax in the US as long as you work in New Zealand. If you travel to the US for work, things may become tricky, and tax treaties may be needed. Will I have to pay tax to New Zealand Government? Most likely, as a self-employed. Check how this works locally. As for recommendations, since these are highly subjective opinions that may change over time, they're considered off-topic here. Check on Yelp, Google, or any local NZ professional review site.\"", "title": "" }, { "docid": "322906", "text": "Yes. You must register for GST as well, if you will be making over the threshold (currently $60,000). That's probably a bonus for you, as your home office expenses will mostly include GST, but your income will most likely be zero-rated. Check with an accountant or with the IRD directly. Just be certain to put aside enough money from each payment to cover income tax, GST and ACC. You will get a very large bill in your second year of business.", "title": "" } ]	[ { "docid": "249604", "text": "Note: that the New Zealand CPI in 2014 Q2 is 1.6% Year on Year, that is it is the inflation rate from 2013 Q2 to 2014 Q2. The quarterly change from 2014 Q1 to 2014 Q2 is 0.3%. Check out this Inflation Calculator. At the same time the Official Interest Rate in New Zealand was just raised on 24th July 2014 by 25 basis points to 3.5%. So your savings in the bank at a rate of 4.5% is beating inflation, but once you deduct any tax from the interest earned, you are just beating the current inflation rate, which is not really a good long term investment choice.", "title": "" }, { "docid": "374391", "text": "\"Do you know how it cost the USA to build the national highway system? Do you know what is \"\"investment\"\"? Do you how much people pay (back) in taxes when they have a job and earn a salary (rather then get money from welfare)? Do you understand that in the Globalists world, the USA has to compete with salaries paid in China for their workers?\"", "title": "" }, { "docid": "26508", "text": "Because you actually reside in New Zealand, your income taxes will be paid in New Zealand. However, as a non-resident of Australia you will have tax withholding on all of the interest you earn in an Australian bank account. Obviously, because that tax is paid to Australia, that will not be counted against your New Zealand income taxes due to the taxation agreement between those countries. You should still discuss this with an accountant in New Zealand and consider acting as a sole trader. Since you are doing freelance work, that seems like the most logical setup anyway.", "title": "" }, { "docid": "12906", "text": "\"If you are a resident of New Zealand for tax purposes, you will be taxed in New Zealand on all of your \"\"worldwide income\"\". This is income derived from New Zealand as well as income derived from all other countries Source: http://www.ird.govt.nz/international/nzwithos/income/overseas-income-index.html Another link that will be of use is this: https://www.ato.gov.au/individuals/international-tax-for-individuals/work-out-your-tax-residency/ This is Australia's rules on if you qualify as a resident for tax purposes. I am not an accountant or a lawyer but my reading of this is you actually have to reside in Australia to be considered a resident - whether or not you have a bank account there doesn't appear to play into it. Additionally, Australia and NZ have a \"\"double taxation agreement\"\", explained here: http://www.ird.govt.nz/yoursituation-nonres/double-tax/ So this should prevent you from being taxed in both places.\"", "title": "" }, { "docid": "103030", "text": "In the United Kingdom, there is a leading company that has been offering Progressive business funding solutions to the businesses for the last 120 years. Their service areas are South Africa, New Zealand, Ireland, Canada, Australia, USA, etc.", "title": "" }, { "docid": "141551", "text": "In addition to all the other answers, here is a New Zealand Herald article from earlier this year about second mortgages, confirming that it is both legal and common in New Zealand. Whether or not it is a good idea in your situation is another question.", "title": "" }, { "docid": "393510", "text": "Pfft, you guys have got it easy. Here in good old New Zealand, we pay more for NZ milk and cheese etc. than you do for the same product in the USA and Australia. Good old Fonterra, taking the country for a ride since ages ago.", "title": "" }, { "docid": "59969", "text": "The primary difference between Japan and most other developed nations is who owns their debt. Japan's debt is almost entirely internal. That is it's actually borrowed from within Japan. It's not owned by China or anyone else. Additionally, Japan owns a fairly substantial proportion of the USA's debt which provides additional security. It's a favorite complaint of Romney and his friends that American is borrowing from China to finance public spending. A lot of people don't realize, that in fact Japan was until very recently, America's biggest source of borrowing. And is still number 2 by a substantial margin. Combine this with pretty careful regulation by the Bank of Japan, low bond yields, and a much larger economy, still with a decent manufacturing base, and Japan's situation isn't remotely like Greece despite it appearing worse. In a nutshell, the Japan is the educated university graduate with a reasonable income, who like many of us who buy a house that costs many multiples of our annual salary, and can afford to service the debt even if it needs to be carefully managed. Greece is the homeless, one-armed drug addict with no prospects that struggles to find a few bucks to spend a night in a hostel. The size of the debt is more or less irrelevant. It's the ability to pay it that really matters. Of course this doesn't mean that if circumstances change, things couldn't go south badly, but right now Japan isn't in trouble and the 230% vs 130% misrepresents the reality of the situation.", "title": "" }, { "docid": "232282", "text": "This question came up again (Living in Florida working remotely - NY employer withholds NYS taxes - Correct or Incorrect?) and the poster on the new version didn't find the existing answers to be adequate, so I'm adding a new answer. NYS will tax this income if the arrangement is for the convenience of the employee. If the arrangement is necessary to complete the work, then you should have no NYS tax. New York state taxes all New York-source salary and wage income of nonresident employees when the arrangement is for convenience rather than by necessity (Laws of New York, § 601(e), 20 NYCRR 132.18). Source: http://www.journalofaccountancy.com/issues/2009/jun/20091371.html Similar text can also be found here: http://www.koscpa.com/newsletter-article/state-tax-consequences-telecommuting/ The NYS tax document governing this situation seems to be TSB-M-06(5)I. I looked at this page from NYS that was mentioned in the answer by @littleadv. That language does at first glance seem to lead to a different answer, but the ruling in the tax memo seems to say that if you're out of state only for your convenience then the services were performed in NYS for NYS tax purpose. From the memo: However, any allowance claimed for days worked outside New York State must be based upon the performance of services which of necessity, as distinguished from convenience, obligate the employee to out-of- state duties in the service of his employer.", "title": "" }, { "docid": "481382", "text": "New Zealand Bank cannot directly ask Singapore Bank. They can approach courts in Singapore and request for funds. Given that amount is small, the cost for pursuing a court case in Singapore would be much higher and the Bank in New Zealand may have already written this off. They may still have reported you as a defaulter, depending on various things, you may not get a Visa to travel back into New Zealand, or get one and get arrested once you land in New Zealand even during transit.", "title": "" }, { "docid": "326970", "text": "In addition to D. Stanley's very fine answer, the price of stocks change as a result of changing market conditions and the resulting investor estimation of its effect on the company's future earnings. Take these examples. Right now, in the USA, there is a housing shortage; that is, there are fewer houses available for purchase than there are willing buyers. Investors will correctly assume that the future earnings of home builders will be higher than they were, say ten years ago. Seeking to capitalize on these higher earnings, they will try to buy the stocks. However, the current owners of the stock, potentially the sellers, know the same thing as the investor-buyer and therefore demand a premium to entice a sale. The price of the stock has risen. The reverse is true, also. Brick and mortar retailers are declining as more consumers prefer on-line retail shopping. The current owners of these stocks will probably want to sell their stock before it is worth even less. The investor-buyer also knows the same facts; that future earnings will most likely be less for these companies. The potential buyer offers a very low price to entice a sale. The price of the stock has fallen. Finally, the price of stocks rise and fall with general market conditions. As an example, assume that next months jobs report is released showing that 350,000 new jobs were created in July. Investors will believe that if companies are hiring, then the companies are doing well; they are selling products and services at a higher than expected rate, requiring that they add new employees. They will also conclude that those 350,000 new employees will be spending their salaries to buy not just food, clothing and shelter, but also a few luxuries like a newer car, a TV, perhaps even a new home (please see paragraph 2!). All of these companies will have more business, more earnings and, likely, a higher stock price.", "title": "" }, { "docid": "489614", "text": "\"You should ask your employer to issue an updated payslip showing the correct gross salary, deductions and net salary, and then repay to the employer the difference between the net salary in your old (wrong) pay slip and the new (correct) one. You should also get them to confirm that they have corrected any information they sent HMRC. At the end of the tax year, when you get a P60 showing your salary for the year, make sure that it is consistent with the corrected salary amount, and check that the tax it shows as being deducted is also correct for that gross salary for the year. If you are still employed by them then you could just ask them to withhold the overpayment in your next salary payment, at which point the income tax would sort itself out because PAYE is calculated based on cumulative totals. If the overpayment had happened at the end of the tax year (March) then there'd be some risk of it messing up your tax payments. In some cases it's also possible that withholding from the next salary payment could make a difference to the total national insurance you end up paying - broadly, if you earn below the \"\"Primary Threshold\"\" of £8164/year, you might lose out. If you earn close to the \"\"Upper Earnings Limit\"\" of £45000/year, you could end up gaining.\"", "title": "" }, { "docid": "287540", "text": "I still have my bank account active in usa. Can my company legally deposit my salary in my bank account? Of course they can. Where they deposit is of no consequence (in the US, may be in India). It is who they deposit it for that matters. You need to file form W8 with the company, and they may end up withholding portion of that pay for IRS. You'll need to talk to a tax adviser in India about how to report the income back at home, and you may need to talk to a tax adviser in the US about what to do if the company does indeed remit withholding from your earnings.", "title": "" }, { "docid": "301323", "text": "\"I work in analyzing economic development projects in the Midwest like this, and one of the most frustrating aspects of my job is when people try to distill and simplify complex financing structures for the sake of misleading others and furthering an agenda. It's not uncommon that I see small local blogs write articles saying something to the effect of \"\"Major Development Project Skips Paying the Taxes it Rightfully Owes!\"\" completely disregarding the fact that in most cases the local government's options are to either give the developer an incentive and make some additional money, or offer nothing and watch the developer walk away from the table for a different site the next county over. Most governments, given the choice, would take lowered tax payments and more jobs over no tax payments and no jobs. Since I was curious, I decided to do a quick back-of-the-envelope calculation of this project using a common economic impact model. I used a conservative assumption of 3,000 new jobs (the minimum Foxconn expects to have by 2020, and well below the maximum capacity of the factory) in the Audio and Video Equipment Manufacturing (6-digit NAICS code of 334310) industry, using the entire State of Wisconsin as a geography. This industry has average annual earnings in Wisconsin of $56,000, so I subtracted out $3,000 per job to make it in line with the article. I also used the liberal assumption that 100% of these jobs will be considered \"\"net new\"\" or that they won't be replacing or destroying any existing jobs within the state. The results: - Salaries alone will amount to about $160 million per year, assuming all workers receive the same salary of $53,000. - Indirect effects (basically new jobs and spending for other industries used to support and maintain the factory, that aren't directly employed by the factory itself) will add an additional $20 million in earnings annually. - Finally, induced effects (the economic impact of new employees spending their salaries within the economy) will add an additional $80 million. - Total change in jobs (including factory workers, maintenance and utility workers, and new workers in supply chain industries) is estimated as just north of 5,000. This adds up to $260 million in additional annual earnings within the Wisconsin economy. There is a lot more to be considered when looking at a project like this, and there are a lot of ways Wisconsin or Foxconn can fuck this all up, but it isn't out of the realm of possibility that attracting this new plant will end up being a worthwhile plan for Wisconsin. Also, this quote: >“We are calling this development ‘Wisconn Valley,’ ” he said, speaking from the East Room of the White House, “because we believe this will have a transformational effect on Wisconsin just as Silicon Valley transformed the San Francisco Bay area.” Sounds like bullshit. Silicon Valley is largely research and development, not manufacturing. Saying that you'll replicate the success of software engineers earning $120k a year by bringing in more $50k a year manufacturing jobs is misleading at best.\"", "title": "" }, { "docid": "497946", "text": "As you're working, you and your spouse were probably born after 1935, so I'll assume that Marriage Allowance is relevant to you rather than Married Couple's Allowance. The allowance applies if your husband or wife earns less than the personal allowance in salary (£10,600/year), and less than £5,000/year in savings interest. For example it's likely this will apply if he or she's not working. Also, you need to be only a basic rate taxpayer, earning less than £42,385/year. In that case they can register online to transfer £1,060 of their personal allowance to you, which will reduce your tax bill by £212/year if you yourself earn more than £1,060 above the personal allowance. This will usually work by HMRC issuing a new tax code to your employer who will then automatically withhold less of your salary. You can't get your employer to do this directly, you have to go via HMRC. The allowance change will be effective as if from the start of the curren tax year in April 2015, so you will probably end up getting the proportion of the £212 that you could have had up till now (from April to August) back all at once in your next pay cheque, or possibly spread out over the rest of the tax year. Apart from that you'll get it spread out evenly over the year - i.e. about £17/month.", "title": "" }, { "docid": "436489", "text": "That is utter horseshit. There isn't a first world nation anywhere in which there is a black majority. From Madagascar to Jamaica. And for whites? From new Zealand to America, the exact opposite. I'm willing to have my mind changed. If someone can explain why that is the case, I'm more than open to hearing it. But from where I sit, it seems extremely self evident.", "title": "" }, { "docid": "375423", "text": "\"Even though you will meet the physical presence test, you cannot claim the FEIE because your tax home will remain the US. From the IRS: Your tax home is the general area of your main place of business, employment, or post of duty, regardless of where you maintain your family home. Your tax home is the place where you are permanently or indefinitely engaged to work as an employee or self-employed individual. Having a \"\"tax home\"\" in a given location does not necessarily mean that the given location is your residence or domicile for tax purposes. ... You are not considered to have a tax home in a foreign country for any period in which your abode is in the United States. However, your abode is not necessarily in the United States while you are temporarily in the United States. Your abode is also not necessarily in the United States merely because you maintain a dwelling in the United States, whether or not your spouse or dependents use the dwelling. ... The location of your tax home often depends on whether your assignment is temporary or indefinite. If you are temporarily absent from your tax home in the United States on business, you may be able to deduct your away from home expenses (for travel, meals, and lodging) but you would not qualify for the foreign earned income exclusion. If your new work assignment is for an indefinite period, your new place of employment becomes your tax home, and you would not be able to deduct any of the related expenses that you have in the general area of this new work assignment. If your new tax home is in a foreign country and you meet the other requirements, your earnings may qualify for the foreign earned income exclusion. If you expect your employment away from home in a single location to last, and it does last, for 1 year or less, it is temporary unless facts and circumstances indicate otherwise. If you expect it to last for more than 1 year, it is indefinite. If you expect your employment to last for 1 year or less, but at some later date you expect it to last longer than 1 year, it is temporary (in the absence of facts and circumstances indicating otherwise) until your expectation changes. For guidance on how to determine your tax home refer to Revenue Ruling 93-86. Your main place of business is in the US and this will not change, because your business isn't relocating. If you are intending to work remotely while you are abroad, you should get educated on the relevant laws on where you are going. Most countries don't take kindly to unauthorized work being performed by foreign visitors. And yes, even though you aren't generating income or involving anyone in their country, the authorities still well may disapprove of your working. My answer to a very similar question on Expatriates.\"", "title": "" }, { "docid": "396762", "text": "> someone can explain why that is the case Can you explain your case? What is your point? >There isn't a first world nation anywhere in which there is a black majority. From Madagascar to Jamaica. And for whites? From new Zealand to America, the exact opposite. These are supporting statements for what, exactly? Are you here to make the argument that white people are better than black people at nation building?", "title": "" }, { "docid": "361208", "text": "\"how many of those Indians were immigrants as opposed to born in the USA? there are tough restrictions for anyone to move from India to USA - only college graduated, high earning people can go to USA to work. the other groups might have born there and that's why they bring down the \"\"college-educated\"\" statistics.\"", "title": "" }, { "docid": "513921", "text": "\"P/E is price to earnings, or the price of the company divided by annual earnings. Earnings, as reported, are reported on accrual basis. Accrual basis accounting is...without going too deep, like taking a timeline, chopping it up and throwing different bits and pieces of every year into different piles. Costs from 2008 might show up in 2011, or the company might take costs in 2011 that aren't necessarily costs until 2012. Examples would include one-time charges for specific investments, like new shipping centers, servers for their hosting services, etc. Free cash flow is the amount of cash Amazon is generating from its operations. Free cash flow is almost always different from earnings because it's the amount of Earnings + adjustments for non-cash activities - capital expenditures (long-term investments.) Earnings is one thing. Cash generation is a completely different animal. There are plenty of companies that \"\"earn\"\" billions, but only have a few hundred million in cash to show for it because their earnings have to be reinvested into new stuff to grow/maintain the business. To have a free cash flow yield of 2.5% is to have a company valued at $40 for each $1 of free cash flow that the company generates each year. $1/$40 = 2.5%. SGA = Selling, General, & Administrative expenses. These are the costs of running the company - paying salaries, advertising, etc. This cost is second only to COGS, which is Cost of Goods Sold. Currently, Amazon pays $.774 for every $1 product it sells. Its operations add another ~$.20 to that total. After taxes, Amazon keeps about 2 cents of every dollar's worth of product it sells. This 2 cents is Amazon's net margin of 2%. Net margin is (net income)/(sales). If Amazon earned $3 for every $100 in sales it would have a net margin of 3%. Let me know if this makes no sense. If there's anything in particular that is especially confusing, definitely reply and I'll better clarify on specific items. Fire away with any questions, also. I love to discuss finance and accounting.\"", "title": "" }, { "docid": "230993", "text": "Keep in mind that this only really affects a few European nations, and we currently have a surplus. We’ve seen a rise of popularity of wine from other countries such as Australia and New Zealand, so it might only be region-specific wines that’ll be noticeably affected (such as Champagne for example).", "title": "" }, { "docid": "170143", "text": "In the UK, recent changes to pension taxation mean that from April 2011, people earning between £150,000 and £180,000 total and making large pension contributions (>£50,000 or so) will pay a marginal tax rate on additional salary of >100%. This is because pension contributions normally attract tax relief at the highest marginal rate - i.e. 40% if the gross salary is above about £40,000, and 50% for salaries above £150,000. But after April 2011, the rate of relief will be tapered down for gross salaries above £150,000, reaching 20% for a gross salary of £180,000. So for example if you earn £175,000 and make a contribution of £50,000, then an additional £1,000 in salary will incur £500 of direct tax, and also lead to a 1% reduction in tax relief (from 25% to 24%), costing another £500. Once you factor in National Insurance of another 1% or so, the net effect of the pay rise is negative.", "title": "" }, { "docid": "591770", "text": "Dr Stephen Augustine New Zealand As a previous coach of a youth rugby team in New Zealand, Dr. Stephen Augustine is all too familiar with the perceived risks and myths that are associated with the sport. The following are a few of the most common myths that Dr. Augustine would like to debunk.", "title": "" }, { "docid": "150347", "text": "How would the RRSP know where the money came from? You have two separate financial operations going on: You invest some money, within the limits set by the law, in a Tax Free Savings Account. Near the end of the year, you take the money, plus interest, out of the account. As you may guess by the name, you need not report the interest as income. There are no restrictions on the money, except that you can't put it back in the TFSA until the new year. The money is not segregated, or frozen, or marked with an exploding dye-pack. It's just money in your regular bank account, or your pocket, or under your mattress. During that year, you also work for a salary. Some is deducted from your salary to prepay your tax responsibilities, subject to a final calculation . You spend some and save some. The money you save also goes into your bank account, your pocket, or under your mattress. You can even take some of your money from your chosen repository and put it in a RRSP, which postpones the need to pay tax on the original deposit and on any earnings on the deposit. The money you take has lost all sense of identity: it isn't TFSA money or salary, or paper route money, or twelfth birthday money. It's just money...", "title": "" }, { "docid": "91541", "text": "Meth Testing New Zealand offers a cost-effective, fast and trustworthy meth sampling service. Not only does the service provide the technical skills to get the job done, we are experts in how this issue can impact residential tenancies and will guide clients through the process from start to finish.", "title": "" }, { "docid": "187763", "text": "Your experience supports my point, though. New Zealand is currently freer, economically speaking than America. According to an annual report published by the Heritage Foundation in America, New Zealand is in 3rd place globally. America is 17th. You actually have far less government than we do.", "title": "" }, { "docid": "423628", "text": "A: Rollover the cash from the previous account into the new one a low-cost IRA like Vanguard. This, and only this. Because your mortgage is, less than 4%, while your retirement plan will earn 7% over the long term. I have no 'retirement' plans because Because you're 28. and essentially will be happy working until I die Unless circumstances change. but as far as I see it this is not such a bad deal because it is like paying taxes on income. (Principal says I will lose up to 30%) You're ignoring the 10% early withdrawal penalty. I am wise with my money for the most part Then don't piss away $3,000 just for a temporary feel good. I earn a high salary in a tech job. As a result of being under 20%, I am paying mortgage insurance of about $300/mo. So -- after building up an Emergency Fund -- throw as much as possible of your high salary against your mortgage to get rid of the PMI.", "title": "" }, { "docid": "392187", "text": "\"Best Buy's customer service tomfuckery is the sole reason I will never set foot in one of their stores, ever again. Several years, and two TVs ago, I purchased a floor model on sale. While I didn't expect much, it was cheap. One of the things I asked _specifically_ about was the remote. The salesman assured me the remote was there. I said okay and we got the thing finagled off the wall and he went looking for the remote for 30 minutes. Came back with a remote with the same brand as the TV, and said, \"\"Here it is, it was mislabeled.\"\" We did some rudimentary tests in store -- power on, channel flip, etc. Seemed to work. Got it home, remote only worked for those basic functions -- power, channel, volume. Anything else didn't, including the number pad, or the various \"\"launch netflix\"\" buttons, etc. Did some research, the remote was for a different line. So I went back to Best Buy, with the remote, and told my tale. I asked for the reasonable: The remote for the TV itself, or for Best Buy to order the remote from the manufacturer. It was literally a $20 part, which I could've done, but they said they'd take care of it. I even had the part number, and shit. All they had to do was call the number, give them a card # and a shipping address and I would've been happy. I got, delivered to my door, in order: * One order, COD to my home. I refused delivery. * A box with 3 remotes, the same model as the one I originally got, which was not the right remote. I sent those back. * A box with a Logitech universal remote (really nice, but I already had one by that point), I sent it back. * A \"\"we're sorry\"\" letter, and a coupon for like 20% up to $500 at Best Buy. I sealed it back up and wrote \"\"return to sender, not a remote\"\" on it, and sent it back. Finally, after almost three months, a lady from the \"\"office of the President\"\" (at Best Buy) _called_ me, apologized profusely, conferenced in a rep from the manufacturer, and ordered the fucking remote with me on the phone. I can only image the amount of money and time they wasted trying to save $20. Fuck 'em.\"", "title": "" }, { "docid": "565778", "text": "Yes, and Japan's population density of 336 people per square kilometer makes that feasible. New Zealand's population density is relatively low, at 17.9 per square kilometer. While Auckland housing prices have been steadily increasing for decades, New Zealand has only just been experiencing a population boom driven by immigration that would make it necessary to build upwards.", "title": "" }, { "docid": "346228", "text": "H1B visas are not terrible, and I am not against all H1B visas. However, it is a bald faced lie to suggest the number 1, if not only, reason companies use them is to cut labor costs. These companies are not advertising they could have hired local talent, but chose to provide the job to someone from a poorer region. I think whatever city everybody in the world wants to work or go to school, like Tokyo or London or Paris or Boston, that is going to have the world's best talent. Also, if those people go back to their homelands, they don't bring with them the ideas from the city they worked or matriculated, but rather the best ideas from all over the world. That isn't at all what is happening in technology. There are plenty of computer science and electrical engineer majors in the USA out of work, and some making six figures with a BS degree and 3 years experience, but so many are out of work. Many of those jobs were outsourced, but the talent used was so poor, the cost to upkeep or update was so expensive, that many companies brought back the jobs to the USA. Those companies still want to hire the same low cost workers, but want them working in the USA for reasons I will spare, here. The USA talent pool is so full, and jobs so scarce, it drives down wages; not actually, because what really happens in the company is toxic to work for, and demands 16 hour days, 7 days a week, for the same great salary that may have once been 40 hours a week with fun puzzles and entertainment and space and a gym on site, etc. Stopping H1B visas would force companies to bring back their on site gyms, large break rooms, increase work life balance, etc. Stopping H1B visas mean a lot of billion dollar tech companies would have to pay their shareholders and executives less this year than last year, which is outrageous in the race to the bottom", "title": "" } ]
5ab73b655542992aa3b8c7e3	Are the cities of Huludao and Qian'an, Hebei both located in China?	[ { "docid": "2417785", "text": "Huludao () is a prefecture-level city in southwestern Liaoning province, People's Republic of China, bordering Hebei to the southwest. It is one of the two principal cities, along with Jinzhou, in the Liaoxi Corridor. Known as Jinxi (锦西 ) until 1994, Huludao has a total area of 10,415 km2 and a population of 2.87 million, of whom some 531,000 live in the city proper. Its name literally means \"Gourd Island\".", "title": "" }, { "docid": "24689369", "text": "Qian'an () is a city in the northeastern part of Hebei province in North China. It is under the administration of Tangshan City.", "title": "" } ]	[ { "docid": "2914986", "text": "Suizhong County () is a county of southwestern Liaoning, People's Republic of China. It is located on the northern coast of the Bohai Sea and is the southernmost county of Huludao City (as well as non-peninsular Liaoning), bordering Hebei to the southwest. The county has an area of 2765 km2 , a population of 640,000, and is an economically important region within Huludao. Suizhong is the home of the first Chinese citizen to travel in space, Yang Liwei.", "title": "" }, { "docid": "24479568", "text": "Jianchang () is a county of Huludao City in the southwest of Liaoning province, China. It is the largest division of Huludao, with an area of 3195 km2 , and population of 600,000 , located in mountainous terrain 85 km west of that city, serviced by China National Highway 306.", "title": "" }, { "docid": "24689332", "text": "Qinglong Manchu Autonomous County () is a Manchu autonomous county of northeastern Hebei province, China, bordering Liaoning to the north and east and located in the eastern part of the Yan Mountains. It is under the administration of Qinhuangdao City, and, , had a population of 520,000 residing in an area of 3309 km2 . Bordering county-level divisions are: Lingyuan and Jianchang County (Liaoning) to the north, Liaoning's Suizhong County and Qinhuangdao city proper to the east, Qian'an and Lulong County to the south, and Kuancheng Manchu Autonomous County and Qianxi County to the west.", "title": "" }, { "docid": "24749089", "text": "Lianshan District () is a district under the administration of the city of Huludao, Liaoning, People's Republic of China. It is located in the northeastern corner of Huludao prefecture, bordering Jinzhou. It has a total area of 1651 sqkm , and along with Longgang District is one of the two districts within which Huludao city itself is situated.", "title": "" }, { "docid": "24732654", "text": "Qian'an may refer to the following locations in China:", "title": "" }, { "docid": "24749088", "text": "Longgang District () is a district of Huludao, Liaoning, People's Republic of China. It is by far the smallest division of Huludao City with an area of just 138 km2 , and along with Lianshan District is one of the two districts within which Huludao city itself is situated.", "title": "" }, { "docid": "24704784", "text": "Qian'an County () is a county of northwestern Jilin province, China. It is under the administration of Songyuan City, with a 2002 population of 300,000 and an area of 3522 km2 .", "title": "" }, { "docid": "26328347", "text": "The Huludao North Railway Station is a railway station of Qinshen Passenger Railway that located in People's Republic of China.", "title": "" }, { "docid": "24749093", "text": "Nanpiao District () is a district under the administration of the city of Huludao, Liaoning, People's Republic of China. It is a mostly rural district containing no large urban centres, and comprises an area of 512 km2 , in the north of Huludao prefecture.", "title": "" }, { "docid": "919089", "text": "Hebei Medical University () is a university in Shijiazhuang, Hebei, People's Republic of China, under the provincial government. Located in Shijiazhuang, the capital city of Hebei Province which is 4 hours away from Beijing by car and 1 and a half hours by train. Hebei Medical University Established in 1894, it is one of the oldest and AAA graded medical schools in China.", "title": "" }, { "docid": "24690706", "text": "Ningjin County () is a county of southern Hebei province, China. It is under the administration of Xingtai City, with a population of 730,000 residing in an area of 1107 km2 . Both and G20 Qingdao–Yinchuan Expressway and China National Highway 308 pass through the county.", "title": "" }, { "docid": "9496471", "text": "Shijiazhuang Zhengding International Airport (IATA: SJW, ICAO: ZBSJ) is the primary airport serving Shijiazhuang, the capital of Hebei province, China. The airport is the hub for Hebei Airlines and a focus city for both China United Airlines and Spring Airlines. It is also the sole airport in China that Antonov An-225 can operate.", "title": "" }, { "docid": "42071902", "text": "The Huludao City Sports Centre Stadium is a stadium in Huludao which has a capacity of 32,000.", "title": "" }, { "docid": "8932426", "text": "Xingcheng (), former name Ningyuan (宁远), is a county-level city of southwest Liaoning province, China, with a population of approximately 140,000 urban inhabitants, and is located on the Liaodong Bay, i.e. the northern coast of the Bohai Sea. Currently under the administration of Huludao City, the area is steeped in history, and contains one of the best preserved Ming Dynasty towns in China, as well as functioning as a laidback summer resort.", "title": "" }, { "docid": "41557863", "text": "The Port of Huludao is an artificial deep-water international seaport on the coast of Huludao, Liaoning, People's Republic of China, on the Liaodong Bay. It is one of several smaller ports being rapidly expanded in Liaoning Province in order to service the Northeast.", "title": "" }, { "docid": "44955850", "text": "The Hebei Museum () is located in Shijiazhuang, the capital city of Hebei Province, China. It first opened in April 1953 in Baoding. After moving twice in the 1980s, it reopened in October 1987 at its present location on South Zhongshan Street. As the only provincial-level museum in Hebei, its primary function is the collection and exhibition of ancient cultural relics.", "title": "" }, { "docid": "919251", "text": "North China University of Science and Technology is a university in Tangshan City, Hebei Province, People's Republic of China.North China University of Science and Technology, located in Tangshan the most promising city at the center of Bohai Bay Rim, is one of the ten key universities of Hebei Province, China. It is a comprehensive university taking engineering and medicine as the backbone and pursuing a harmonious development of engineering, medicine, sciences, economics, management, law and humanities. Education programs are provided for masters, bachelors, international students and adult students.", "title": "" }, { "docid": "32787788", "text": "Huapi () is a town of Xinle City in southwestern Hebei province, China, located 11 km southwest of downtown Xinle. , it has 13 villages under its administration.", "title": "" }, { "docid": "32787771", "text": "Hantai () is a town under the administration of Xinle City in southwestern Hebei province, China, located 14 km east-southeast of downtown Xinle. , it has 19 villages under its administration.", "title": "" }, { "docid": "24690710", "text": "Xinhe () is a county of southern Hebei province, China, located on the Fuyang River (滏阳河), which is part of the Hai River watershed. It is under the administration of Xingtai City, with a population of 170,000 residing in an area of 366 km2 . The county is served by G20 Qingdao–Yinchuan Expressway and China National Highway 308.", "title": "" }, { "docid": "9806349", "text": "Yutian () is a county of northeastern Hebei province, China, and is under the administration of the prefecture-level city of Tangshan, bordering Tianjin to the north and west. It is located approximately 55 km northwest of Tangshan and 110 km east of Beijing, lying on China National Highway 102. It has an area of 1,165 km² and a population of 650,000 .", "title": "" }, { "docid": "23195902", "text": "Gu'an () is a county of Hebei province, China, bordering Beijing to the north. It is under the jurisdiction of Langfang City, with direct access to central Beijing via both G45 Daqing–Guangzhou Expressway and China National Highway 106.", "title": "" }, { "docid": "18142347", "text": "Wuqiang County () is county of southeastern Hebei province, China. It is under the administration of Hengshui City, with a population of 210,000 residing in an area of 442 km2 . Both China National Highway 307 and G1811 Huanghua–Shijiazhuang Expressway pass through the county.", "title": "" }, { "docid": "24662183", "text": "Pingshan County, Hebei () is a county of Hebei, China. It is under the administration of the Shijiazhuang city.", "title": "" }, { "docid": "24689330", "text": "Changli () is a county of northeastern Hebei province, China, with some Bohai Sea coast. It is under the administration of the Qinhuangdao City, and borders Funing County and Luan County. Both Beijing–Harbin Railway and China National Highway 205 pass through this county.", "title": "" }, { "docid": "32787568", "text": "Gangshang () is a town under the administration of Gaocheng City in southwestern Hebei province, China, located approximately halfway between Shijiazhuang and Gaocheng and just south of G1811 Huanghua–Shijiazhuang Expressway. , it has 11 villages under its administration.", "title": "" }, { "docid": "3237076", "text": "Ruyi Lake () is located near the city of Chengde, Hebei, in China.", "title": "" }, { "docid": "17748196", "text": "Huanghua () is a county-level city located in the Bohai Gulf coastal region of Hebei province, China. It is under the jurisdiction of Cangzhou City.", "title": "" }, { "docid": "24690736", "text": "She County (), or Shexian, is a county of southwestern Hebei province, China, located on the lower reaches of the Zhang River and bordering Shanxi to the west and Henan to the south. It is under the administration of the Handan City, with a population of 400,000 residing in an area of 1509 km2 .", "title": "" }, { "docid": "32787606", "text": "Huaishu () is a town under the administration of Jinzhou City in southwestern Hebei province, China, located about 6 km north-northeast of downtown Jinzhou opposite G1811 Huanghua–Shijiazhuang Expressway. , it has 18 villages under its administration.", "title": "" } ]
3967	Real estate agent best practice	[ { "docid": "311655", "text": "\"There are people that make up a small segment of the population that have an unsatisfied need to see the insides of other people's houses. There's also a segment of the population that don't quite understand the \"\"big picture\"\" of how service professions work... for example, any group of friends going into a restaurant and requesting a table and sitting at it for over an hour, but feel they don't need to leave a tip because they only ordered espressos or shared a desert. Sure, you're paying for the service of a service professional, but it should also include their time and resources you consume outside of the actual service but many don't have that perspective. Why should I pay you if you aren't providing your actual \"\"service\"\" to me even though I'm consuming your time and resources that would be earning you your expected salary otherwise, is their justification. So when you encounter an individual from both small segments of the population mentioned above, the result is the problem your wife faces with perspective buyers. I look at the Agent / Buyer relationship from a different perspective when I encounter these no-harm intended individuals. I don't see it as the buyer is hiring the agent... for if that was the case, a contract of some sorts would be involved detailing the menu of services provided by the agent with associated costs, the buyer would make selections from the menu, pay the costs, and services rendered. but that's not how it works. so its important to understand the perspective of the agent looking to hire the buyer.. you're not paying the buyer to be your client, but you are looking to select the prospective buyer that's going to generate cash flow. In a commissions based work force that is also your main source of income, you have to look at prospective clients as that.. simply prospects..but who are a vital component of your salary. So when allocating your time and resources, especially if you're dealing with several prospects, you literally have to turn away these cold leads who are just looking for design tips and paint color pattern suggestions and you as their escort. If I was in the shoe-making business, i wouldn't hire a walk-in, give him access to materials and work space with the assumption that if its to his liking, it'll generate profit towards my salary needs, if the only thing he's interested in doing is looking around at all the other shoes, a behavior that requires my presence, time, and resources. You almost can't even justify it as \"\"looking at it as possible income in the future\"\" if it's costing you revenue now, whether its in the form of having to neglect actual buyers or you could be investing your time in things that would impact salary needs, such as advance course work (attending optional trainings offered by your broker), or investing time finding more serious leads.\"", "title": "" }, { "docid": "479616", "text": "This question is a bit off-topic, might be better moved to another SE site. But I'll answer anyway: Sounds like the problem is that your wife is potentially being taken advantage of by people who may not really be prospects. Keep in mind no one can take advantage of you without your permission. There are also some things you and she can do to reduce the amount of wasted time while minimizing the risk of giving up on a potential sale. Qualify your leads: make sure these potential clients are really, truly potential customers. Ask whatever questions you have to ask in order to qualify them as real house hunters. It doesn't have to be binary: you can have hot leads ready to buy now, and lukewarm leads who may not buy for 12 months or more. Treat each one accordingly. Set limits: a lukewarm lead is not allowed to call you 20 times a day. Answer their calls just once per day. By answering the phone every time they call you are training them to call as often as they like! If you only return calls once per day they'll quickly learn to save their questions up and ask them all at once. Showing 10 houses sounds a bit silly. How can you remember any details after seeing 10 houses? By asking more questions and learning more about what your clients want in a house, you can reduce the footwork. Me, I'd flat out limit it to three houses per outing, and I wouldn't even hesitate to tell the client why. I think all these things will come in time. Like any new venture, she needs some experience to learn how to maximize her efficiency and effectiveness. Keep in mind it's better to have the phone ringing too much than not at all!", "title": "" } ]	[ { "docid": "565868", "text": "My question is... how is this new value determined? Does it go off of the tax appraised value? The tax assessors values are based on broad averages and are not very useful in determining actual home value. The most defensible valuation outside of a sale is a professional appraisal, real-estate agents may or may not give you reasonable estimates, but their opinions are less valuable than that of a professional appraiser. Additionally, agents hoping to land you as a client (even if you tell them you're not trying to sell) could be motivated to over-estimate. In many instances a few opinions from agents will be good enough, but if there is any contention a professional appraisal will be better. Should you, prior to your death, get an independent appraiser to appraise the value of the property and include that assessment of the properties value with the will or something? The real-estate market fluctuates too much to make having an appraisal done prior to your death a practical approach in most circumstances. You could make arrangements so that an appraisal would be scheduled after your death. Here's a good resource on the topic: Estimating the Value of Inherited Real Estate", "title": "" }, { "docid": "344186", "text": "There are multiple ways of determining the value of an inherited property. If you aren't planning on selling it, then the best way would be to have a real estate agent do a comp on the property (or multiple real estate agents).", "title": "" }, { "docid": "534095", "text": "The services provided by a real estate agent is known to be quite helpful when it comes to the aspect of Achieving a Vibrant Neighbourhoods in Mooloolaba with the Help of Real Estate Agents. They are known to provide us with the best suitable deals and offers.", "title": "" }, { "docid": "283494", "text": "We provide complete legal counsel in Real estate, VISA and much more, including representation before administrative and judicial labor authorities. Obtention of work permits for foreigners, legal representation during labor conflicts. The real estate closing process centers around and depends upon the closing agent, the seller and buyer should strive to obtain the best qualified, most experienced, most efficient, and most trustworthy agent that they can obtain.", "title": "" }, { "docid": "234585", "text": "RealConnect is a unique independent real estate company which connects residential & commercial property owners & investors to real estate agents and property managers. We operate Australia wide & have registered agents waiting to offer their services from most areas across the country. We have a keen passion to create an easy to use, low cost system to benefit everyone dealing in the real estate industry. We aim to increase profits for property owners as well as real estate agents by lowering the business expenses for the agents and allowing them to offer the same service to property owners for less.", "title": "" }, { "docid": "491829", "text": "\"On your tax return's Schedule C, Line B, you need to enter the Principal Business or Professional Activity Code that corresponds to your business's activities. There is a list of these 6-digit codes at the end of the Schedule C instructions. (HTML version here, or you can look at the last two pages of the PDF version.) The directions at the top of this list reads: Select the category that best describes your primary business activity (for example, Real Estate). Then select the activity that best identifies the principal source of your sales or receipts (for example, real estate agent). Now find the six-digit code assigned to this activity (for example, 531210, the code for offices of real estate agents and brokers) and enter it on Schedule C or C-EZ, line B. (Emphasis mine.) Although there are a lot of codes, it is entirely possible that you won't find one that exactly matches what you do. The directions say to pick the \"\"best\"\" one that you can. First, pick the broad category. You haven't specified your business, but let's say that you are a freelance programmer (a common occupation for Stack Exchange users). The category you decide is best might be \"\"Professional, Scientific, & Technical Services.\"\" There are several subcategories and activity codes under this, and you might find one that fits your business. However, if you don't, at the end of most categories, there is an \"\"Other\"\" code. For our example, there is code 541990, which is \"\"All other professional, scientific, & technical services.\"\" If you can't even find a broad category that describes your business, there is the last code in the list: 999999, which is for \"\"Unclassified establishments (unable to classify).\"\"\"", "title": "" }, { "docid": "237622", "text": "List your property in Puyallup WA in our database and sell your home at the best price. Leske Realty is the leading real estate agent in the region and over the years we have helped many buyers and sellers to achieve their real estate goals.", "title": "" }, { "docid": "298574", "text": "Usually if the property is part of a strata then the water rates get sent to the owner each quarter to pay and the usage for the whole complex is paid by the strata. So in this type of situation your tenant would not have to pay any water usage. If for some reason, as you mentioned, your unit, although part of a strata complex, is individually metered and you receive a water bill for both water rates and water usage, then the tenant would be liable to pay the water usage portion. This can usually be arranged by either giving the tenant a copy of the water bill with the amount of usage payable, or organising with the water company to separately sending the tenant the usage part of the bill. As you had a real estate agent (managing agent) looking after your property at the time when the water usage was not being paid by the tenant, it would have been their responsibility to either recoup this money from the tenant or organise with the water compony to send the usage part of the bill to the tenants. That is part of the service you were paying them for. You may need to check with Fair Trading in your state to find out who you should be going after for this money, the tenant or the real estate agent. In NSW you have 6 months after the lease has ended to take the tenants to tribunal to recoup owing money, I don't know how long it is after end your agreement with the real estate agent to pursue them. The case may be that you start with the tenant and if that doesn't work then try with the real estate agent. Of course you may want to contact your old tenants first to see if they are reasonable and agree to back pay the water usage (after you showing them copies of the water bills). The tribunal will ask if you have tried to mediate the matter first anyway. Then there is the matter of how much the water usage amounts to and whether it is worth chasing both the tenants and the real estate agent, paying the tribunal application fees and taking time off work to attend the tribunal.", "title": "" }, { "docid": "569642", "text": "Hi I am assuming you are doing this in the US? I run a social media / content marketing agency in the UK, Some of our very first clients were real estate agents, the idea we had was to market properties through Facebook using interior and exterior video shots to commercial music, This took off with some estate agents and not so much with others, My biggest piece of advice find a chain and start there that way you will get a hell of a lot of recognition by the smaller firms, You need to find a realistic price point for your clients that is measurable on the ROI and ultimately pays for your lifestyle. I started at £200 which is $257 dollars - arguably very underpriced but it gave me the opportunity to work with a cluster of people, I even went to the extreme of offering free work so I could get work for the portfolio! In terms of who to contact and how to find them.. enter Linkedin.com your new best friend - connect with real estate developers, buyers, owners you name it then informally introduce yourself and ask when they are free for a coffee. Post an article about why video and drone footage is the next big thing for real estate, don't be afraid to ask for the business at the end of the day you are providing cold hard value. I've always tried to get retainer deals with clients in the real estate sector but to achieve this you have to talk to the big boys and not independent firms. I could be wrong though I haven't done business with a lot of people in the states so definitely something to keep in mind. A good lot of this business idea is trial and error but I agree with it 100% just go and do basically, Hope this helps - I am happy to show you some of my work if you want to shoot me over a private message!", "title": "" }, { "docid": "487179", "text": "\"You are asking about a common, simple practice of holding the mortgage when selling a house you own outright. Typically called seller financing. Say I am 70 and wish to downsize. The money I sell my house for will likely be in the bank at today's awful rates. Now, a buyer likes my house, and has 20% down, but due to some medical bills for his deceased wife, he and his new wife are struggling to get financing. I offer to let them pay me as if I were the bank. We agree on the rate, I have a lien on the house just as a bank would, and my mortgage with them requires the usual fire, theft, vandalism insurance. When I die, my heirs will get the income, or the buyer can pay in full after I'm gone. In response to comment \"\"how do you do that? What's the paperwork?\"\" Fellow member @littleadv has often posted \"\"You need to hire a professional.\"\" Not because the top members here can't offer great, accurate advice. But because a small mistake on the part of the DIY attempt can be far more costly than the relative cost of a pro. In real estate (where I am an agent) you can skip the agent to hook up buyer/seller, but always use the pro for legal work, in this case a real estate attorney. I'd personally avoid the general family lawyer, going with the specialist here.\"", "title": "" }, { "docid": "209826", "text": "buying real estate is for people with sufficient financial resources to cover market downturns. Please read about the 2008 real estate market. Investing in real estate when you are a poor college student is a sure way to become a bankrupt college student. A single word answer to your question: No. Not reasonable. Your best investment is completing college with as little debt as possible and the most practical experience in the market area you are interested in entering.", "title": "" }, { "docid": "185246", "text": "There is no denying fact that they might still be in touch with the local real estate agents and the newspaper property advertisements to find a home that suits their needs, but they surely don't rely on them. The concept of online real estate agents is to win their trust and provide them reliable deal for selling their house.", "title": "" }, { "docid": "283480", "text": "\"The real estate agent industry is a cartel. They seek to keep fees high even as their services are becoming less and less necessary. To that end, traditional seller's agents will laugh at your attempt to negotiate their fee. They can do this quite simply because the industry is designed so the vast majority of people think of buyer's agents as \"\"free\"\" even when they are anything but free. That being said, the only way to do what you're trying to do is to find a buyer's agent who will rebate to you a portion of the commission they receive. It is extremely extremely unlikely you'll get a seller's agent to play ball especially once they know you're interested. You can check out redfin which connects people to RE agents that rebate commissions but the buyer's cut isn't that high. Your best bet, IMO, is to contact agents in your area before you go shopping to see what kind of rebate you can negotiate with them. A word of caution, if you look at a house without your own agent, instead asking the seller's agent to show the house they will claim procuring clause and you'll be sunk. In other words, once they claim procuring clause, you can't, later, go back and get a discount broker to get the commission to rebate to you.\"", "title": "" }, { "docid": "89964", "text": "\"It's extremely easy to get a rough valuation of your home. Just phone a real estate agent. Virtually any real estate agent will come and value your home free. Even if you say outright \"\"I'm not considering selling, I just want a valuation\"\" they will probably do it, because for them getting contacts of people who might one day want to sell their home is all-important. Even if a few turn you down, some will do it. You might say that an agent isn't going to be as accurate as an appraiser, and you are right. There is also an expectation that they will evaluate higher than the real value, to persuaade you to sell. That probably isn't a big issue, and it's something you can compensate for. And even an appraiser is going to be based somewhat on speculation. You might try to do this calculation yourself, but an agent has access to the actual sale prices of nearby houses - you can't get that information. You only have access to the asking prices. And did I mention they will do it for free?\"", "title": "" }, { "docid": "441536", "text": "When clearing funds from the sale of a home the following usually happens (USA): The left over amount is what you get. Your real estate agent should be able to go over all of that with you. If they haven't then you need to get a better real estate agent. Assuming you haven't listed the house on the market yet then you should probably start by finding out what the pay off amount is on your existing home (call your mortgage company), then look at the prices of recently sold homes in your neighborhood for a comparable house (same style/square footage/amenities) to see what it sold for. Now you will know exactly what all those costs are prior to sitting down and signing the paperwork for the sale during the closing proceedings. If for some reason the amount is less than what you owe on it then the mortgage company would have to be involved for you to even sell it. If the real estate market in your area is somewhat normal, you bought the house on a standard fixed rate mortgage, you've been paying faithfully these past 17 years, you haven't gotten a home equity line of credit (HELOC) loan (or otherwise cashed out of your equity at any point), you've kept up the maintenance of the place and there are no liens against the property (ie: unpaid taxes, lawsuits, etc) then it is highly likely you will get money from the sale of the house. However we (internet people) don't know any of those details; so talk to a good real estate agent.", "title": "" }, { "docid": "481747", "text": "From your profile, I see you are in Israel. The process is probably different from in the US. In the US, an agent is usually happy to work with a buyer. After all, When I list a house, there are potential buyers all over my state and elsewhere. The best thing you can do is first, have your financing in order. A bank will be able to tell you how much you can afford and how much they'll lend you. If you approach an agent and tell them the exact range of price, area you're interested in, and other specifics such as number of bedrooms, etc, that agent should be happy to find houses to fit your request. Obviously, an agent listing million dollar homes, busy with those all day, is not going to want to handle a buyer looking for a $200K home. But in the end, the real estate agents aren't all listing high end, and someone is moving the smaller houses as well. Often, an office will have a call center where agents who are less busy will answer the phone hoping to get a client that will bring a sale. That's one way to go. The other is word of mouth. Just ask others who you work with or socialize with if they know a good agent. In my case, I'd be happy to get such a referral.", "title": "" }, { "docid": "581098", "text": "Many real estate agents will assist with an apartment hunt, for a suitable fee. In a hot market that may be worth the money. Then again, my best finds were always through co-workers, after the first two.", "title": "" }, { "docid": "587288", "text": "Database For Business connects its users to Dubai real estate information, analysis, data, news and opportunities, you should select the right business directory in Dubai, that's capable for better service of real estate database. We have a more database service such as mobile database, business database, email marketing database and we provide new technology service with UAE real estate database. It is a trustable place for you in Dubai, we have different service of database in lowest price which is essential for your real estate business. The Database For Business is a collaboration of real estate agents and always help you to keep secure data of real estate business. We offer an extensive database of Dubai properties to our clients.", "title": "" }, { "docid": "348511", "text": "\"I hope you're not blaming the banks for the housing price inflation. It's called supply and demand, and is mostly caused by people, possibly like you, who have unreasonable expectations about the future value of real estate, and thought it would keep rising unrealistically forever. The bank's \"\"crime\"\" was to lend money recklessly, to people who could not really afford it. The buyer's \"\"crime\"\" was to buy a home they could not afford with the expectations that it would go up in price and they could either flip it or refinance. The real \"\"criminals\"\" might be the real estate agents who convinced the buyers they could afford it, and helped them find an avenue to get the money. There were (are?) a lot of unscrupulous, or simply bad, real estate agents out there. But they, too, were naive enough to think houses would continue to rise. tl;dr. We are all to blame. Calling owners \"\"slumlords\"\" and blaming them and the banks for your misfortune will only hurt you and make you forever the victim.\"", "title": "" }, { "docid": "24591", "text": "\"You said: \"\"should I make a side contract with the realtor to pay me the commission at closing?\"\" I would imagine that in most (if not all) states, that is illegal. This is because selling real estate is an activity that requires passing an exam on real estate laws and obtaining a state-issued license. You are not \"\"bringing a buyer\"\" because you are not an agent. If you decide to go directly to the Realtor that has the listing, there is a possibility that the agent might agree to lowering their commission in order to make the sale. However, the agent is entitled to both sides of the commission because they bear all the administrative and marketing costs of the transaction. The listing agent might choose to enter into a \"\"dual agency\"\" agreement where they would have to fairly represent both sides, but they cannot reveal information that would be helpful to you as a buyer (e.g., why the seller is choosing to sell, other material facts about the property that are not public knowledge, etc.). If there is no written \"\"dual agency\"\" agreement, then the listing agent ONLY represents the seller. In either scenario, you lose the benefit of a full fiduciary relationship with an agent. So if you choose to deal directly with the listing agent, you are making one of the biggest purchases of your lifetime WITHOUT the benefit of professional representation. Do you really want that? Put another way: would you use your spouse's attorney in a divorce so that you could save money?\"", "title": "" }, { "docid": "217242", "text": "You could look into an index fund or ETF that invests primarily in Real Estate Investment Trusts (REIT's). An REIT is any corporation, trust or association that acts as an investment agent specializing in real estate and real estate mortgages Many investment firms offer an index fund or ETF like this. For example, Vanguard and Fidelity have funds that invest primarily in real estate markets. You could also invest in a home construction ETF, like iShares' ITB, which invests in companies related to home construction. This ETF includes more companies than just REITs, so for example, Home Depot is included.", "title": "" }, { "docid": "349380", "text": "Since you are leaving the country, get it sold by a real estate agent. If you choose to lower the price and get it done quickly, or if you choose to wait for a fair value, the key here is to get many independent referrals (like a dozen) so you agent is trustworthy. I don't think you need to sign over power of attorney as fax machines are pretty reliable these days. I won't matter if you live 50 miles or 5000 miles away. Renting it is not a great option because you can't easily follow up from another country. Don't sell it to the rock bottom places. Either you don't need the money and you can afford to you wait, or you need the money and it would be best to wait.", "title": "" }, { "docid": "40049", "text": "Having just gone through this process as a buyer via broker in Israel, here are my thoughts: Tl;dr: An incentive such as you are suggesting would not be particularly helpful. In this case, your best option is to spend your efforts shopping for a broker that you can trust. The rest: Your main concern is that the broker will find you a place at the top of your budget and will not negotiate aggressively. The main person responsible for negotiation is YOU. You are paying for the property, and you are putting in bids: not your agent. The agent should advise you, but in the end should pass along your bids directly. The real problem is that you, as the buyer, generally do not have as close a feel for the pulse of the market as the broker, who should be quite aware of recent closings in the neighborhood. Therefore, there are a few things that you can do to help arm yourself: At the end of the day, if you have decided to use a broker, you are making a large financial commitment to hire someone to find you the best place, and therefore it may be more important at this point to spend your efforts shopping around for the best broker, rather than trying to figure out how to outsmart her. You are correct: buyers' agents DO have incentives to sell you on places that may not be right or good for you. For example: Although your scheme may help a bit with the first concern, it will not help at all with the other two, which I assume to be much more likely problems in any event. Instead, find recommendations for brokers from others. Have the broker show you a few properties and put in some low bids to get a feel for how she handles them. Discuss the properties together and try to assess if they really have your interests in mind. You are paying a lot for their service, and you should make sure, as much as possible, that they really are working honestly and in your best interest. A good broker who knows his market and is trying to help you can be a great asset in the opaque, cutthroat real estate market. הבל הבלים, הכל הבל. סוף דבר הכל נשמע, את האלוהים יירא ואת מצוותיו שמור כי זה כל האדם. Good luck!", "title": "" }, { "docid": "387908", "text": "For a real estate transaction there are multiple stages: From the sellers viewpoint: From the buyers viewpoint: If both parties are comfortable skipping some of the steps the role of the agent can be minimized. How will a fair price be determined? Some realism might be needed, to make sure that the loan appraisal will not be a problem. Will an inspection still be needed? What warranty will exist if the A/C dies this summer? If you still want help from an agent one should be able to help for far less than the normal commission. The seller normally interviews three agents before selecting one, do the same in this situation. Ask how much they would charge for a sale between friends. They can complete their task in just a couple of hours. If the home inspection comes back relatively clean, the transaction should be very easy. The paperwork is the biggest hurdle. You should jointly identify a local settlement company. They will be the ones actually filing the paperwork. They have lawyers. They will check the county records office for existing liens, plats, mortgages and address all the issues. They can send the proper paperwork to the existing mortgage companies and arrange for mortgage insurance. The cost will be the same regardless of the presence of real estate agents and other lawyers. When they say a lawyer is required, it is only because of the paperwork.", "title": "" }, { "docid": "120061", "text": "\"First piece of advice: fire your agent. A pushy agent is a bad agent. From what you've told us, he's actually given you poor advice regarding mortgage interest rates. Rates are already at historic lows. That and the precarious state of the world economy mean that further rate cuts are more likely in the near term. Second piece of advice: While more information on the real estate market you're in would help, going in at asking price is rarely a good idea. Sale prices from \"\"the last few years\"\" are not relevant to what you should pay, because the last few years include a financial crisis caused in large part by the bursting of a housing bubble. They could be even less relevant depending on your location because of a spike in foreclosures in certain areas of the U.S. There was already a ton of housing inventory before, so an increase due to foreclosures is going to depress prices further. Now that banks are finally practicing the due diligence they should have been all along, your ability to be pre-approved for large mortgage amount puts you in a strong position. Use a tool like Zillow or Redfin to see what properties in that area have sold for over the past six months. You should also be able to see a history of what prices the particular property you're interested in has been offered and/or sold at in the past. Also check and see how long the particular property you're interested in has been on the market. If it's been on the market more than 60-90 days, it's priced too high.\"", "title": "" }, { "docid": "160087", "text": "Selling a home by yourself, without an expensive real estate broker, is easier than most people think, but it will take some work on your part. You will be doing a lot of things that a real estate agent might normally do.", "title": "" }, { "docid": "389333", "text": "If you are searching for a country home or a new homes in Renton WA just a few hours from Washington, 1000 First Street is a wise choice. Datta Homes is one of the top real estate agent, providing exceptional real estate service in Washington, based on the highest standard of ethics.", "title": "" }, { "docid": "336441", "text": "You decide whether the improvements will result in a net higher price. You also need to figure on how long the house will be on the market and the cost of carrying the home, unoccupied. Some people would prefer the quickest sale. Others would wait to get the highest price. If you sell to a known buyer, you avoid using a real estate agent. If you plan to sell on your own and avoid the agent, there's a bit of effort dealing with the public, especially those who just want to look at houses with no real interest in buying. (As an agent, I can tell you, there's nothing like talking for nearly an hour, and then figuring out these people are from 1/2 mile away, but just attend every open house in the area.)", "title": "" }, { "docid": "296591", "text": "Let's think like a real estate developer. First you need to check with the zoning commission the restrictions for the area. Let's say that the plot is actually suitable for 10 homes. You buy the land. You also need to finance the build itself. If you don't have enough cash you need to acquire financing from banks and perhaps from other sources as well, because banks won't loan you the entire amount. Next you need to divide the plot into 10 pieces, making sure that each piece has driveway access to the street and plan access to utilities (water/sewer/electricity/broadband/phone lines). Plan the size and position of each house. Get building approval. This is a process that can take some time, especially if they have follow-up questions. Get a builder to build the houses, including ground work and preparation for utilities. Get approval for the finished houses. A building inspector will check that the houses follow the permission and all laws and regulations that apply. This step can entail time and added cost. Get a real estate agent to sell the new homes. Often, the selling process starts in the planning phase and early buyers are able to influence both the layout of the house and the finish. Your cost estimate included a profit of 140k for each house. From that a builder needs to subtract financing costs, real estate agent costs, any costs that you forgot to factor in, budget overdrafts, contingency costs, and salaries for your staff and yourself. I estimate the project time to 1.5-2 years. So, we have an $8M project with a gross profit of $1.4M (not including all costs). Net profit probably just a few hundred thousand. Or less. Real estate developers with local knowledge would be able to make a much more accurate estimate on both time and cost. My guess is that they have, and since the plot hasn't sold in a while, either the price is at the upper end of what makes a profitable project or there are other restrictions that limit the number/size of homes that can be built on it.", "title": "" }, { "docid": "53092", "text": "First, let me say that you have to take everything your agent says with a grain of salt. Freakonomics had a great article that discussed the math behind the motivation of the real estate agent. It described the home seller, trying to get, say $400K. On a 6% commission, the $24K is destined to be split between seller realtor office and buyer's realtor's office. The selling agent gets $6,000 (or so) in the end. As a seller, if I settle for $380K, my realtor is only out $300, netting $5700. But $20K lower sale price, and I just lost nearly $19K after commission is paid. The agent would have the natural goal of volume, not extracting the last dollar from the buyer. Gaining back the last $20K to the seller will cost the realtor far more than $300 in her time, keeping the house on the market and waiting for the better offer. Sellers might use down payment as one way to estimate the probability of the financing falling through, but it's a rough estimate at best because, in the case of bank financing, the bank needs the same time to run through the paperwork for a 3% down or a 20% down. It's just as easy for the buyer to qualify or not qualify for one loan or the other. There are young couples with great incomes and no debt, who blow away the required ratios for proposed debt to income, but haven't saved up the otherwise huge 20% downpayment. Then there are those who have saved for years, even having 30% to put down, but their income is still not going to qualify them. The offer will be contingent on the financing, regardless. It will show that you are putting $XX dollars as a downpayment, and the final transaction is contingent on your bank approving you.", "title": "" } ]
PLAIN-104	A Low Methionine Diet May Help Starve Cancer Cells	[ { "docid": "MED-3715", "text": "INTRODUCTION: Questions have recently arisen in the popular press about the association between specific sexual behaviors, namely, fellatio and cunnilingus, with head and neck cancers. Although there has been an overall decline in the incidence of head and neck cancers over the past 25 years, there has been a shift in the distribution of these cancers toward a particular type known as oral squamous cell carcinomas (OSCCs), and a younger demographic. These particular cancers, OSCCs, have been shown to be associated with the human papillomavirus (HPV). Several researchers have suggested that this shift in the epidemiology of head and neck cancers might be attributable to changing sexual practices. While this speculation has caught on in the popular press, there are several interesting contradictions in the existing evidence that suggest this conclusion might be premature and overreached. AIM: The intent of this article is to help clarify the issues so that sexual medicine professionals can give accurate and up-to-date information to their patients. MAIN OUTCOME MEASURES: This is a review article; no outcome data are reported. This is a review article; no measures were collected. METHODS: Pubmed search on HPV, oral sex, oral cancers, and OSCCs. RESULTS: One hundred ninety-six articles on HPV were found; 63 articles on oral sex, 55 on oral cancer, and 5 articles on OSCCs were identified as relevant. CONCLUSIONS: HPV infections occur commonly and are usually cleared within 18 months, thus HPV infection should not be a cause for concern among monogamous couples with a rich and varied sex life as long as the sexual system remains closed and other immune compromising factors are not present. HPV becomes a concern in the context of immune system compromise and infection persistence. Factors contributing to immune system compromise, HPV persistence, and oncogenesis are reviewed. © 2012 International Society for Sexual Medicine.", "title": "Is oral sex really a dangerous carcinogen? Let's take a closer look." }, { "docid": "MED-5327", "text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.", "title": "The association between dietary patterns and mental health in early adolescence." }, { "docid": "MED-3282", "text": "BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.", "title": "Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment." }, { "docid": "MED-3732", "text": "Background Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence. Nevertheless, the technique is time-consuming, technically demanding and associated with a high complication rate. To reduce the risk of complications, different devices and technical advances have been proposed with conflicting results and, still, ESD en bloc resections of huge lesions are associated with increased complications. Case Presentation We successfully used a combined ESD/EMR technique for huge rectal laterally spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the lesion followed by piecemeal resection (2-3 pieces) of the central part of the tumour. In all three patients we obtained the complete dissection of the polyp and the complete histological evaluation in absence of complications and recurrence at 6 months' follow up. Conclusions In the treatment of rectal LSTs, the combined treatment - ESD/EMR resection may be considered a suitable therapeutic option, indicated in selected cases as an alternative to surgery, in which the two techniques are neither reliable nor safe separately. However, to confirm our results, larger trials with longer follow up are required together with improvement of the technique and of the technical devices.", "title": "Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection" }, { "docid": "MED-3549", "text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.", "title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention." }, { "docid": "MED-4116", "text": "The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.", "title": "The flip side of immune surveillance: immune dependency." }, { "docid": "MED-5341", "text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.", "title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro." }, { "docid": "MED-3731", "text": "Esophageal cancer is highly aggressive and is a common cancer both worldwide and in the US. In the past two decades, the incidence and mortality of esophageal cancer in the US have both increased, where as the incidence and mortality of other cancers have decreased. Although esophageal squamous cell carcinoma and esophageal adenocarcinoma differ in their histology and epidemiologic distribution, some of their risk factors (e.g. dietary deficiencies and tobacco) and underlying mechanisms of carcinogenesis are the same. Intensive research into risk factors combined with the ability to identify precursor lesions (e.g.squamous dysplasia in esophageal squamous cell carcinoma and Barrett's esophagus in esophageal adenocarcinoma) has paved the way for studies of chemoprevention for esophageal cancer, some of which have shown promising results.", "title": "Esophageal cancer: epidemiology, pathogenesis and prevention." }, { "docid": "MED-3274", "text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.", "title": "Olfactory detection of human bladder cancer by dogs: proof of principle study" }, { "docid": "MED-4891", "text": "The current annual incidence of sudden cardiac death in the US is likely to be in the range of 180–250,000 per year. Coinciding with the decreased mortality from coronary artery disease, there is evidence pointing toward a significant decrease in rates of sudden cardiac death in the US during the second half of the twentieth century. However the alarming rise in prevalence of obesity and diabetes in the first decade of the new millennium both in the US and worldwide, would indicate that this favorable trend is unlikely to persist. We are likely to witness a resurgence of coronary artery disease and heart failure, as a result of which sudden cardiac death will have to be confronted as a shared and indiscriminate, worldwide public health problem. There is also increasing recognition of the fact that discovery of meaningful and relevant risk stratification and prevention methodologies will require careful prospective community-wide analyses, with access to large archives of DNA, serum and tissue that link with well-phenotyped databases. The purpose of this review is to summarize current knowledge of sudden cardiac death epidemiology. We will discuss the significance and strengths of community-wide evaluations of sudden cardiac death, summarize recent observations from such studies, and finally highlight specific potential predictors that warrant further evaluation as determinants of sudden cardiac death in the general population.", "title": "Epidemiology of Sudden Cardiac Death: Clinical and Research Implications" }, { "docid": "MED-3728", "text": "On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.", "title": "Strawberry fields forever?" }, { "docid": "MED-3276", "text": "Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension." }, { "docid": "MED-3726", "text": "Cancer is the second leading cause of death worldwide. Therefore, the fight against cancer is one of the most important areas of research in medicine, and one that possibly contributes to the increased interest in chemoprevention as an alternative approach to the control of cancer. Cancer prevention by nutraceuticals present in fruits and vegetables has received considerable attention because of their low cost and wide safety margin. A substantial amount of evidence from human, animal, and cell culture studies has shown cancer chemopreventive effects from these natural products. However, single-agent intervention has failed to produce the expected outcome in clinical trials; therefore, combinations of nutraceuticals are gaining increasing popularity. Thus, combinations of nutraceuticals that mimic real-life situations and are competent in targeting multiple targets with very little or virtually no toxicity are needed. In this review, we summarize the results of those studies that report combinatorial cancer chemopreventive action of various nutraceuticals and their combinations with anticancer drugs. © 2011 New York Academy of Sciences.", "title": "Combinatorial strategies employing nutraceuticals for cancer development." }, { "docid": "MED-5339", "text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.", "title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat." }, { "docid": "MED-3729", "text": "Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Role of antioxidants in cancer therapy." }, { "docid": "MED-3724", "text": "Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.", "title": "Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells." }, { "docid": "MED-4609", "text": "Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.", "title": "The beriberi analogy to myocardial infarction." }, { "docid": "MED-4886", "text": "OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.", "title": "Clinical events in prostate cancer lifestyle trial: results from two years of follow-up." }, { "docid": "MED-4890", "text": "Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.", "title": "Effect of diet and exercise intervention on the growth of prostate epithelial cells." }, { "docid": "MED-3555", "text": "A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.", "title": "Phytochemicals and cancer risk: a review of the epidemiological evidence." }, { "docid": "MED-3714", "text": "The present study was conducted to determine differences in antioxidant levels of fresh, frozen, and freeze-dried strawberries, and strawberry jam. Hydrophilic antioxidant activity (HAA) and lipophilic antioxidant activity (LAA) were measured using the ABTS/H₂O₂/HRP decoloration method. HAA and LAA were then summed to calculate the total antioxidant activity (TAA). Mean differences in HAA and LAA were analyzed using one-way analysis of variance and Dunnett's T3 pairwise comparisons. The mean TAA for freeze-dried strawberries based on an 'as consumed' weight (95% confidence interval [CI]: 29.58, 30.58) was significantly higher than for fresh (95% CI: 3.18, 3.66), frozen (95% CI: 2.58, 2.79), and jam (95% CI: 1.10, 1.22). The mean TAA based on dry weight for fresh strawberries (95% CI: 40.48, 46.67) was significantly higher than for freeze-dried (95% CI: 29.58, 30.58), frozen (95% CI: 24.62, 26.59), and jam (95% CI: 1.48, 1.64). Results agree with previous studies reporting that strawberries are a valuable source of antioxidants for consumers.", "title": "Differences in antioxidant levels of fresh, frozen and freeze-dried strawberries and strawberry jam." }, { "docid": "MED-3552", "text": "The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.", "title": "Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis." }, { "docid": "MED-3722", "text": "BACKGROUND: The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. PATIENTS AND METHODS: We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. RESULTS: We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. CONCLUSION: Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.", "title": "Dietary patterns and the risk of esophageal cancer." }, { "docid": "MED-3271", "text": "Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.", "title": "Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?" }, { "docid": "MED-3275", "text": "In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.", "title": "The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture" }, { "docid": "MED-3281", "text": "INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.", "title": "Targeting methionine auxotrophy in cancer: discovery & exploration." }, { "docid": "MED-5322", "text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.", "title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting." }, { "docid": "MED-5324", "text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.", "title": "Effects of a high-fat meal on pulmonary function in healthy subjects." }, { "docid": "MED-5335", "text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.", "title": "Does a vegan diet reduce risk for Parkinson's disease?" }, { "docid": "MED-4612", "text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.", "title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity." }, { "docid": "MED-3721", "text": "Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.", "title": "Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions" }, { "docid": "MED-4888", "text": "Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.", "title": "Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention" }, { "docid": "MED-4117", "text": "Breast cancer is a complex disease. Its aetiology is multifactorial, its period of development can span decades, and its clinical course is highly variable. Evaluation of the role of the immune response in either the development or control of breast cancer is also complex. Nevertheless, there is substantial information that in this disease, the immune response is not a host defence reaction and may even serve to facilitate cancer development. This evidence comes from a variety of sources including clinical-pathological investigations in women that show a correlation between the intensity of lymphocytic infiltration into the tumour mass with poor prognosis, studies in breast cancer patients that demonstrate a similar correlation between delayed hypersensitivity reactivity or in vitro assays of immune reactivity to tumour cell membranes or non-specific antigens and poor prognosis, and analyses of cancer incidence in chronically immunosuppressed, kidney transplant recipients who develop an unexpectedly low incidence of breast cancer. The overall conclusions from these human studies are corroborated by observations in mouse mammary tumour models that also demonstrate immune enhancement of breast cell proliferation in vitro and of breast cancer development in vivo. Potential mechanisms for these effects include production, by inflammatory cell infiltrates, of direct or indirect modulators of breast cell growth, e.g. cytokines, peptide or steroid hormones, enzymes involved in steroid metabolism, as well as of antibodies to growth factors or their receptors. These immune facilitatory mechanisms must be overcome if immune-based therapies are to be applied successfully in breast cancer.", "title": "Immunological enhancement of breast cancer." }, { "docid": "MED-5342", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-3717", "text": "We briefly highlight the growing body of recent evidence linking unprotected oral sex with the development of some types of head and neck cancer in younger patients. These tumours appear to be increasing in incidence although the development of more sensitive methods of HPV detection may be a confounding factor.", "title": "Oral sex, cancer and death: sexually transmitted cancers" }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-3280", "text": "Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.", "title": "Methionine dependency and cancer treatment." }, { "docid": "MED-3548", "text": "Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.", "title": "Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities." }, { "docid": "MED-3553", "text": "Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway." }, { "docid": "MED-5330", "text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.", "title": "Effect of a single high-fat meal on endothelial function in healthy subjects." }, { "docid": "MED-3730", "text": "Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting. ©2011 AACR.", "title": "Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus." }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-5325", "text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.", "title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)" }, { "docid": "MED-5328", "text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.", "title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2" }, { "docid": "MED-3719", "text": "Purpose The objective of this study was to formulate and evaluate freeze-dried black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants for sustained delivery of chemopreventive FBR anthocyanins (cyanidin-3-sambubioside (CS), cyanidin-3-glucoside (CG) and cyanidin-3-rutinoside (CR)). Methods Identification and quantitation of CS, CG, and CR in RE was performed by mass spectroscopy and HPLC. RE:triacetyl-β-cyclodextrin (TA-β-CD) inclusion complex (IC) was prepared by a kneading method and characterized by X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR) and UV-visible spectroscopy. RE or RE:TA-β-CD IC-loaded PLGA or PLA implants were prepared by a solvent extrusion method. In vitro and in vivo controlled release studies were conducted in phosphate-buffered saline Tween-80 (pH 7.4, 37°C) and after subcutaneous administration in male Sprague-Dawley rats, respectively. Anthocyanins were quantified by HPLC at 520 nm. Results The content of CS, CG, and CR in RE was 0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of anthocyanins in solution was determined to be pH-dependent, and their degradation rate increased with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical implants loaded with 5 or 10 wt% RE exhibited a high initial burst and short release duration of anthocyanins (35–52 and 80–100% CG + CR release after 1 and 14 days, respectively). The cause for rapid anthocyanins release was linked to higher polymer water uptake and porosity associated with the high osmolytic components of large non-anthocyanin fraction of RE. XRD, 1H NMR and UV-visible spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed an IC with TA-β-CD, decreasing the hydrophilicity of RE. Formation of an IC with hydrophobic carrier, TA-β-CD, provided better in vitro/in vivo sustained release of FBR anthocyanins (16–24 and 97–99% CG + CR release, respectively, after 1 and 28 days from 20 wt% RE:TA-β-CD IC/PLA implants) over 1 month, owing to reduced polymer water uptake and porosity. Conclusion PLA injectable millicylindrical implants loaded with RE:TA-β-CD IC are optimal dosage forms for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins.", "title": "Formulation and In Vitro-In Vivo Evaluation of Black Raspberry Extract-Loaded PLGA/PLA Injectable Millicylindrical Implants for Sustained Delivery of Chemopreventive Anthocyanins" }, { "docid": "MED-5323", "text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.", "title": "Endocrine-disrupting chemicals and obesity development in humans: a review." }, { "docid": "MED-5331", "text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.", "title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland." }, { "docid": "MED-5340", "text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.", "title": "Renal function parameters of Thai vegans compared with non-vegans." }, { "docid": "MED-3270", "text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.", "title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals." }, { "docid": "MED-3272", "text": "Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.", "title": "Colorectal cancer screening with odour material by canine scent detection" }, { "docid": "MED-3277", "text": "Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.", "title": "Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture." }, { "docid": "MED-3278", "text": "Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.", "title": "Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening" }, { "docid": "MED-3716", "text": "Purpose The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene – associated chromosomal loci have been associated with a higher risk for oral IEN progression to oral squamous cell carcinoma. Previously, our laboratories have shown that FBRs are well tolerated and possess potent antioxidant, apoptotic, and differentiation-inducing properties. Experimental Design Each participant with IEN served as their own internal control. Before treatment, all lesions were photographed, and lesional tissue was hemisected to obtain a pretreatment diagnosis and baseline biochemical and molecular variables. Gel dosing (0.5 g applied four times daily for 6 weeks) was initiated 1 week after the initial biopsy. Genomic DNA was isolated from laser-captured basilar and suprabasilar surface epithelial cells followed by PCR amplification using primer sets that targeted known and presumed tumor suppressor gene loci associated with INK4a/ARF, p53, and FHIT. Allelic imbalance was determined by sequence analysis using normal participant tissues to establish microsatellite marker peak patterns and allele sizes. Results Confirming earlier phase I data, none of the 27 participants developed FBR gel – associated toxicities. Furthermore, our results show histologic regression in a subset of patients as well as statistically significant reduction in LOH at tumor suppressor gene – associated loci. Conclusions These preliminary data suggest that further evaluation of berry gels for oral IEN chemoprevention is warranted.", "title": "Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions" }, { "docid": "MED-5333", "text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.", "title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis." }, { "docid": "MED-4617", "text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.", "title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States" }, { "docid": "MED-3720", "text": "Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear. In this study, we found that 2 major chemopreventive components of black raspberries, ferulic acid and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica column chromatography of the organic extract of freeze-dried black raspberries inhibit the growth of premalignant and malignant but not normal human oral epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and ellagic acid inhibited the growth of normal as well as premalignant and malignant human oral cell lines. We investigated the molecular mechanisms by which ferulic acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth of premalignant and malignant oral cells using flow cytometry and Western blotting of cell cycle regulatory proteins. There was no discernable change in the cell cycle distribution following treatment of cells with the RO-ET fraction. Premalignant and malignant cells redistributed to the G2/M phase of the cell cycle following incubation with ferulic acid. beta-sitosterol treated premalignant and malignant cells accumulated in the G0/G1 and G2/M phases, respectively. The RO-ET fraction reduced the levels of cyclin A and cell division cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1 in the malignant cell line. Ferulic acid treatment led to increased levels of cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2 while increasing p21waf1/cip1 in both the premalignant and malignant cell lines. These results show for the first time that the growth inhibitory effects of black raspberries on premalignant and malignant human oral cells may reside in specific components that target aberrant signaling pathways regulating cell cycle progression.", "title": "Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries." }, { "docid": "MED-3744", "text": "Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.", "title": "Antioxidant and antiproliferative activities of common fruits." }, { "docid": "MED-4887", "text": "Cardiovascular symptom relief is a major indicator for revascularization procedures. To examine the effects of intensive lifestyle modification on symptom relief, we investigated changes in angina pectoris, coronary risk factors, quality of life, and lifestyle behaviors in patients with stable coronary artery disease enrolled in the multisite cardiac lifestyle intervention program, an ongoing health insurance-covered lifestyle intervention conducted at 22 sites in the united states. Patients with coronary artery disease (nonsmokers; 757 men, 395 women; mean age 61 years) were asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). At baseline, 108 patients (43% women) reported mild angina and 174 patients (37% women) reported limiting angina. By 12 weeks, 74% of these patients were angina free, and an additional 9% moved from limiting to mild angina. This improvement in angina was significant for patients with mild and limiting angina at baseline regardless of gender (p <0.01). Significant improvements in cardiac risk factors, quality of life, and lifestyle behaviors were observed, and patients with angina who became angina free by 12 weeks showed the greatest improvements in exercise capacity, depression, and health-related quality of life (p <0.05). In conclusion, the observed improvements in angina in patients making intensive lifestyle changes could drastically reduce their need for revascularization procedures.", "title": "Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program." }, { "docid": "MED-5332", "text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.", "title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age." }, { "docid": "MED-5334", "text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.", "title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study." }, { "docid": "MED-3554", "text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.", "title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer." }, { "docid": "MED-5326", "text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?" }, { "docid": "MED-3279", "text": "Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.", "title": "Chitin synthesis and degradation as targets for pesticide action." }, { "docid": "MED-3283", "text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.", "title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..." }, { "docid": "MED-3550", "text": "Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.", "title": "Tumor Angiogenesis as a Target for Dietary Cancer Prevention" }, { "docid": "MED-4220", "text": "OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.", "title": "Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)." }, { "docid": "MED-5338", "text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.", "title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease" }, { "docid": "MED-4613", "text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.", "title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition." }, { "docid": "MED-3551", "text": "Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer." }, { "docid": "MED-3718", "text": "The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.", "title": "American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices ..." }, { "docid": "MED-3723", "text": "Epidemiological studies investigating the association between dietary intake and oesophageal cancer have mostly focused on nutrients and food groups instead of dietary patterns. We conducted a population-based case-control study, which included 365 oesophageal adenocarcinoma (OAC), 426 oesophagogastric junction adenocarcinoma (OGJAC) and 303 oesophageal squamous cell carcinoma (OSCC) cases, with frequency matched on age, sex and geographical location to 1580 controls. Data on demographic, lifestyle and dietary factors were collected using self-administered questionnaires. We used principal component analysis to derive three dietary patterns: 'meat and fat', 'pasta and pizza' and 'fruit and vegetable', and unconditional logistic regression models to estimate risks of OAC, OGJAC and OSCC associated with quartiles (Q) of dietary pattern scores. A high score on the meat-and-fat pattern was associated with increased risk of all three cancers: multivariable-adjusted OR 2·12 (95 % CI 1·30, 3·46) for OAC; 1·88 (95% CI 1·21, 2·94) for OGJAC; 2·84 (95% CI 1·67, 4·83) for OSCC (P-trend <0·01 for all three cancers). A high score on the pasta-and-pizza pattern was inversely associated with OSCC risk (OR 0·58, 95 % CI 0·36, 0·96, P for trend=0·009); and a high score on the fruit-and-vegetable pattern was associated with a borderline significant decreased risk of OGJAC (OR for Q4 v. Q1 0·66, 95% CI 0·42, 1·04, P=0·07) and significantly decreased risk of OSCC (OR 0·41, 95% CI 0·24, 0·70, P for trend=0·002). High-fat dairy foods appeared to play a dominant role in the association between the meat-and-fat pattern and risk of OAC and OGJAC. Further investigation in prospective studies is needed to confirm these findings.", "title": "Dietary patterns and risk of oesophageal cancers: a population-based case-control study." }, { "docid": "MED-5329", "text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.", "title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet." }, { "docid": "MED-4481", "text": "The aim of this study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data was collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients, and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (OR) and 95% confidence intervals (95%CI), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR=3.54; 95%CI=1.32–9.46) and EAC (OR=5.44; 95%CI=2.08–14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR=2.79; 95%CI=1.11–7.04; OR=2.41; 95%CI=1.14–5.08, respectively) and monounsaturated fat intake (OR=2.63; 95%CI=1.01–6.86; OR=5.35; 95%CI=2.14–13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR=3.15; 95%CI=1.38–7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR=4.67; 95%CI=1.71–12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies, investigating the association between dietary fat and food sources of fat are needed to confirm these results.", "title": "Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma" }, { "docid": "MED-3273", "text": "Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.", "title": "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy." } ]	[ { "docid": "MED-1333", "text": "New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.", "title": "Insulin secretion as a determinant of pancreatic cancer risk." }, { "docid": "MED-2578", "text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.", "title": "Dietary suppression of colonic cancer. Fiber or phytate?" }, { "docid": "MED-1305", "text": "This viewpoint aims to 1) review the available scientific literature on the relationship between whole grain consumption and body weight regulation; 2) evaluate the potential mechanisms whereby whole grain intake may help reduce overweight and 3) try to understand why epidemiological studies and clinical trials provide diverging results on this topic. All the prospective epidemiological studies demonstrate that a higher intake of whole grains is associated with lower BMI and body weight gain. However, these results do not clarify whether whole grain consumption is simply a marker of a healthier lifestyle or a factor favoring \"per se\" lower body weight. Habitual whole grain consumption seems to cause lower body weight by multiple mechanisms such as lower energy density of whole grain based products, lower glycemic index, fermentation of non digestible carbohydrates (satiety signals) and finally by modulating intestinal microflora. In contrast with epidemiological evidence, the results of few clinical trials do not confirm that a whole grain low-calorie diet is more effective in reducing body weight than a refined cereal diet, but their results may have been affected by small sample size or short duration of the intervention. Therefore, further intervention studies with adequate methodology are needed to clarify this question. For the time being, whole grain consumption can be recommended as one of the features of the diet that may help control body weight but also because is associated with a lower risk to develop type 2 diabetes, cardiovascular diseases and cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Whole grain intake in relation to body weight: from epidemiological evidence to clinical trials." }, { "docid": "MED-2044", "text": "Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?" }, { "docid": "MED-4239", "text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.", "title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro." }, { "docid": "MED-3785", "text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.", "title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites." }, { "docid": "MED-2434", "text": "The specific role of dietary fat in breast cancer progression is unclear, although a low-fat diet was associated with decreased recurrence of estrogen receptor alpha negative (ER(-)) breast cancer. ER(-) basal-like MDA-MB-231 and MDA-MB-436 breast cancer cell lines contained a greater number of cytoplasmic lipid droplets compared to luminal ER(+) MCF-7 cells. Therefore, we studied lipid storage functions in these cells. Both triacylglycerol and cholesteryl ester (CE) concentrations were higher in the ER(-) cells, but the ability to synthesize CE distinguished the two types of breast cancer cells. Higher baseline, oleic acid- and LDL-stimulated CE concentrations were found in ER(-) compared to ER(+) cells. The differences corresponded to greater mRNA and protein levels of acyl-CoA:cholesterol acyltransferase 1 (ACAT1), higher ACAT activity, higher caveolin-1 protein levels, greater LDL uptake, and lower de novo cholesterol synthesis in ER(-) cells. Human LDL stimulated proliferation of ER(-) MDA-MB-231 cells, but had little effect on proliferation of ER(+) MCF-7 cells. The functional significance of these findings was demonstrated by the observation that the ACAT inhibitor CP-113,818 reduced proliferation of breast cancer cells, and specifically reduced LDL-induced proliferation of ER(-) cells. Taken together, our studies show that a greater ability to take up, store and utilize exogenous cholesterol confers a proliferative advantage to basal-like ER(-) breast cancer cells. Differences in lipid uptake and storage capability may at least partially explain the differential effect of a low-fat diet on human breast cancer recurrence.", "title": "High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation." }, { "docid": "MED-2117", "text": "Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.", "title": "Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis." }, { "docid": "MED-4299", "text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.", "title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention." }, { "docid": "MED-3874", "text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.", "title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery" }, { "docid": "MED-4885", "text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.", "title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery" }, { "docid": "MED-1293", "text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.", "title": "Immunity: plants as effective mediators." }, { "docid": "MED-2808", "text": "Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.", "title": "Death by design: where curcumin sensitizes drug-resistant tumours." }, { "docid": "MED-3878", "text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.", "title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer" }, { "docid": "MED-1419", "text": "To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon adenocarcinoma cell line HT29 clone 19a as a target. The fluorescence and length of the tails of the comet images reflects the degree of DNA damage in single cells. The mean DNA damage, expressed as the ratio of tail intensity (fluorescence in the tail) to total intensity of the comet after incubation with faecal water from volunteers consuming diet 1 was about twice as high as for diet 2. The susceptibility of the cells incubated with faecal water to DNA damage caused by additional hydrogen peroxide treatment showed no significant differences between the two diets. Generation of oxidized pyrimidine and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer.", "title": "A diet high in fat and meat but low in dietary fibre increases the genotoxic potential of 'faecal water'." }, { "docid": "MED-1607", "text": "Background: As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC. Methods: The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55–69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses. Results: Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02). Conclusion: Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.", "title": "Long-term dietary sodium, potassium and fluid intake; exploring potential novel risk factors for renal cell cancer in the Netherlands Cohort Study on diet and cancer" }, { "docid": "MED-3106", "text": "PURPOSE OF REVIEW: The aryl hydrocarbon receptor (AhR), a transcription factor activated by a large number of environmental agents, modulates the activity of immune and nonimmune cells in the gut, and may represent an important link between the environment and the immune perturbations which underlie the pathogenesis of inflammatory bowel disease. This review will summarize the current knowledge of the role of AhR in regulation of intestinal immune homeostasis and inflammation. RECENT FINDINGS: Activation of AhR by dietary ligands is necessary for the maintenance or expansion of innate immune cells in the gut, such as intraepithelial lymphocytes (IELs) and interleukin (IL)-22-producing lymphoid cells (ILC22). AhR-deficient mice lack IELs, have reduced number of ILC22 cells, and are more susceptible to bacterial infections and experimental colitis. In animal models, AhR activators inhibit proinflammatory cytokine synthesis and attenuate colitis by a pathway that involves IL-22. Analysis of AhR in the human gut reveals that intestinal T cells and natural killer cells isolated from Crohn's disease patients express low levels of AhR and respond to AhR ligands by downregulating inflammatory cytokines and upregulating IL-22. SUMMARY: These novel findings may help explain how environmental factors may regulate mucosal immune responses.", "title": "The aryl hydrocarbon receptor in inflammatory bowel disease: linking the environment to disease pathogenesis." }, { "docid": "MED-5185", "text": "There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub-tropical community. Measurement-error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22-0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15-5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons. Copyright 2006 Wiley-Liss, Inc.", "title": "Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study." }, { "docid": "MED-5048", "text": "Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.", "title": "Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells." }, { "docid": "MED-984", "text": "We investigated total, free and protein-bound plasma homocysteine, cysteine and cysteinylglycine in 13 subjects aged 24-29 y after a breakfast at 0900 h containing 15-18 g of protein and a dinner at 1500 h containing approximately 50 g of protein. Twelve subjects had normal fasting homocysteine (mean +/- SD, 7.6 +/- 1.1 mumol/L) and methionine concentrations (22.7 +/- 3.5 mumol/L) and were included in the statistical analyses. Breakfast caused a small but significant increase in plasma methionine (22.2 +/- 20.6%) and a brief, nonsignificant increase followed by a significant decline in free homocysteine. However, changes in total and bound homocysteine were small. After dinner, there was a marked increase in plasma methionine by 16.7 +/- 8.9 mumol/L (87.9 +/- 49%), which was associated with a rapid and marked increase in free homocysteine (33.7 +/- 19.6%, 4 h after dinner) and a moderate and slow increase in total (13.5 +/- 7.5%, 8 h) and protein-bound (12.6 +/- 9.4%, 8 h) homocysteine. After both meals, cysteine and cysteinylglycine concentrations seemed related to changes in homocysteine, because there were parallel fluctuations in the free:bound ratios of all three thiols. Dietary changes in plasma homocysteine will probably not affect the evaluation of vitamin deficiency states associated with moderate to severe hyperhomocysteinemia but may be of concern in the risk assessment of cardiovascular disease in patients with mild hyperhomocysteinemia. Synchronous fluctuations in the free:bound ratio of the plasma aminothiol compounds indicate that biological effects of homocysteine may be difficult to separate from effects due to associated changes in other aminothiol compounds.", "title": "Plasma concentrations of homocysteine and other aminothiol compounds are related to food intake in healthy human subjects." }, { "docid": "MED-1618", "text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.", "title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..." }, { "docid": "MED-2250", "text": "Chronic low-level cadmium (Cd) exposure is linked to kidney and cardiovascular disease, fractures, and cancer. Diet and smoking are primary sources of exposure in the general population. We analyzed urinary Cd in NHANES 1999-2008 to determine whether levels declined significantly over the decade for U.S. children, teens, and adults (nonsmokers and smokers) and, if so, factors influencing the decline(s). For each subpopulation, we modeled log urinary Cd using variable-threshold censored multiple regression. Models included individual-level covariates (age, gender, BMI, income, race/ethnicity/country of origin, education, survey period), smoking, housing (home age, water source, filter use), and diet (supplement use; 24-h calorie, fat, protein, micronutrient, and Cd-containing food intakes), creatinine, and survey year variables. Geometric mean urinary Cd (ng/mL) declined 20-25% in these subpopulations, and the regressions showed statistically significant declines in later years for teens and adults. While certain covariates were significantly associated with Cd by subpopulation (creatinine; age; BMI; race/ethnicity/origin; education; smokers in the home; serum cotinine; 24-h fat, Mg, Fe intakes; use of dietary supplements), they did not help explain the declines. Instead, unidentified time-related factors appeared responsible. Despite the declines, millions of Americans remain potentially at risk of adverse outcomes associated with low-level Cd exposure.", "title": "Urinary cadmium in the 1999-2008 U.S. National Health and Nutrition Examination Survey (NHANES)." }, { "docid": "MED-2848", "text": "Type 1 diabetes is increasing rapidly in many parts of the Western world, most evidently in Scandinavia. A low concordance rate of insulin-dependent diabetes mellitus among monozygotic twins clearly indicates that genetic risk factors may be necessary, but are not sufficient for the disease to occur. The strongest genetic risk markers are located in the HLA region of chromosome 6, but these DNA specificities differ in different populations. Risk genes are indicated in other chromosomes of the human genome, suggesting a complex interaction between genes and environment as the cause of the disease. The pathogenesis of the disease is proposed to be autoimmune in nature and environmental risk factors may either initiate autoimmunity or accelerate an already ongoing beta-cell destruction. Risk factors disclosed by epidemiological studies that may accelerate the pathogenetic process are: a cold environment, a high growth rate, infections and stressful life events. Risk factors that may initiate the autoimmune process include early exposure to cow's milk proteins, nitrosamines or early foetal events such as blood group incompatibility or foetal viral infections. In conclusion, population-based epidemiological studies have helped to confirm proposed aetiological models that have arisen from experimental research. These epidemiological studies have also introduced important new findings that may reveal the complex aetiology of the disease and advance understanding closer to the ultimate goal of primary prevention.", "title": "The aetiology of type 1 diabetes: an epidemiological perspective." }, { "docid": "MED-2794", "text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.", "title": "Dietary turmeric potentially reduces the risk of cancer." }, { "docid": "MED-1714", "text": "BACKGROUND: Western diets, obesity, and sedentary lifestyles are associated with increased cancer risk. The mechanisms responsible for this increased risk, however, are not clear. OBJECTIVE: We hypothesized that long-term low protein, low calorie intake and endurance exercise are associated with low concentrations of plasma growth factors and hormones that are linked to an increased risk of cancer. DESIGN: Plasma growth factors and hormones were evaluated in 21 sedentary subjects, who had been eating a low-protein, low-calorie diet for 4.4 +/- 2.8 y (x +/- SD age: 53.0 +/- 11 y); 21 endurance runners matched by body mass index (BMI; in kg/m2); and 21 age- and sex-matched sedentary subjects eating Western diets. RESULTS: BMI was lower in the low-protein, low-calorie diet (21.3 +/- 3.1) and runner (21.6 +/- 1.6) groups than in the Western diet (26.5 +/- 2.7; P < 0.005) group. Plasma concentrations of insulin, free sex hormones, leptin, and C-reactive protein were lower and sex hormone-binding globulin was higher in the low-protein, low-calorie diet and runner groups than in the sedentary Western diet group (all P < 0.05). Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet group (139 +/- 37 ng/mL and 0.033 +/- 0.01, respectively) than in the runner (177 +/- 37 ng/mL and 0.044 +/- 0.01, respectively) and sedentary Western (201 +/- 42 ng/mL and 0.046 +/- 0.01, respectively) diet groups (P < 0.005). CONCLUSIONS: Exercise training, decreased adiposity, and long-term consumption of a low-protein, low-calorie diet are associated with low plasma growth factors and hormones that are linked to an increased risk of cancer. Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass.", "title": "Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk." }, { "docid": "MED-2194", "text": "Scope Anthocyanins, the natural pigments in plant foods, have been associated with cancer prevention. However, the content of anthocyanins in staple foods is typically low and the mechanisms by which they exert anti-cancer activity is not yet fully defined. Methods and results We selected an anthocyanin-enriched purple-fleshed sweet potato clone, P40, and investigated its potential anti-cancer effect in both in vitro cell culture and in vivo animal model. In addition to a high level of total phenolics and antioxidant capacity, P40 possesses a high content of anthocyanins at 7.5 mg/g dry matter. Treatment of human colonic SW480 cancer cells with P40 anthocyanin extracts at 0–40 μM of peonidin-3-glucoside equivalent resulted in a dose-dependent decrease in cell number due to cytostatic arrest of cell cycle at G1 phase but not cytotoxicity. Furthermore, dietary P40 at 10–30% significantly suppressed azoxymethane-induced formation of aberrant crypt foci in the colons of CF-1 mice in conjunction with, at least in part, a lesser proliferative PCNA and a greater apoptotic caspase-3 expression in the colon mucosal epithelial cells. Conclusion These observations, coupled with both in vitro and in vivo studies reported here, suggest anthocyanin-enriched sweet potato P40 may protect against colorectal cancer by inducing cell cycle arrest, anti-proliferative and apoptotic mechanisms.", "title": "Role of Anthocyanin-enriched Purple-fleshed Sweet Potato P40 in Colorectal Cancer Prevention" }, { "docid": "MED-4457", "text": "Sulforaphane (SFR), an isothiocyanate from cruciferous vegetables, possesses growth-inhibiting and apoptosis-inducing activities in cancer cell lines. Recently, SFR has been shown to promote the mitochondrial formation of reactive oxygen species (ROS) in human cancer cell lines. The present study was undertaken to see whether SFR-derived ROS might cause DNA damage in cultured human cells, namely T limphoblastoid Jurkat and human umbilical vein endothelial cells (HUVEC). 1-3 h treatments with 10-30 microM SFR elicited intracellular ROS formation (as assayed with dihydrorhodamine, DHR, oxidation) as well as DNA breakage (as assessed with fast halo assay, FHA). These effects lacked cell-type specificity, since could be observed in both Jurkat and HUVEC. Differential-pH FHA analysis of damaged DNA showed that SFR causes frank DNA single strand breaks (SSBs); no DNA double strand breaks (DSBs) were found within the considered treatment times (up to 3 h). SFR-derived ROS were formed at the mitochondrial respiratory chain (MRC) level: indeed rotenone or myxothiazol (MRC Complex I and III inhibitors, respectively) abrogated ROS formation. Furthermore ROS were not formed in Jurkat cells pharmacologically depleted of respiring mitochondria (MRC-/Jurkat). Formation of ROS was causally linked to the induction of SSBs: indeed all the experimental conditions capable of preventing ROS formation also prevented the damage of nuclear DNA from SFR-intoxicated cells. As to the toxicological relevance of SSBs, we found that their prevention slightly but significantly attenuated SFR cytotoxicity, suggesting that high-dose SFR toxicity is the result of a complex series of events among which GSH depletion seems to play a pivotal role. In conclusion, the present study identifies a novel mechanism contributing to SFR toxicity which - since DNA damage is a prominent mechanism underlying the cytotoxic activity of established antineoplastic agents - might help to exploit the therapeutic value of SFR in anticancer drug protocols. Copyright 2010 Elsevier B.V. All rights reserved.", "title": "Sulforaphane induces DNA single strand breaks in cultured human cells." }, { "docid": "MED-4696", "text": "Several epidemiologic studies have shown that chronic inflammation predisposes individuals to various types of cancer. Many cancers arise from sites of infection, chronic irritation, and inflammation. Conversely, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumors. Natural bioactive compounds in dietary plant products including fruits, vegetables, grains, legumes, tea, and wine are claimed to help prevent cancer, degenerative diseases, and chronic and acute inflammation. Modern methods in cell and molecular biology allow us to understand the interactions of different natural bioactive compounds with basic mechanisms of inflammatory response. The molecular pathways of this cancer-related inflammation are now unraveled. Natural bioactive compounds exert anti-inflammatory activity by modulating pro-inflammatory gene expressions have shown promising chemopreventive activity. This review summarizes current knowledge on natural bioactive compounds that act through the signaling pathways and modulate inflammatory gene expressions, thus providing evidence for these substances in cancer chemopreventive action.", "title": "Modulation of inflammatory genes by natural dietary bioactive compounds." }, { "docid": "MED-1712", "text": "Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.", "title": "Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici..." }, { "docid": "MED-5203", "text": "Fiber is not digested by endogenous enzymes but is fermented by microbes principally in the large intestine. With fermentable energy available, microbes synthesize protein by using ammonia released by their enzymes from urea and other nitrogenous substances in ingesta and intestinal secretions. Fibber fermentation also yields fatty acids that lower the concentration of free ammonia by lowering pH. Fiber increases bulk and water of intestinal contents, shortens transit time, and decreases the concentration of toxic substances in contact with the intestinal mucosa. These processes decrease duration and intensity of exposure of the intestinal mucosa to free ammonia, the form of nitrogen that is most toxic and most readily absorbed by cells. At concentrations found in the lower bowel on usual Western diets, ammonia destroys cells, alters nucleic acid synthesis, increases intestinal mucosal cell mass, increases virus infections, favors growth of cancerous cells over noncancerous cells in tissue culture, and increases virus infections. Ammonia in the bowel increases as protein intake increases. The attributes of ammonia and the epidemiological evidence comparing populations that maintain low intakes of unrefined carbohydrate with those that consume high intakes of protein, fat, and refined carbohydrates implicate ammonia in carcinogenesis and other disease processes.", "title": "Diet and cell growth modulation by ammonia." } ]
220	Ca2+ cycling controls whole-body energy homeostasis in beige fat.	[ { "docid": "19205437", "text": "Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca2+ cycling by activation of α1- and/or β3-adrenergic receptors or the SERCA2b-RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca2+ cycling.", "title": "UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis" } ]	[ { "docid": "14865329", "text": "Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.", "title": "Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders" }, { "docid": "25050364", "text": "OBJECTIVE The proinflammatory cytokine interleukin-18 (IL-18) putatively modulates food intake and energy metabolism, but the effects of IL-18 in high-fat diet fed animals are unknown. Whether IL-18 alters basal metabolic rate or metabolic processes of living is unknown. Here, we tested the hypothesis that IL-18 modulates weight gain, energy intake, whole-body energy expenditure, and utilization of lipid as a fuel substrate in high-fat diet fed mice. METHODS Food intake, whole-body metabolism, and motor activity of IL-18 knockout mice were compared to those of wildtype littermates; anorectic effects of intracerebroventricular IL-18 administration were compared between IL-18 receptor knockout, IL-18/IL-18R knockout and wildtype mice. RESULTS Chow-reared IL-18 knockout mice were overweight at 6 months of age and then gained excess weight on both low-fat and high-fat diets, ate more high-fat diet, and showed reduced whole-body energy expenditure and increased respiratory exchange ratios. Reductions in energy expenditure of IL-18 knockout mice were seen across fasting vs. feeding conditions, low- vs. high-fat diets, high vs. low levels of physical activity and times of day, suggesting actions on basal metabolic rate. The circadian amplitude of energy expenditure, but not respiratory exchange ratio, food intake, or motor activity, also was blunted in IL-18 knockout mice. Central IL-18 administration reduced high-fat diet intake in wildtype mice, but not in mice lacking the IL-18 receptor. CONCLUSION The loss-of-function results support the hypothesis that endogenous IL-18 suppresses appetite and promote energy expenditure and lipid fuel substrate utilization not only during sickness, but also in healthy adults consuming high-fat diets.", "title": "Interleukin-18 null mutation increases weight and food intake and reduces energy expenditure and lipid substrate utilization in high-fat diet fed mice" }, { "docid": "23369842", "text": "Twenty-four hour whole body indirect calorimetry has been used to study the effects of feeding, during a sedentary test day, isoenergetic diets which varied in fat (3 or 40 per cent of total energy) and carbohydrate (82 or 45 per cent) content. Three groups of women were studied: lean, obese and 'post-obese' after slimming. Energy expenditure was greater in absolute terms in the obese women. Twenty-four hour energy expenditure was lower by only 3-7 per cent when fasting compared to that when fed to achieve energy balance. There were no large differences in energy expenditure between the two diets or between the groups but the thermogenic effect of the high carbohydrate diet was significantly greater than that of the high fat diet (5.8 vs 3.5 per cent of energy expenditure: P less than 0.01). The post-obese tended to have lower energy expenditure per kg FFM than controls when fasting and when high-fat fed, but this pattern was not shown by the obese. Sleeping energy expenditure was particularly low in the post-obese group when high-fat fed. Dirunal variations in RQ appear to show more marked rise in morning RQ from the nocturnal minimum in the obese and post-obese, which might be evidence for an energy-saving mechanism through greater availability of stored dietary carbohydrate.", "title": "Metabolic effects of isoenergetic nutrient exchange over 24 hours in relation to obesity in women." }, { "docid": "15535511", "text": "Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.", "title": "Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis." }, { "docid": "17973161", "text": "Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is correlated with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human brite/beige adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform in response to adenylate cyclase activation from being UCP1 negative to being UCP1 positive, which is a defining feature of the beige/brite phenotype, while displaying uncoupled respiration. When implanted into normal chow-fed, or into high-fat diet (HFD)-fed, glucose-intolerant NOD-scid IL2rg(null) (NSG) mice, brite/beige adipocytes activated in vitro enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Pro-angiogenic conditions therefore drive the proliferation of human beige/brite adipocyte progenitors, and activated beige/brite adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.", "title": "Human ‘brite / beige’ adipocytes develop from capillary networks and their implantation improves metabolic homeostasis in mice" }, { "docid": "11742219", "text": "Galanin (GAL) is known to stimulate feeding behavior. This peptide has different properties and functions from other feeding stimulants, e.g., neuropeptide Y and agouti-related protein. Hypothalamic GAL is relatively unresponsive to food deprivation and to changes in corticosterone, glucose utilization, dietary carbohydrate and leptin. This indicates that this peptide is not essential under conditions when food is scarce or low-energy, high-carbohydrate diets are being consumed. In contrast, recent evidence suggests that GAL in the paraventricular nucleus (PVN) functions in close relation to dietary fat and alcohol. In particular, it mediates functions that allow animals to adapt to conditions of positive energy balance involving excess consumption of these nutrients. This peptide in the PVN is stimulated by a high-fat diet and also by alcohol. It is stimulated by an increase in circulating lipids caused by a fat-rich meal or alcohol consumption, and it rises during the middle of the active feeding cycle, when fat consumption and triglycerides naturally rise. When centrally injected, GAL in the PVN increases the consumption of food and alcohol. Moreover, it produces a significantly stronger feeding response in rats maintained on a fat-rich diet, which also promotes alcohol intake. This evidence supports the existence of non-homeostatic, positive feedback circuits between GAL and both dietary fat and alcohol. These circuits are believed to contribute to the large meal size, over-consumption of alcohol, and obesity which are generally associated with fat-rich foods.", "title": "Regulation and effects of hypothalamic galanin: relation to dietary fat, alcohol ingestion, circulating lipids and energy homeostasis." }, { "docid": "21547032", "text": "Objective:In mice and in humans, treatment with the second-generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high-fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ.Design and Measurement:C57BL/6J mice received either a normal diet or a HF diet, and were administered daily dosages of OLZ (3 mg kg−1 body weight), alone or with APAP (30 mg kg−1 body weight) or THII (4.5 mg kg−1 body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined. Results:OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. As increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O2 uptake and H2O2 production, which were further exacerbated by OLZ. APAP, THII and the NADPH oxidase inhibitor, diphenyleneiodonium chloride, each abolished oxidative stress in WAT.Conclusions:We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment.", "title": "Protection from olanzapine-induced metabolic toxicity in mice by acetaminophen and tetrahydroindenoindole" }, { "docid": "11201004", "text": "Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.", "title": "Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity." }, { "docid": "11428884", "text": "Adipose tissue is an important metabolic organ, the dysfunction of which is associated with the development of obesity, diabetes mellitus, and cardiovascular disease. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is considered the master regulator of adipocyte differentiation and function. Although its cell-autonomous role in adipogenesis has been clearly demonstrated in cell culture, previous fat-specific knockouts of the murine PPARγ gene did not demonstrate a dramatic phenotype in vivo. Here, using Adipoq-Cre mice to drive adipose-specific recombination, we report a unique fat-specific PPARγ knockout (PPARγ FKO) mouse model with almost no visible brown and white adipose tissue at age 3 mo. As a consequence, PPARγ FKO mice had hugely enlarged pancreatic islets, massive fatty livers, and dramatically elevated levels of blood glucose and serum insulin accompanied by extreme insulin resistance. PPARγ FKO mice also exhibited delayed hair coat formation associated with absence of dermal fat, disrupted mammary gland development with loss of mammary fat pads, and high bone mass with loss of bone marrow fat, indicating the critical roles of adipose PPARγ in these tissues. Together, our data reveal the necessity of fat PPARγ in adipose formation, whole-body metabolic homeostasis, and normal development of fat-containing tissues.", "title": "Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARγ." }, { "docid": "1590744", "text": "The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions.", "title": "AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System" }, { "docid": "11238784", "text": "Liver X receptors (LXRs) and farnesoid X receptor (FXR) are nuclear receptors that function as intracellular sensors for sterols and bile acids, respectively. In response to their ligands, these receptors induce transcriptional responses that maintain a balanced, finely tuned regulation of cholesterol and bile acid metabolism. LXRs also permit the efficient storage of carbohydrate- and fat-derived energy, whereas FXR activation results in an overall decrease in triglyceride levels and modulation of glucose metabolism. The elegant, dual interplay between these two receptor systems suggests that they coevolved to constitute a highly sensitive and efficient system for the maintenance of total body fat and cholesterol homeostasis. Emerging evidence suggests that the tissue-specific action of these receptors is also crucial for the proper function of the cardiovascular, immune, reproductive, endocrine pancreas, renal, and central nervous systems. Together, LXRs and FXR represent potential therapeutic targets for the treatment and prevention of numerous metabolic and lipid-related diseases.", "title": "LXRS and FXR: the yin and yang of cholesterol and fat metabolism." }, { "docid": "23017040", "text": "Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. These studies examine the relationship between insulin responsiveness and visceral fat in MR and test whether, despite lower food intake observed in MR animals, decreased visceral fat accretion and preservation of insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf) control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks exhibit insulin, glucose, and leptin levels similar to control-fed animals and comparable amounts of visceral fat. Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF. In a separate cohort, insulin responses of older MR animals as measured by oral glucose challenge are similar to young animals. Longitudinal assessments of MR and CF through 112 weeks of age reveal that MR prevents age-associated increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1 levels decline much later, beginning at 112 weeks. Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.", "title": "Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction." }, { "docid": "20363389", "text": "In order to elucidate energy balance in the skeletal muscle, we cloned cDNA of a homologue of uncoupling protein (UCP) from rat skeletal muscle. We also cloned rat UCP-2 cDNA from rat brown adipose tissue (BAT). The UCP cloned from rat skeletal muscle showed 57% and 72% identity with rat UCP-1 and UCP-2. The mRNA was expressed abundantly in the skeletal muscle, moderately in the BAT, and slightly in the white adipose tissue (WAT) with a major band at 2.5 kb and a minor band at 2.8 kb, while the UCP-2 gene expression was widely detected in the whole body with substantial levels in the WAT and with slight levels in the skeletal muscle and BAT. The rat UCP cloned in the present study showed 86% identity with the recently cloned human UCP-3, which was also expressed abundantly in the skeletal muscle with a signal of 2.4 kb. Therefore, the rat UCP was considered to be rat UCP-3. In rats fed high-fat diet the UCP-3 gene expression was augmented 2-fold in the skeletal muscle while UCP-2 mRNA levels were increased significantly (1.6-fold) in the epididymal WAT. Augmented expression of UCPs may provide defense against high-fat induced obesity and impairment of glucose metabolism.", "title": "Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs: their gene expression in rats fed high-fat diet." }, { "docid": "17231273", "text": "Energy deficiency and dysfunction of the Na+, K+-ATPase are common consequences of many pathological insults. The nature and mechanism of cell injury induced by impaired Na+, K+-ATPase, however, are not well defined. We used cultured cortical neurons to examine the hypothesis that blocking the Na+, K+-ATPase induces apoptosis by depleting cellular K+ and, concurrently, induces necrotic injury in the same cells by increasing intracellular Ca2+ and Na+. The Na+, K+-ATPase inhibitor ouabain induced concentration-dependent neuronal death. Ouabain triggered transient neuronal cell swelling followed by cell shrinkage, accompanied by intracellular Ca2+ and Na+ increase, K+ decrease, cytochrome c release, caspase-3 activation, and DNA laddering. Electron microscopy revealed the coexistence of ultrastructural features of both apoptosis and necrosis in individual cells. The caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD-FMK) blocked >50% of ouabain-induced neuronal death. Potassium channel blockers or high K+ medium, but not Ca2+ channel blockade, prevented cytochrome c release, caspase activation, and DNA damage. Blocking of K+, Ca2+, or Na+ channels or high K+ medium each attenuated the ouabain-induced cell death; combined inhibition of K+ channels and Ca2+ or Na+ channels resulted in additional protection. Moreover, coapplication of Z-VAD-FMK and nifedipine produced virtually complete neuroprotection. These results suggest that the neuronal death associated with Na+, K+-pump failure consists of concurrent apoptotic and necrotic components, mediated by intracellular depletion of K+ and accumulation of Ca2+ and Na+, respectively. The ouabain-induced hybrid death may represent a distinct form of cell death related to the brain injury of inadequate energy supply and disrupted ion homeostasis.", "title": "Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in individual cultured cortical neurons" }, { "docid": "36558211", "text": "OBJECTIVES To explore the different characteristics of high and low fat consumers, in particular their macronutrient intake and body mass index. DESIGN Reanalysis of data from the Dietary and Nutritional Survey of British Adults. Comparisons were made between groups defined as high and low fat consumers on the basis of 7-day weighed food records considered to be valid for energy intake. Individuals were classified in two ways according to the percentage energy from fat (FAT%) and the absolute amount of fat consumed (FATg). The criteria for classification of the high FAT% being > 45% (high fat) and < or = 35% (low fat). For the FATg group the threshold for the high fat group was > 138 g/day (men) and > 102 g/day (women), and for the low fat group < 85 g/day (men) and < 70 g/day (women). SETTING Dietary data was collected from private households in Great Britain between 1986 and 1987. SUBJECTS From the total population of 2197, individuals who were slimming, ill or had an EI: BMR of < 1.2 were excluded in order to use data which was most likely to represent habitual energy intakes. From the remaining 1240 subjects, 10.8% of this sample (6.1% of the total population) were classified as low fat consumers (76 men and 58 women) and 15.4% high fat (8.7% of the total population, 93 men and 98 women). MAIN OUTCOME MEASURES Macronutrient consumption and body mass index (BMI). RESULTS 30% of the subjects changed fat group classification when the criteria of defining high and low fat groups altered from FAT% to FATg. Nutrient intakes differed according to definition of the groups. The high fat FATg group ate significantly more of all nutrients than the low fat FATg group. However, this was not seen for the FAT% analysis, with the high fat group eating more fat and less carbohydrate. The average BMI tended to be higher in the high fat than the low fat groups, particularly in the FATg analysis. However, the high fat group contained a wide range of BMIs. Further exploration of BMI in the high fat groups, showed that age (an 11-year difference) was the only variable to distinguish individuals in the top and bottom quartiles of BMI. CONCLUSIONS High and low fat consumers differ according to a number of variables, and this is affected by how these groups are defined (FAT% or FATg). High fat consumers tend to have a higher BMI than low fat consumers, but not all high fat consumers are overweight or obese.", "title": "High and low fat consumers, their macronutrient intake and body mass index: further analysis of the National Diet and Nutrition Survey of British Adults." }, { "docid": "12994780", "text": "Rationale:Atypical antipsychotic drugs (AAD) induce significant weight gain in female C57BL/6J mice. The effect of dietary fat on weight gain and serum lipids in this model is unknown. Objectives: Test the hypothesis that the obesigenic effects of these drugs are greater in the presence of a high-fat diet. Methods:Female C57BL/6J mice were treated with atypical antipsychotics for 3 weeks and fed either a low-fat or high-fat diet (4.6 vs 15.6% fat by wt). Food intake (FI), body weight (BW), body composition, and serum lipids were measured during treatment with optimized doses of olanzapine, quetiapine, and risperidone. Energy intake (EI) and feed efficiency (FE) were calculated. Group differences in change were analyzed via repeated measures analysis of variance (ANOVA). Serum lipid concentrations, EI and FE were compared using two-way ANOVA.Results:AAD-treated mice gained significantly more weight than controls after 3 weeks (P<0.001). Treatment and diet had significant effects on FI and EI over time (P<0.001). AAD-treated mice had significantly higher FE than controls (P<0.05); however, there was no significant drug by diet interaction (P=0.65). Risperidone low-fat mice gained significantly more absolute fat mass than placebo low-fat mice (P<0.05). All treatment groups, except quetiapine low-fat and olanzapine high-fat, gained significantly more absolute lean mass than placebo controls (P<0.05). Cholesterol levels were significantly lower in quetiapine and risperidone than placebo (P<0.05). Risperidone low-fat mice had significantly higher triglyceride levels than placebo and risperidone high-fat mice (P<0.05).Conclusions:A high-fat diet does not increase AAD-induced BW gain in female mice during a 3-week treatment period.", "title": "No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs" }, { "docid": "17150648", "text": "Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity.", "title": "Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes." }, { "docid": "1365188", "text": "Several data suggest that fermentable dietary fiber could play a role in the control of obesity and associated metabolic disorders. The aim of this study was to investigate the putative role of short chain fructo-oligosaccharide (OFS) - a non-digestible oligosaccharide - in mice fed a standard diet and in mice fed two distinct high fat diets inducing metabolic disorders associated to obesity. We confirmed, in mice, several effects previously shown in rats fed a standard diet enriched with OFS, namely an increase in total and empty caecum weight, a significant decrease in epididymal fat mass, and an increase in colonic and portal plasma glucagon-like peptide-1 (GLP-1), a phenomenon positively correlated with a higher colonic proglucagon mRNA level. Curiously, 4-week treatment with OFS added at the same dose induced different effects when added in the two different high fat diets. OFS decreased energy intake, body weight gain, glycemia, and epididymal fat mass only when added together with the high fat-carbohydrate free diet, in which OFS promoted colonic proglucagon expression and insulin secretion. Our results support an association between the increase in proglucagon expression in the proximal colon and OFS effects on glycemia, fat mass development, and/or body weight gain. In conclusion, dietary oligosaccharides would constitute an interesting class of dietary fibers promoting, in certain conditions, endogenous GLP-1 production, with beneficial physiological consequences. This remains to be proven in human studies.", "title": "Relation between colonic proglucagon expression and metabolic response to oligofructose in high fat diet-fed mice." }, { "docid": "33918970", "text": "OBJECTIVE Oligofructose (OFS) is a prebiotic that reduces energy intake and fat mass via changes in gut satiety hormones and microbiota. The effects of OFS may vary depending on predisposition to obesity. The aim of this study was to examine the effect of OFS in diet-induced obese (DIO) and diet-resistant (DR) rats. METHODS Adult, male DIO, and DR rats were randomized to: high-fat/high-sucrose (HFS) diet or HFS diet + 10% OFS for 6 weeks. Body composition, food intake, gut microbiota, plasma gut hormones, and cannabinoid CB(1) receptor expression in the nodose ganglia were measured. RESULTS OFS reduced body weight, energy intake, and fat mass in both phenotypes (P < 0.05). Select gut microbiota differed in DIO versus DR rats (P < 0.05), the differences being eliminated by OFS. OFS did not modify plasma ghrelin or CB(1) expression in nodose ganglia, but plasma levels of GIP were reduced and PYY were elevated (P < 0.05) by OFS. CONCLUSIONS OFS was able to reduce body weight and adiposity in both prone and resistant obese phenotypes. OFS-induced changes in gut microbiota profiles in DIO and DR rats, along with changes in gut hormone levels, likely contribute to the sustained lower body weights.", "title": "Interactive effects of oligofructose and obesity predisposition on gut hormones and microbiota in diet-induced obese rats." }, { "docid": "18084826", "text": "Accurate measurement of fat mass has become increasingly important with the increasing incidence of obesity. We assessed fat and muscle mass of Koreans with the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). We studied 10,456 subjects (aged 20 to 85 yr; 4,476 men, 5,980 women). Fat and muscle mass were measured by dual-energy x-ray absorptiometry. Reference values of body compositions were obtained using the LMS method. The fat mass index (FMI, body fat mass/height(2); kg/m(2)) of Korean men did not correlate with age (P = 0.452), but those of Korean women (P < 0.001) did. The ratio of percentage of fat in the trunk and legs was positively related with age in both the genders. The appendicular lean mass/height(2) (kg/m(2)) of Korean men was negatively related to age (P < 0.001). In women, this ratio increased with age (P < 0.001). When we defined obesity according to the FMI classification, the rates of obesity were 6.1% (FMI > 9 kg/m(2)) in men and 2.7% (FMI > 13 kg/m(2)) in women. It is concluded that the muscle mass decreases and obesity increases with aging in Korean men, whereas both fat mass and obesity increase with aging in Korean women.", "title": "Characteristics of Body Fat, Body Fat Percentage and Other Body Composition for Koreans from KNHANES IV" }, { "docid": "29025270", "text": "We examined the contributions of genetic factors and the family environment to human fatness in a sample of 540 adult Danish adoptees who were selected from a population of 3580 and divided into four weight classes: thin, median weight, overweight, and obese. There was a strong relation between the weight class of the adoptees and the body-mass index of their biologic parents - for the mothers, P less than 0.0001; for the fathers, P less than 0.02. There was no relation between the weight class of the adoptees and the body-mass index of their adoptive parents. Cumulative distributions of the body-mass index of parents showed similar results; there was a strong relation between the body-mass index of biologic parents and adoptee weight class and no relation between the index of adoptive parents and adoptee weight class. Furthermore, the relation between biologic parents and adoptees was not confined to the obesity weight class, but was present across the whole range of body fatness - from very thin to very fat. We conclude that genetic influences have an important role in determining human fatness in adults, whereas the family environment alone has no apparent effect.", "title": "An adoption study of human obesity." }, { "docid": "28845338", "text": "One of the primary limitations of many psychiatric medications is weight gain, the mechanism of which remains to be fully elucidated. We conducted a 2-week double-blind placebo-controlled study on weight gain with olanzapine, which is frequently but unpredictably associated with this side effect, to address the possible mechanisms of weight gain independent of changes in the psychiatric condition for which it is prescribed. Healthy male volunteers were randomly assigned to olanzapine (5 mg/day for 7 days, then 10 mg/day for 7 days) or a matching placebo. Of the 24 participants, 19 completed the study (olanzapine, n=13; placebo, n=6). Body weight, glucose, triglyceride, total cholesterol, lipid, leptin, insulin, and aldosterone levels, resting metabolic rate, body composition, physical activity, and 24-h dietary intake were assessed. A significant increase in weight as well as triglyceride, insulin, and leptin levels were found in the olanzapine group as a whole. In participants receiving olanzapine who actually gained weight (n=8), lean but not fat mass increased, as did insulin, fasting glucose, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein levels, whereas aldosterone levels decreased. There were no significant metabolic or endocrine changes in participants receiving placebo or in those receiving olanzapine who did not gain weight. Early metabolic changes appear to be independent of accumulation of fat.", "title": "Increased lean body mass as an early indicator of olanzapine-induced weight gain in healthy men." }, { "docid": "2575938", "text": "The relationships between children's activity, aerobic fitness, and fatness are unclear. Indirect estimates of activity, e.g., heart rate (HR) and recall, may mask any associations. The purpose of this study was to assess these relationships by using the Tritrac-R3D, a pedometer, and heart rate. Thirty-four children, ages 8-10 yr, participated in the study. The Tritrac and pedometer were worn for up to 6 days. HR was measured for 1 day. Activity measured by Tritrac or pedometer correlated positively to fitness in the whole group (Tritrac, r = 0.66; pedometer, r = 0.59; P < 0.01) and in boys and girls separately (P < 0.05) and correlated negatively to fatness in the whole group (r = -0.42, P < 0.05). In contrast, HR did not correlate significantly to fitness, and HR of >139 beats/min correlated positively to fatness in girls (r = 0.64, P < 0.05). This suggests that HR is misleading as a measure of activity. This study supports a positive relationship between activity and fitness and suggests a negative relationship between fatness and activity.", "title": "Relationship between activity levels, aerobic fitness, and body fat in 8- to 10-yr-old children." }, { "docid": "32955023", "text": "The expansion of white adipose tissue (WAT) in obesity involves de novo differentiation of new adipocytes; however, the cellular origin of these cells remains unclear. Here, we utilize Zfp423(GFP) reporter mice to characterize adipose mural (Pdgfrβ(+)) cells with varying levels of the preadipocyte commitment factor Zfp423. We find that adipose tissue contains distinct mural populations, with levels of Zfp423 distinguishing adipogenic from inflammatory-like mural cells. Using our \"MuralChaser\" lineage tracking system, we uncover adipose perivascular cells as developmental precursors of adipocytes formed in obesity, with adipogenesis and precursor abundance regulated in a depot-dependent manner. Interestingly, Pdgfrβ(+) cells do not significantly contribute to the initial cold-induced recruitment of beige adipocytes in WAT; it is only after prolonged cold exposure that these cells differentiate into beige adipocytes. These results provide genetic evidence for a mural cell origin of white adipocytes in obesity and suggest that beige adipogenesis may originate from multiple sources.", "title": "Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice." }, { "docid": "29691654", "text": "Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity.", "title": "Uncoupling Mitochondrial Respiration for Diabesity." }, { "docid": "20532591", "text": "White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposure. During cold-induced 'browning' of subcutaneous fat, most 'beige' adipocytes stem from de novo–differentiated adipocytes. During HFD feeding, epididymal fat initiates adipogenesis after 4 weeks, whereas subcutaneous fat undergoes hypertrophy for a period of up to 12 weeks. Gonadal fat develops postnatally, whereas subcutaneous fat develops between embryonic days 14 and 18. Our results highlight the extensive differences in adipogenic potential in various fat depots.", "title": "Tracking adipogenesis during white adipose tissue development, expansion and regeneration" }, { "docid": "13944805", "text": "KEY POINTS Maternal obesity reduces adipogenic progenitor density in offspring adipose tissue. The ability of adipose tissue expansion in the offspring of obese mothers is limited and is associated with metabolic dysfunction of adipose tissue when challenged with a high-fat diet. Maternal obesity induces DNA demethylation in the promoter of zinc finger protein 423, which renders progenitor cells with a high adipogenic capacity. Maternal obesity demonstrates long-term effects on the adipogenic capacity of progenitor cells in offspring adipose tissue, demonstrating a developmental programming effect. ABSTRACT Maternal obesity (MO) programs offspring obesity and metabolic disorders, although the underlying mechanisms remain poorly defined. Progenitor cells are the source of new adipocytes. The present study aimed to test whether MO epigenetically predisposes adipocyte progenitors in the fat of offspring to adipogenic differentiation and subsequent depletion, which leads to a failure of adipose tissue plasticity under positive energy balance, contributing to adipose tissue metabolic dysfunction. C57BL/6 female mice were fed either a control diet (10% energy from fat) or a high-fat diet (45% energy from fat) for 8 weeks before mating. Male offspring of control (Con) and obese (OB) dams were weaned onto a regular (Reg) or obesogenic (Obe) diet until 3 months of age. At weaning, male OB offspring had a higher expression of Zinc finger protein 423 (zfp423), a key transcription factor in adipogenesis, as well as lower DNA methylation of its promoter in progenitors of epididymal fat compared to Con offspring, which was correlated with enhanced adipogenic differentiation. At 3 months of age, progenitor density was 30.9 ± 9.7% lower in OB/Obe compared to Con/Obe mice, accompanied by a limited expansion of the adipocyte number when challenged with a high-energy diet. This difference was associated with lower DNA methylation in the zfp423 promoter in the epididymal fat of OB/Obe offspring, which was correlated with greater macrophage chemotactic protein-1 and hypoxia-inducible factor 1α expression. In summary, MO epigenetically limits the expansion capacity of offspring adipose tissue, providing an explanation for the adipose metabolic dysfunction of male offspring in the setting of MO.", "title": "Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice." }, { "docid": "12805683", "text": "Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs), precisely control energy metabolism. Consequently, these receptors are important targets for the treatment of metabolic diseases, including diabetes and obesity. A thorough understanding of NHR fat regulatory networks has been limited, however, by a lack of genetically tractable experimental systems. Here we show that deletion of the Caenorhabditis elegans NHR gene nhr-49 yielded worms with elevated fat content and shortened life span. Employing a quantitative RT-PCR screen, we found that nhr-49 influenced the expression of 13 genes involved in energy metabolism. Indeed, nhr-49 served as a key regulator of fat usage, modulating pathways that control the consumption of fat and maintain a normal balance of fatty acid saturation. We found that the two phenotypes of the nhr-49 knockout were linked to distinct pathways and were separable: The high-fat phenotype was due to reduced expression of enzymes in fatty acid β-oxidation, and the shortened adult life span resulted from impaired expression of a stearoyl-CoA desaturase. Despite its sequence relationship with the mammalian hepatocyte nuclear factor 4 receptor, the biological activities of nhr-49 were most similar to those of the mammalian PPARs, implying an evolutionarily conserved role for NHRs in modulating fat consumption and composition. Our findings in C. elegans provide novel insights into how NHR regulatory networks are coordinated to govern fat metabolism.", "title": "Nuclear Hormone Receptor NHR-49 Controls Fat Consumption and Fatty Acid Composition in C. elegans" }, { "docid": "10883736", "text": "CONTEXT The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved. OBJECTIVE To determine if patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion. DESIGN Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998. SETTING University hospital. PATIENTS Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age- and sex-matched controls. MAIN OUTCOME MEASURE Level of ATP 1 hour after fructose infusion in patients vs controls. RESULTS In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (P<.02 vs minimum ATP) but patients did not. Hence, patients' hepatic ATP levels were lower than those of controls at the end of the study (P = .04). Body mass index (BMI) correlated inversely with ATP recovery, even in controls (R = -0.768; P = .07). Although BMI was greater in patients than controls (P = .02) and correlated strongly with fatty liver and serum aminotransferase elevations, neither of the latter 2 parameters nor the histologic severity of fibrosis strongly predicted hepatic ATP recovery. CONCLUSIONS These data suggest that recovery from hepatic ATP depletion becomes progressively less efficient as body mass increases in healthy controls and is severely impaired in patients with obesity-related nonalcoholic steatohepatitis.", "title": "Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study." }, { "docid": "26902591", "text": "Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or β-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.", "title": "A switch from white to brown fat increases energy expenditure in cancer-associated cachexia." } ]
7219	Can a retail trader do bid-ask spread scalping through algo-trading?	[ { "docid": "36723", "text": "\"In US public stock markets there is no difference between the actions individual retail traders are \"\"permitted\"\" to take and the actions institutional/corporate traders are \"\"permitted\"\" to take. The only difference is the cost of those actions. For example, if you become a Registered Market Maker on, say, the BATS stock exchange, you'll get some amazing rebates and reduced transaction prices; however, in order to qualify for Registered Market Maker status you have to maintain constant orders in the book for hundreds of equities at significant volumes. An individual retail trader is certainly permitted to do that, but it's probably too expensive. Algorithmic trading is not the same as automated trading (algorithmic trading can be non-automated, and automated trading can be non-algorithmic), and both can be anywhere from low- to high-frequency. A low-frequency automated strategy is essentially indistinguishable from a person clicking their mouse several times per day, so: no, from a legal or regulatory perspective there is no special procedure an individual retail trader has to follow before s/he can automate a trading strategy. (Your broker, on the other hand, may have all sorts of hoops for you to jump through in order to use their automation platform.) Last (but certainly not least) you will almost certainly lose money hand over fist attempting bid-ask scalping as an individual retail trader, whether your approach is algorithmic or not, automated or not. Why? Because the only way to succeed at bid-ask scalping is to (a) always be at/near the front of the queue when a price change occurs in your favor, and (b) always cancel your resting orders before they are executed when a price change occurs against you. Unless your algorithms are smarter than every other algorithm in the industry, an individual retail trader operating through a broker's trading platform cannot react quickly enough to succeed at either of those. You would have to eschew the broker and buy direct market access to even have a chance, and that's the point at which you're no longer a retail trader. Good luck!\"", "title": "" } ]	[ { "docid": "69197", "text": "Quote driven markets are the predecessors to the modern securities market. Before electronic trading and HFTs specifically, trading was thin and onerous. Today, the average investor can open up a web page, type in a security, and buy at the narrowest spread permitted by regulators with anyone else who wants to take the other side. Before the lines between market maker and speculator became blurred to indistinction, a market maker was one who was contractually obligated to an exchange to provide a bid and ask for a given security on said exchange even though at heart a market maker is still simply a trader despite the obligation. A market maker would simultaneously buy a large amount of securities privately and short the same amount to have no directional bias, exposure to the direction of the security, and commence to making the market. The market maker would estimate its cost basis for the security based upon those initial trades and provide a bid and ask appropriate for the given level of volume. If volumes were high, the spread would be low and vice versa. Market makers who survived crashes and spikes would forgo the potential profit in always providing a steady price and spread, ie increased volume otherwise known as revenue, to maintain no directional bias. In other words, if there were suddenly many buyers and no sellers, hitting the market maker's ask, the MM would raise the ask rapidly in proportion to the increased exposure while leaving the bid somewhere below the cost basis. Eventually, a seller would arise and hit the MM's bid, bringing the market maker's inventory back into balance, and narrowing the spread that particular MM could provide since a responsible MM's ask could rise very high very quickly if a lack of its volume relative to its inventory made inventory too costly. This was temporarily extremely costly to the trader if there were few market makers on the security the trader was trading or already exposed to. Market makers prefer to profit from the spread, bidding below some predetermined price, based upon the cost basis of the market maker's inventory, while asking above that same predetermined cost basis. Traders profit from taking exposure to a security's direction or lack thereof in the case of some options traders. Because of electronic trading, liquidity rebates offered by exchanges not only to contractually obligated official market makers but also to any trader who posts a limit order that another trader hits, and algorithms that become better by the day, market making HFTs have supplanted the traditional market maker, and there are many HFTs where there previously were few official market makers. This speed and diversification of risk across many many algorithmically market making HFTs have kept spreads to the minimum on large equities and have reduced the same for the smallest equities on major exchanges. Orders and quotes are essentially identical. Both are double sided auction markets with impermenant bids and asks. The difference lies in that non-market makers, specialists, etc. orders are not shown to the rest of the market, providing an informational advantage to MMs and an informational disadvantage to the trader. Before electronic trading, this construct was of no consequence since trader orders were infrequent. With the prevalence of HFTs, the informational disadvantage has become more costly, so order driven markets now prevail with much lower spreads and accelerated volumes even though market share for the major exchanges has dropped rapidly and hyperaccelerated number of trades even though the size of individual trades have fallen. The worst aspect of the quote driven market was that traders could not directly trade with each other, so all trades had to go between a market maker, specialist, etc. While this may seem to have increased cost to a trader who could only trade with another trader by being arbitraged by a MM et al, paying more than what another trader was willing to sell, these costs were dwarfed by the potential absence of those market makers. Without a bid or ask at any given time, there could be no trade, so the costs were momentarily infinite. In essence, a quote driven market protects market makers from the competition of traders. While necessary in the days where paper receipts were carted from brokerage to brokerage, and the trader did not dedicate itself to round the clock trading, it has no place in a computerized market. It is more costly to the trader to use such a market, explaining quote driven markets' rapid exit.", "title": "" }, { "docid": "464810", "text": "In general, liquidity is a good thing, because it means it is easy for you to buy or sell a stock. Since high liquidity stocks have a lot of trading, the bid-ask spreads tend to be pretty low. That means you can go into the market and trade easily and cheaply at just about any time. For low liquidity stocks, the bid-ask spreads can get pretty high, so it can make it hard or expensive to get into or out of your trades. On the flip side, everyone pays attention to high liquidity stocks, so it's harder to get an edge in your trading. For a company like Microsoft there are 30-50 full time analysts that cover them, thousands of professional traders and millions of investors in general all reading the same new articles and looking through the same financials as you. But in low liquidity stocks, there probably aren't any analysts, a few professional traders and maybe a few thousand total investors, so it can be easier to find a good buy (or sell). In general, high liquidity doesn't mean that everyone is selling or everyone is buy, it just means everyone is trading.", "title": "" }, { "docid": "53041", "text": "\"A \"\"market maker\"\" is someone that is contractually bound, by the exchange, to provide both bid and ask prices for a given volume (e.g. 5000 shares). A single market maker usually covers many stocks, and a single stock is usually covered by many market makers. The NYSE has \"\"specialists\"\" that are market makers that also performed a few other roles in the management of trading for a stock, and usually a single issue on the NYSE is covered by only one market maker. Market makers are often middlemen between brokers (ignoring stuff like dark pools, and the fact that brokers will often trade stocks internally among their own clients before going to the exchange). Historically, the market makers gave up buy/sell discretion in exchange for being the \"\"go-to guys\"\" for anyone wanting to trade in that stock. When you told your broker to buy a stock for you, he didn't hook you up with another retail investor; he went to the market maker. Market makers would also sometimes find investors willing to step in when more liquidity was needed for a security. They were like other floor traders; they hung out on the exchange floors and interacted with traders to buy and sell stocks. Traders came to them when they wanted to buy one of the specialist's issues. There was no public order book; just ticker tape and a quote. It was up to the market maker to maintain that order book. Since they are effectively forbidden from being one-sided traders in a security, their profit comes from the bid-ask spread. Being the counter-party to almost every trade, they'd make profit from always selling above where they were buying. (Except when the price moved quickly -- the downside to this arrangement.) \"\"The spread goes to the market maker\"\" is just stating that the profit implicit in the spread gets consumed by the market maker. With the switch to ECNs, the role of the market maker has changed. For example, ForEx trading firms tend to act as market makers to their customers. On ECNs, the invisible, anonymous guy at the other end of most trades is often a market maker, still performing his traditional role. Yet brokers can interact directly with each other now, rather than relying on the market maker's book. With modern online investing and public order books, retail investors might even be trading directly with each other. Market makers are still out there; in part, they perform a service sold by an Exchange to the companies that choose to be listed on that exchange. That service has changed to helping tamp volatility during normal high-volatility periods (such as at open and close).\"", "title": "" }, { "docid": "233635", "text": "\"As proposed: Buy 100 oz of gold at $1240 spot = -$124,000 Sell 1 Aug 2014 Future for $1256 = $125,600 Profit $1,600 Alternative Risk-Free Investment: 1 year CD @ 1% would earn $1240 on $124,000 investment. Rate from ads on www.bankrate.com \"\"Real\"\" Profit All you are really being paid for this trade is the difference between the profit $1,600 and the opportunity for $1240 in risk free earnings. That's only $360 or around 0.3%/year. Pitfalls of trying to do this: Many retail futures brokers are set up for speculative traders and do not want to deal with customers selling contracts against delivery, or buying for delivery. If you are a trader you have to keep margin money on deposit. This can be a T-note at some brokerages, but currently T-notes pay almost 0%. If the price of gold rises and you are short a future in gold, then you need to deposit more margin money. If gold went back up to $1500/oz, that could be $24,400. If you need to borrow this money, the interest will eat into a very slim profit margin over the risk free rate. Since you can't deliver, the trades have to be reversed. Although futures trades have cheap commissions ~$5/trade, the bid/ask spread, even at 1 grid, is not so minimal. Also there is often noisy jitter in the price. The spot market in physical gold may have a higher bid/ask spread. You might be able to eliminate some of these issues by trading as a hedger or for delivery. Good luck finding a broker to let you do this... but the issue here for gold is that you'd need to trade in depository receipts for gold that is acceptable for delivery, instead of trading physical gold. To deliver physical gold it would likely have to be tested and certified, which costs money. By the time you've researched this, you'll either discover some more costs associated with it or could have spent your time making more money elsewhere.\"", "title": "" }, { "docid": "148141", "text": "\"In essence the problem that the OP identified is not that the FX market itself has poor liquidity but that retail FX brokerage sometimes have poor counterparty risk management. The problem is the actual business model that many FX brokerages have. Most FX brokerages are themselves customers of much larger money center banks that are very well capitalized and provide ample liquidity. By liquidity I mean the ability to put on a position of relatively decent size (long EURUSD say) at any particular time with a small price impact relative to where it is trading. For spot FX, intraday bid/ask spreads are extremely small, on the order of fractions of pips for majors (EUR/USD/GBP/JPY/CHF). Even in extremely volatile situations it rarely becomes much larger than a few pips for positions of 1 to 10 Million USD equivalent notional value in the institutional market. Given that retail traders rarely trade that large a position, the FX spot market is essentially very liquid in that respect. The problem is that there are retail brokerages whose business model is to encourage excessive trading in the hopes of capturing that spread, but not guaranteeing that it has enough capital to always meet all client obligations. What does get retail traders in trouble is that most are unaware that they are not actually trading on an exchange like with stocks. Every bid and ask they see on the screen the moment they execute a trade is done against that FX brokerage, and not some other trader in a transparent central limit order book. This has some deep implications. One is the nifty attribute that you rarely pay \"\"commission\"\" to do FX trades unlike in stock trading. Why? Because they build that cost into the quotes they give you. In sleepy markets, buyers and sellers cancel out, they just \"\"capture\"\" that spread which is the desired outcome when that business model functions well. There are two situations where the brokerage's might lose money and capital becomes very important. In extremely volatile markets, every one of their clients may want to sell for some reason, this forces the FX brokers to accumulate a large position in the opposite side that they have to offload. They will trade in the institutional market with other brokerages to net out their positions so that they are as close to flat as possible. In the process, since bid/ask spreads in the institutional market is tighter than within their own brokerage by design, they should still make money while not taking much risk. However, if they are not fast enough, or if they do not have enough capital, the brokerage's position might move against them too quickly which may cause them lose all their capital and go belly up. The brokerage is net flat, but there are huge offsetting positions amongst its clients. In the example of the Swiss Franc revaluation in early 2015, a sudden pop of 10-20% would have effectively meant that money in client accounts that were on the wrong side of the trade could not cover those on the other side. When this happens, it is theoretically the brokerage's job to close out these positions before it wipes out the value of the client accounts, however it would have been impossible to do so since there were no prices in between the instantaneous pop in which the brokerage could have terminated their client's losing positions, and offload the risk in the institutional market. Since it's extremely hard to ask for more money than exist in the client accounts, those with strong capital positions simply ate the loss (such as Oanda), those that fared worse went belly up. The irony here is that the more leverage the brokerage gave to their clients, the less money would have been available to cover losses in such an event. Using an example to illustrate: say client A is long 1 contract at $100 and client B is short 1 contract at $100. The brokerage is thus net flat. If the brokerage had given 10:1 leverage, then there would be $10 in each client's account. Now instantaneously market moves down $10. Client A loses $10 and client B is up $10. Brokerage simply closes client A's position, gives $10 to client B. The brokerage is still long against client B however, so now it has to go into the institutional market to be short 1 contract at $90. The brokerage again is net flat, and no money actually goes in or out of the firm. Had the brokerage given 50:1 leverage however, client A only has $2 in the account. This would cause the brokerage close client A's position. The brokerage is still long against client B, but has only $2 and would have to \"\"eat the loss\"\" for $8 to honor client B's position, and if it could not do that, then it technically became insolvent since it owes more money to its clients than it has in assets. This is exactly the reason there have been regulations in the US to limit the amount of leverage FX brokerages are allowed to offer to clients, to assure the brokerage has enough capital to pay what is owed to clients.\"", "title": "" }, { "docid": "417365", "text": "\"First, as @littleadv mentions, and as I've pointed out before, anyone who participates in a market using limit orders (which, by the way, should be every non-professional investor) is by definition a market maker. So, I will assume that your question pertains both to official market makers and to \"\"retail investors\"\" using limit orders. When you remark that there are such \"\"tight spreads\"\" in \"\"liquid assets\"\", what you are really saying is \"\"wow, look at all the market makers in these products!\"\" That's the benefit of electronic trading and algorithmic traders -- millions of participants each with their own opinion of the value of a financial instrument, trying to find people who have very specifically opposing opinions of the value of that same instrument. This is called price discovery, and is the entire point of financial markets. So, you ask why are there all these market makers present to create such tight spreads in assets like SPY? Answer: Because they can make money in these markets: Imagine (towards a contradiction) that market makers thought they couldn't make money by offering tight spreads in SPY, and so SPY had a wider spread than it actually does. For example, say the highest bid for SPY was $99.98 and the lowest ask was $100.01. Now imagine that a market maker with perfect knowledge of the future came along knowing that he would be able to sell SPY for $100.01 in 5 minutes. Then he would load up as many buy orders as he could for $100.00 or lower. (He wouldn't bid $100.01 or higher because those trades would not be profitable according to his information -- at least not 5 minutes from now.) So the spread had previously been $0.03 and then suddenly it was $0.01, all because a market maker with better information came along and realized he could make money by creating a tighter market! Now, nobody has perfect knowledge of the future, which is why markets are never infinitely tight or infinitely liquid. Each market maker has to weigh possible profits against the probability that those profits will actually turn into losses. But if one market maker decides not to participate in a particular instrument, there's bound to be another market maker who will happily take his place. So the very fact that there are so many market participants with resting buy/sell orders for SPY right now is proof that there are market makers able to make money doing so. If they could not make money, they wouldn't be there, and the spread would be wider. 10-15 years ago, before electronic trading and algorithmic trading, the number of market participants was far lower, and the spreads were far wider, meaning retail investors like you and me had a much harder time making money. The only people making money were the institutional investors, the brokers, and the exchanges. Now that all these new millions of players are present in the market, retail investors like you and me get to participate and make money too.\"", "title": "" }, { "docid": "159822", "text": "\"ETFs are well suited to day trading, but you should be mindful of the bid-ask spread. See article: Commission-free ETFs are a great way to save money, but watch the bid-ask spread too. Bid-ask spread is largely a function of liquidity, or the volume of buyers and sellers for an asset during a particular moment in time. ... It may be more difficult to trade certain assets that are less liquid, where bid-ask spreads can be higher. Think some penny stocks. If you have the choice, compare the spreads of the ETF and the target stock. Longer-term \"\"keep & hold\"\" trading on ETFs tracking futures can be somewhat disadvantageous. Futures contracts roll-over every month. Exchange traders have to sell and buy in on the next contract. ETFs don't reflect the price differential between the futures contract. See here for more detail on that: Positioning For An Oil ETF Rebound? Watch For Contango Contango occurs when the price on a futures contract is higher than the expected future spot price, which creates the upward sloping curve on future commodity prices over time. Essentially, the phenomenon reflects a current spot price that is lower than the futures price. ... While this phenomena is a normal occurrence in the futures market, contango can have a negative effect on ETFs.\"", "title": "" }, { "docid": "189858", "text": "While open interest usually correlates to volume, the mark of liquidity is the bid ask spread. Even when trading options with spreads as large as an ask 2x the bid, a more realistic price that traders are willing to accept lies somewhere in the middle. Any option can easily be exited at intrinsic value: underlying price - exercise price for calls, exercise price - underlying price for puts. For illiquid options, this will be the best price obtained. For longer term options, something closer to the theoretical price is still possible. If an underlying is extremely liquid, yet the options aren't quite then options traders will be much more ready to trade at the theoretical price. For exiting illiquid options, small, < 4 contracts, and infrequent, > 30 minute intervals, orders are more likely to be filled closer to the theoretical price; however, if one's sells are the only trades, traders on the other side will take note and accept ever lowering implied volatilities. With knowledge of what traders will accept, it is always more optimal to trade out of options rather than exercise because of the added costs and uncertainty involved with exercising and liquidating.", "title": "" }, { "docid": "353396", "text": "\"Say we have stock XYZ that costs $50 this second. It doesn't cost XYZ this second. The market price only reflects the last price at which the security traded. It doesn't mean that if you'll get that price when you place an order. The price you get if/when your order is filled is determined by the bid/ask spreads. Why would people sell below the current price, and not within the range of the bid/ask? Someone may be willing to sell at an ask price of $47 simply because that's the best price they think they can sell the security for. Keep in mind that the \"\"someone\"\" may be a computer that determined that $47 is a reasonable ask price. Remember that bid/ask spreads aren't fixed, and there can be multiple bid/ask prices in a market at any given time. Your buy order was filled because at the time, someone else in the market was willing to sell you the security for the same price as your bid price. Your respective buy/sell orders were matched based on their price (and volume, conditional orders, etc). These questions may be helpful to you as well: Can someone explain a stock's \"\"bid\"\" vs. \"\"ask\"\" price relative to \"\"current\"\" price? Bids and asks in case of market order Can a trade happen \"\"in between\"\" the bid and ask price? Also, you say you're a day trader. If that's so, I strongly recommend getting a better grasp on the basics of market mechanics before committing any more capital. Trading without understanding how markets work at the most fundamental levels is a recipe for disaster.\"", "title": "" }, { "docid": "272929", "text": "I don't know why a financial investor or a retail trader would do this. But I can guess why a market maker in options would do this. Let us say you buy an option from an option market maker and the market maker sold the option to you. He made a small profit in the bid-ask spread but now he is holding a short position in the option with unlimited risk exposure. So to protect himself, he will take an offsetting position in the underlying and become delta neutral, so that his position is not affected by the moves in the underlying. In the end, he can do this because he is not in the market to make money by betting on direction, unlike the rest of us poor mortals. He is making money from the bid-ask spread. So to ensure that his profits are not eroded by an adverse move in the underlying, he will continuously seek to be delta neutral. But once again, this is for a market maker. For market takers like us, I still don't understand why we would need to delta hedge.", "title": "" }, { "docid": "513055", "text": "Most of the Indian Brokers started offering API's to retail client these days. And NSE Exchange also supports algo trading at retail level. Currently two levels of API are offered. 1)Semi-automatic or one touch trading (Retail Traders) 2)Fully Automatic ( Dealers) I had tested the API with a discount broker www.tradejini.com and it is good at retail level. But to make your trading systems fully automatic you need to pass NISM Series VIII certification (Dealer Certification) and have to take dealer terminals from the broker. You also have to register as a dealer and have to take permission from exchange to run your algos fully automated. Without Exchange permission it is illegal to involve in algo trading.", "title": "" }, { "docid": "124038", "text": "Some liquidity Since you're using IB, and you seem to be an investor not a trader, so you won't notice especially if you walk your orders, but you will suffer the bid/ask spread as everyone else albeit wider. If buying, the best strategy unless if one is time constrained is to walk the entire bid from the best bid to the best ask. It is highly likely that someone will hit your order before you hit the best ask. If they don't, as a long term investor, the few pennies won't make or break you, especially if the price per share is 100 USD equivalent, but it is an excellent habit to form and fun. Since you're buying ETFs, even though your orders are small, you would be adding liquidity to your market, helping it become more efficient because your orders could be used to arbitrage against all of the ETF's holdings, in turn providing liquidity for those holdings. No liquidity This could only be done with an extremely low cost broker like IB because the trading commissions would make it prohibitively expensive. There are huge risks when trading an illiquid security such as VEUR. EWL would be much less risky thus less expensive. Securities with no liquidity can be traded, but they must be traded very carefully. In the case of a security that can only attract about 20 shares per day in volume, only single shares should be bid. The market makers, suffering from a dearth in volume may not even be willing to haggle; therefore, the only recourse is a statistical arbitrageur, who will attempt to profit from the spread between other more liquid versions of the security. Considering the available alternative, VEUR is not recommended to trade.", "title": "" }, { "docid": "164008", "text": "The everyday investor buys at the ask and sells at the bid but the market maker does the opposite This is misleading; it has nothing to do with being either an investor or a market maker. It is dependent on the type of order that is submitted. When a market trades at the ask, this means that a buy market order has interacted with a sell limit order at the limit price. When a market trades at the bid, this means that a sell market order has interacted with a buy limit order at the limit price. An ordinary investor can do exactly the same as a market maker and submit limit orders. Furthermore, they can sit on both sides of the bid and ask exactly as a market maker does. In the days before high frequency trading this was quite common (an example being Daytek, whose traders were notorious for stepping in front of the designated market maker's bid/ask on the Island ECN). An order executes ONLY when both bid and ask meet. (bid = ask) This is completely incorrect. A transaction occurs when an active (marketable) order is matched with a passive (limit book) order. If the passive order is a sell limit then the trade has occurred at the ask, and if it is a buy limit the trade has occurred at the bid. The active orders are not bids and asks. The only exception to this would be if the bid and ask have become crossed. When a seller steps in, he does so with an ask that's lower than the stock's current ask Almost correct; he does so with an order that's lower than the stock's current ask. If it's a marketable order it will fill the front queued best bid, and if it's a limit order his becomes the new ask price. A trade does not need to occur at this price for it to become the ask. This is wrong, market makers are the opposite party to you so the prices are the other way around for them. This is wrong. There is no distinction between the market maker and yourself or any other member of the public (beside the fact that designated market makers on some exchanges are obliged to post both a bid and ask at all times). You can open an account with any broker and do exactly the same as a market maker does (although with nothing like the speed that a high frequency market-making firm can, hence likely making you uncompetitive in this arena). The prices a market maker sees and the types of orders that they are able to use to realize them are exactly the same as for any other trader.", "title": "" }, { "docid": "35340", "text": "Investopedia has a section in their article about currency trading that states: The FX market does not have commissions. Unlike exchange-based markets, FX is a principals-only market. FX firms are dealers, not brokers. This is a critical distinction that all investors must understand. Unlike brokers, dealers assume market risk by serving as a counterparty to the investor's trade. They do not charge commission; instead, they make their money through the bid-ask spread. Principals-only means that the only parties to a transaction are agents who actively bear risk by taking one side of the transaction. There are forex brokers who charge what's called a commission, based on the spread. Investopedia has another article about the commission structure in the forex market that states: There are three forms of commission used by brokers in forex. Some firms offer a fixed spread, others offer a variable spread and still others charge a commission based on a percentage of the spread. So yes, there are forex brokers who charge a commission, but this paragraph is saying mostly the same thing as the first paragraph. The brokers make their money through the bid-ask spread; how they do so varies, and sometimes they call this charge a commission, sometimes they don't. All of the information above differs from the stock markets, however, in which The broker takes the order to an exchange and attempts to execute it as per the customer's instructions. For providing this service, the broker is paid a commission when the customer buys and sells the tradable instrument. The broker isn't taking a side in the trade, so he's not making money on the spread. He's performing the service of taking the order to an exchange an attempting to execute it, and for that, he charges a commission.", "title": "" }, { "docid": "414036", "text": "\"During market hours, there are a lot of dealers offering to buy and sell all exchange traded stocks. Dealers don't actually care about the company's fundamentals and they set their prices purely based on order flow. If more people start to buy than sell, the dealer notices his inventory going down and starts upping the price (both his bid and ask). There are also traders who may not be \"\"dealers\"\", but are willing to sell if the price goes high enough or buy if the price goes low enough. This keeps the prices humming along smoothly. During normal trading hours, if you buy something and turn around and sell it two minutes later, you'll probably be losing a couple cents per share. Outside normal market hours, the dealers who continue to have a bid and ask listed know that they don't have access to good price information -- there isn't a liquid market of continuous buying and selling for the dealer to set prices he considers safe. So what does he do? He widens the spread. He doesn't know what the market will open tomorrow at and doesn't know if he'll be able to react quickly to news. So instead of bidding $34.48 and offering at $34.52, he'll move that out to $33 and $36. The dealer still makes money sometimes off this because maybe some trader realized that he has options expiring tomorrow, or a short position that he's going to get a margin call on, or some kind of event that pretty much forces him to trade. Or maybe he's just panicking and overreacting to some news. So why not trade after hours? Because there's no liquidity, and trading when there's no liquidity costs you a lot.\"", "title": "" }, { "docid": "533717", "text": "\">The success rate is terrible. This may be quite true, but how many \"\"careers\"\" exist that all you need is $500 and a bank account? One can call their self a trader in less than a week; apply for online broker, transfer funds: you are now a trader. >I also wanted to see if it is still feasible with all of the algo trading and stuff that has been dominating the market versus an individual trader. Either I'm not drinking the Kool-Aid or I'm just completely missing something here, but I don't care about algo trading. One can go on about algos, HFT, and traders at big banks and insiders, but what does this have to do with me? People invest/trade different ways and none of the aforementioned methods create a market that doesn't allow small, amateur traders to make money. The market isn't on or off, it's moves in fluid motions; sometimes smooth, sometimes erratic. When people bring up big banks or algos, I feel as if they think the market acts like a [square wave](http://www.thedawstudio.com/wp-admin/Images/Sound_Waves/Square_Wave.jpg) and once the info is out it's too late. But markets take time to make movements. Just don't be left holding the bag.\"", "title": "" }, { "docid": "98638", "text": "No. You're lucky, maybe, but not really a successful investor. Warren Buffet is, you're not him. Sometimes it is easier to pick stocks to bid on, sometimes its harder. I got my successes too. It is easier on a raising market, especially when it is recovering after a deep fall, like now. But generally it is very hard to beat the market. You need to remember that an individual investor, not backed by deep pockets, algo-trading and an army of analysts, is in a disadvantage on the market by definition. So what can you do? Get the deep pockets, algo-trading and an army of analysts. How? By pooling with others - investing through funds.", "title": "" }, { "docid": "599523", "text": "\"I'm not sure the term actually has a clear meaning. We can think of \"\"what does this mean\"\" in two ways: its broad semantic/metaphorical meaning, and its mechanical \"\"what actual variables in the market represent this quantity\"\". Net buying/selling have a clear meaning in the former sense by analogy to the basic concept of supply and demand in equilibrium markets. It's not as clear what their meaning should be in the latter sense. Roughly, as the top comment notes, you could say that a price decrease is because of net selling at the previous price level, while a price rise is driven by net buying at the previous price level. But in terms of actual market mechanics, the only way prices move is by matching of a buyer and a seller, so every market transaction inherently represents an instantaneous balance across the bid/ask spread. So then we could think about the notion of orders. Actual transactions only occur in balance, but there is a whole book of standing orders at various prices. So maybe we could use some measure of the volume at various price levels in each of the bid/ask books to decide some notion of net buying/selling. But again, actual transactions occur only when matched across the spread. If a significant order volume is added on one side or the other, but at a price far away from the bid/offer - far enough that an actual trade at that price is unlikely to occur - should that be included in the notion of net buying/selling? Presumably there is some price distance from the bid/offer where the orders don't matter for net buying/selling. I'm sure you'd find a lot of buyers for BRK.A at $1, but that's completely irrelevant to the notion of net buying/selling in BRK.A. Maybe the closest thing I can think of in terms of actual market mechanics is the comparative total volumes during the period that would still have been executed if forced to execute at the end of period price. Assuming that traders' valuations are fixed through the period in question, and trading occurs on the basis of fundamentals (which I know isn't a good assumption in practice, but the impact of price history upon future price is too complex for this analysis), we have two cases. If price falls, we can assume all buyers who executed above the last price in the period would have happily bought at the last price (saving money), while all sellers who executed below the last price in the period would also be happy to sell for more. The former will be larger than the latter. If the price rises, the reverse is true.\"", "title": "" }, { "docid": "402482", "text": "You can always trade at bid or ask price (depending if you are selling or buying). Market price is the price the last transaction was executed at so you may not be able to get that. If your order is large then you may not even be able to get bid/ask but should look at the depth of the order book (ie what prices are other market participants asking for and what is the size of their order). Usually only fast traders will trade at bid/ask, those who believe the price move is imminent. If you are a long term trader you can often get better than bid or ask by placing a limit order and waiting until a market participant takes your offer.", "title": "" }, { "docid": "322798", "text": "\"I think for this a picture is worth a thousand words. This is a \"\"depth chart\"\" that I pulled from google images, specifically because it doesn't name any security. On the left you have all of the \"\"bids\"\" to buy this security, on the right you have the \"\"asks\"\" to sell the security. In the middle you have the bid/ask spread, this is the space between the highest bid and the lowest ask. As you can see you are free to place you order to the market to buy for 232, and someone else is free to place their order to the market to sell for 234. When the bid and the ask match there's a transaction for the maximum number of available shares. Alternatively, someone can place a market order to buy or sell and they'll just take the current market price. Retail investors don't really get access to this kind of chart from their brokers because for the most part the information isn't terribly relevant at the retail level.\"", "title": "" }, { "docid": "78138", "text": "\"It depends on many factors, but generally, the bid/ask spread will give you an idea. There are typically two ways to buy (or sell) a security: With a limit order, you would place a buy for 100 shares at $30-. Then it's easy, in the worst case you will get your 100 shares at $30 each exactly. You may get lucky and have the price fall, then you will pay less than $30. Of course if the price immediately goes up to say $35, nobody will sell at the $30 you want, so your broker will happily sit on his hands and rake in the commission while waiting on what is now a hail Mary ask. With a market order, you have the problem you mention: The ticker says $30, but say after you buy the first 5 shares at $30 the price shoots up and the rest are $32 each - you have now paid on average $31.9 per share. This could happen because there is a limit order for 5 at $30 and 200 at $32 (you would have filled only part of that 200). You would be able to see these in the order book (sometimes shown as bid/ask spread or market depth). However, the order book is not law. Just because there's an ask for 10k shares at $35 each for your $30 X stock, doesn't mean that by the time the price comes up to $35, the offer will still be up. The guy (or algorithm) who put it up may see the price going up and decide he now wants $40 each for his 10k shares. Also, people aren't obligated to put in their order: Maybe there's a trader who intends to trade a large volume when the price hits a certain level, like a limit order, but he elected to not put in a limit order and instead watch the ticker and react in real time. Then you will see a huge order suddenly come in out of nowhere. So while the order book is informative, what you are asking is actually fundamentally impossible to know fully, unless you can read the minds of every interested trader. As others said, in \"\"normal\"\" securities (meaning traded at a major exchange, especially those in the S&P500) you simply can't move the price, the market is too deep. You would need millions of dollars to budge the price, and if you had that much money, you wouldn't be asking here on a QA site, you would have a professional financial advisor (or even a team) that specializes in distributing your large transaction over a longer time to minimize the effect on the market. With crazier stocks, such as OTC and especially worthless penny stocks with market caps of $1 mil or less, what you say is a real problem (you can end up paying multiples of the last ticker if not careful) and you do have to be careful about it. Which is why you shouldn't trade penny stocks unless you know what you're doing (and if you're asking this question here, you don't).\"", "title": "" }, { "docid": "186392", "text": "This is too lengthy for a comment. The following quoted passages are excerpted from this Money SE post. Before electronic trading and HFTs specifically, trading was thin and onerous. No. The NYSE and AMEX were deep, liquid and transparent for nearly 75 years prior to high frequency trading (HFT), in 2000 or so. The same is true for NASDAQ, but not for as many years, as NASDAQ is newer, being an electronic market. The point is that it existed, and thrived, prior to HFT. The NASDAQ can be active and functional, WITH or WITHOUT high frequency trading. This is not historically true, nor is it true now: Without a bid or ask at any given time, there could be no trade... Market makers, also known as specialists, were responsible for hitting the bid and taking the offer on whatever security they covered. They had a responsibility assigned to them by the exchange. Yes, it was lucrative! There was risk, and they were rewarded for bearing it. There is a trade-off though. Specialists provided greater stability on a systemic level, although other market participants paid for that cost. Prior to HFT, traders who were not market makers were often bounded by, boxed in, by the toll paid to market makers. Market makers had different, much higher capital and solvency requirements than other traders. Most specialists/market makers had seats, or shared a seat on the NYSE or AMEX. Remember that market makers/specialists are specific to stock markets, whereas HFT is not. If this is true, then we are in trouble: HFTs have supplanted the traditional market maker Why? Because trading volume is LOWER now than it was in the 1990's! EDIT In the comments, I noticed that OP was asking about the difference between I suggest reading this very accurate, well-written answer to a related question, The spread goes to the market maker, is the market maker the exchange? That explains the difference between", "title": "" }, { "docid": "112714", "text": "\"Market makers (shortened MM) in an exchange are generally required to list both a bid and ask price to allow both buyers and sellers to trade and keep the market moving. However, a more general idea of a MM may includes companies off an exchange (say large banks acting as broker/dealers in an over-the-counter market) are not required to give a simultaneous bid/ask, but often will on request. So, it might depend on where you are getting this data but likely the bid/ask was quoted simultaneously. An exchange, like the NASDAQ for instance, may have multiple MMs for a given market. The \"\"market\"\" spread will be from the highest bid to the lowest ask over all the MMs. The highest bid and lowest ask may come from different MMs and any particular MM often will have a larger spread. The size of the spread gives a rough idea of how much a MM is trying to make off of a \"\"round trip\"\" trade (buying than immediately selling to someone else or selling than immediately buying from someone else). Of course, immediate round-trip trades are not always possible and there are many other complications. However, half the spread is a rough indicator of how much they hope to make off of a single trade.\"", "title": "" }, { "docid": "580364", "text": "\"This is a misconception. One of the explanations is that if you buy at the ask price and want to sell it right away, you can only sell at the bid price. This is incorrect. There are no two separate bid and ask prices. The price you buy (your \"\"bid\"\") is the same price someone else sells (their \"\"sell\"\"). The same goes when you sell - the price you sell at is the price someone else buys. There's no spread with stocks. Emphasized it on purpose, because many people (especially those who gamble on stock exchange without knowing what they're doing) don't understand how the stock market works. On the stock exchange, the transaction price is the match between the bid price and the ask price. Thus, on any given transaction, bid always equals ask. There's no spread. There is spread with commodities (if you buy it directly, especially), contracts, mutual funds and other kinds of brokered transactions that go through a third party. The difference (spread) is that third party's fee for assuming part of the risk in the transaction, and is indeed added to your cost (indirectly, in the way you described). These transactions don't go directly between a seller and a buyer. For example, there's no buyer when you redeem some of your mutual fund - the fund pays you money. So the fund assumes certain risk, which is why there's a spread in the prices to invest and to redeem. Similarly with commodities: when you buy a gold bar - you buy it from a dealer, who needs to keep a stock. Thus, the dealer will not buy from you at the same price: there's a premium on sale and a discount on buy, which is a spread, to compensate the dealer for the risk of keeping a stock.\"", "title": "" }, { "docid": "7796", "text": "\"Okay, so... > Lifting* the offer (hit bids, lift offers). And I suppose that's a stategy, albeit a somewhat simple one. Passive routing strategies differ from firm to firm and algo to algo. What is your customer going to think if you bid up a new price level only for the stock to rally completely away from it? I mean if you have an open order for more than 10 times the amount currently offered with a limit above the offer, and you havent gotten filled on the bid, what can you do but lift the offer and try to be first at the next price level up? At least you would have gotten some at the price they quoted, or are they fill or kill? > \"\"Bidding it up to attract sellers\"\" sounds an awful lot like spoofing, just a heads up. Sure though, if you want to tighten a spread or create new levels with aggressive passive liquidity, that is a strategy. The same caveats as I mentioned above apply. Just to be clear, 'aggressively adding passive liquidity' is the more apt way to put it - I'm talking about when you actually want to get filled on those bids but you're having trouble finding sellers. Could you give me an example of what you might consider passive or aggressive, just for scale - would a mkt impact of .10% raise any eyebrows? How do you gauge fair value or does that matter less to you than just accumulating/selling what you can for what you were asked to? > Anyway, if market impact isn't an issue for the customer, sure, take liquidity until you're filled. Don't forget about getting good size done in the opening and closing auctions (MOO/MOC). If you're too passive you risk the market moving away from you and pissing off the customer. If you're too aggressive you risk moving the market too much and pissing off the customer. So then is the question more 'how motivated is the buyer or seller?' I'm glad you bring up the MOO/MOC, are there certain securities that don't have much of a market in those auctions? Trying to suss out how a large firm can hold a position in some of the less popular names with next to no liquidity and little in the way of dark pool, auction, block sales, etc.\"", "title": "" }, { "docid": "375161", "text": "A couple ways, but its not a guarantee. You have to have special charts. Instead of each tick being 1 min, 5 min, or whatever, it is a set number of trades. Say 2000. Since retail investors only buy and sell in small amounts, there will be small volume per tick. An institutional investor, however, would have a much much higher trade lot size, even if using an algo. Thus, large volume spikes in such a chart would signal institutional activity over retail. Similarly, daily charts showing average trade size can help you pick out when institutional activity is highest, as they have much larger trade sizes. You could also learn how the algos work and look for evidence one is being used. ie every time price hits VWAP a large sell order goes through would indicate an institutional investor is selling, especially if it happens multiple times in a row.", "title": "" }, { "docid": "269043", "text": "If you are restricting yourself to Scotiabank (Both retail banking and iTrade), your choices are pretty limited. If you are exchanging more than CAD$25,000 to EUR without margin, you can call Scotiabank and ask for a quote with much lower spread than the published snapshots. The closest ETF that you are talking about is RWE.B on TSX, which is First Asset MSCI Europe Low Risk Weighted ETF (Unhedged). You will be exposed to huge equity market risk and you should do it only if you intend to hold it for 3-5 years. Another way of exchanging cash is without opening an account is through a currency exchange broker (search “toronto currency exchange” for relevant companies). First you send an email asking for a quote for the amount you wanted, then you send the CAD to them via cheque, and they would convert to EUR and deposit it to your EUR account at Scotiabank (retail banking). This method costs around 0.7% compared to 2.5% charged by Scotiabank. An example of these brokers is Interchange Currency Exchange in Toronto. If you are hedging more than 125000 EUR, the proper method is to open an account that supports trading Currency Futures on Globex (US CME group). You can long Euro/Canadian Dollar Futures on margin. The last method is to open an account at Interactive Brokers, put CAD in it, then borrow more CAD to buy EUR. This method costs a few dollars upon trading and the spread is negligible. You need to pay 2.25% per year margin interest through.", "title": "" }, { "docid": "216823", "text": "Lowered bid ask spread. If you as a market market have to onto inventory (risk) for a long period then you have to charge your customers a commensurate premium. The groups who have lost because of HFT are big banks, any large investor who used to get preferential treatment from brokers, and floor traders. The groups who have won are retail investors and those investors who weren't large or connected enough to get preferential treatment from brokers (majority of investors).", "title": "" }, { "docid": "505244", "text": "\"- In a quote driven market, must every investor trade with a market maker? In other words, two parties that are both not market makers cannot trade between themselves directly? In a way yes, all trades go through a market maker but those trades can be orders put in place by a \"\"person\"\" IE: you, or me. - Does a quote driven market only display the \"\"best\"\" bid and ask prices proposed by the market makers? In other words, only the highest bid price among all the market makers is displayed, and other lower bid prices by other market makers are not? Similarly, only the lowest ask price over all market makers is displayed, and other higher ask prices by other market makers are not? No, you can see other lower bid and higher ask prices. - In a order-driven market, is it meaningful to talk about \"\"the current stock price\"\", which is the price of last transaction? Well that's kind of an opinion. Information is information so it won't be bad to know it. Personally I would say the bid and ask price is more important. However in the real world these prices are changing constantly and quickly so realistically it is easier to keep track of the quote price and most likely the bid/ask spread is small and the quote will fall in between. The less liquid a security is the more important the bid/ask is. -- This goes for all market types. - For a specific asset, will there be several transactions happened at the same time but with different prices? Today with electronic markets, trades can happen so quickly it's difficult to say. In the US stock market trades happen one at a time but there is no set time limit between each trade. So within 1 second you can have a trade be $50 or $50.04. However it will only go to $50.04 when the lower ask prices have been exhausted. - Does an order driven market have market makers? By definition, no. - What are some examples of quote driven and order driven financial markets, in which investors are commonly trading stocks and derivatives, especially in U.S.? Quote driven market: Bond market, Forex. Order driven market: NYSE comes from an order driven market but now would be better classified as a \"\"hybird market\"\" Conclusion: If you are asking in order to better understand today's stock markets then these old definitions of Quote market or Order market may not work. The big markets in the real world are neither. (IE: Nasdaq, NYSE...) The NYSE and Nasdaq are better classified as a \"\"hybird market\"\" as they use more then a single tactic from both market types to insure market liquidity, and transparency. Markets these days are strongly electronic, fast, and fairly liquid in most cases. Here are some resources to better understand these markets: An Introduction To Securities Markets The NYSE And Nasdaq: How They Work Understanding Order Execution\"", "title": "" }, { "docid": "494727", "text": "\"Re: A trader when buying needs to buy at the ask price and when selling needs to sell at the bid price. So how can a trade happen 'in between' the bid and ask? Saying the trade can happen \"\"in between\"\" the bid & ask is simplistic. There is a time dimension to the market. It's more accurate to say that an order can be placed \"\"in between\"\" the current best bid & ask (observed at time T=0), thus establishing a new level for one or the other of those quoted prices (observed at time T>0). If you enter a market order to buy (or sell), then yes, you'll generally be accepting the current best ask (or best bid) with your order, because that's what a market order says to do: Accept the current best market price being offered for your kind of transaction. Of course, prices may move much faster than your observation of the price and the time it takes to process your order – you're far from being the only participant. Market orders aside, you are free to name your own price above or below the current best bid & ask, respectively. ... then one could say that you are placing an order \"\"in between\"\" the bid and ask at the time your order is placed. However – and this is key – you are also moving one or the other of those quoted prices in the process of placing your above-bid buy order or your below-ask sell order. Then, only if somebody else in the market chooses to accept your new ask (or bid) does your intended transaction take place. And that transaction takes place at the new ask (or bid) price, not the old one that was current when you entered your order. Read more about bid & ask prices at this other question: (p.s. FWIW, I don't necessarily agree with the assertion from the article you quoted, i.e.: \"\"By looking for trades that take place in between the bid and ask, you can tell when a strong trend is about to come to an end.\"\" I would say: Maybe, perhaps, but maybe not.)\"", "title": "" } ]
2830	Is there any instrument with real-estate-like returns?	[ { "docid": "206368", "text": "", "title": "" }, { "docid": "113189", "text": "Similarly to buying property on your own, REITs cannot get to good returns without leveraging. If you buy an investment property 100% cash only - chances are that 10% ROI is a very very optimistic scenario. If you use leveraging (i.e.: take out a mortgage) - you're susceptible to interest rate changes. REITs invest in properties all around all the time. They invest in mortgages themselves as well (In the US, that's the only security REITs can hold without being disqualified). You can't expect all that to be cash-only, there have to be loans and financing involved. When rates go up - financing costs go up. That brings net income down. Simple math. In the US, there's an additional benefit to investing in REIT vs directly holding real estate: taxes. REITs pay dividends, which have preferential (if qualified) taxation. You'll pay capital gains taxes on the dividends if you hold the fund long enough. If you own a rental property directly, your income after all the expenses is taxed at ordinary rates, which would usually be higher. Also, as you mentioned, you can use them as margin, and they're much much more liquid than holding real estate directly. Not to mention you don't need to deal with tenants or periods where you don't have any, or if local real-estate market tanks (while REITs are usually quite diversified in kinds of real estate they hold and areas). On the other hand, if you own real estate, you can leverage it at lower rates than margin (with HELOCs etc), and it provides some safety net in case of a stock market crash (which REITs are somewhat susceptible to). You can also live in your property, if needed, which is something that's hard to do with REITs....", "title": "" } ]	[ { "docid": "375965", "text": "There is a subprime loaning bubble in the auto loan sector which is growing; while it's not in the $1 trillion range or as hidden as the real estate one was, it could cause issues down the road if it continues. The use of derivatives or specifically, CDS, is continuing for other suspect investments. It was used about 4 years ago to help hide Greece's sovereign default and like in 2008, it allowed the bad debt to be hidden and thrive to dangerous levels. The use isn't widespread and limited to several firms so far, but its return as an instrument of choice so soon after the financial crisis is a little worrying that it may be a cyclical crisis.", "title": "" }, { "docid": "482077", "text": "\"leverage amplifies gains and losses, when returns are positive leverage makes them more positive, but when returns are negative leverage makes them more negative. since most investments have a positive return in \"\"the long run\"\", leverage is generally considered a good idea for long term illiquid investments like real estate. that said, to quote keynes: in the long run we are all dead. in the case of real estate specifically, negative returns generally happen when house prices drop. assuming you have no intention of ever selling the properties, you can still end up with negative returns if rents fall, mortgage rates increase or tax rates rise (all of which tend to correlate with falling property values). also, if cash flow becomes negative, you may be forced to sell during a down market, thereby amplifying the loss. besides loss scenarios, leverage can turn a small gain into a loss because leverage has a price (interest) that is subtracted from any amplified gains (and added to any amplified losses). to give a specific example: if you realize a 0.1% gain on x$ when unleveraged, you could end up with a 17% loss if leveraged 90% at 2% interest. (gains-interest)/investment=(0.001x-0.020.9x)/(x/10)=-0.01710=-0.17=17% loss one reason leveraged investments are popular (particularly with real estate), is that the investor can file bankruptcy to \"\"erase\"\" a large negative net worth. this means the down side of a leveraged investment is limited for the highly leveraged investor. this leads to a \"\"get rich or start over\"\" mentality common among the self-made millionaire (and failed entrepreneurs). unfortunately, this dynamic also leads to serious problems for the banking sector in the event of a large nation-wide devaluation of real estate prices.\"", "title": "" }, { "docid": "190385", "text": "\"No, it can really not. Look at Detroit, which has lost a million residents over the past few decades. There is plenty of real estate which will not go for anything like it was sold. Other markets are very risky, like Florida, where speculators drive too much of the price for it to be stable. You have to be sure to buy on the downturn. A lot of price drops in real estate are masked because sellers just don't sell, so you don't really know how low the price is if you absolutely had to sell. In general, in most of America, anyway, you can expect Real Estate to keep up with inflation, but not do much better than that. It is the rental income or the leverage (if you buy with a mortgage) that makes most of the returns. In urban markets that are getting an influx of people and industry, however, Real Estate can indeed outpace inflation, but the number of markets that do this are rare. Also, if you look at it strictly as an investment (as opposed to the question of \"\"Is it worth it to own my own home?\"\") there are a lot of additional costs that you have to recoup, from property taxes to bills, rental headaches etc. It's an investment like any other, and should be approached with the same due diligence.\"", "title": "" }, { "docid": "112271", "text": "I would go with the 2nd option (put down as little as possible) with a small caveat: avoid the mortgage insurance if you can and put down 20%. Holding your rental property(ies)'s mortgage has some benefits: You can write off the mortgage interest. In Canada you cannot write off the mortgage interest from your primary residence. You can write off stuff renovations and new appliances. You can use this to your advantage if you have both a primary residence and a rental property. Get my drift? P.S. I do not think it's a good time right now to buy a property and rent it out simply because the housing prices are over-priced. The rate of return of your investment is too low. P.S.2. I get the feeling from your question that you would like to purchase several properties in the long-term future. I would like to say that the key to good and low risk investing is diversification. Don't put all of your money into one basket. This includes real estate. Like any other investment, real estate goes down too. In the last 50 or so years real estate has only apprepriated around 2.5% per year. While, real estate is a good long term investment, don't make it 80% of your investment portfolio.", "title": "" }, { "docid": "217478", "text": "\"The loan is the loan, the down payment is not part of the loan. The principle amount owed on the loan at the beginning of the loan is the amount of the loan. If your loan amount is $390,000 then that's below the \"\"jumbo\"\" classification. Your down payment is irrelevant. Lenders may want or require 20% (or any other amount) down so the loan will meet certain \"\"loan to value\"\" ratio requirements. In the case of real estate the lenders in general want a 20% down side cushion before you're \"\"upside down\"\" (owe more than the home is worth). This is not unique to homes and is common in many secured lending instruments; like cars for example.\"", "title": "" }, { "docid": "390751", "text": "\"A REIT is a real estate investment trust. It is a company that derives most of its gross income from and holds most of its assets in real estate investments, which, in this case, include either real property, mortgages, or both. They provide a way for investors to get broad exposure in a real estate market without going to buy a bunch of properties themselves. It also provides diversification within the real estate segment since REITs will often (but not necessarily) have either way more properties than an individual could get or have very large properties (like a few resorts) that would be too expensive for any one investor. By law, they must pay at least 90% of their taxable income as dividends to investors, so they typically have a good dividend rate (possibly but not necessarily) at the expense of growth of the stock price. Some of those dividends may be tax advantaged and some will not. An MLP is a master limited partnership. These trade on the exchange like corporations, but they are not corporations. (Although often used in common language as synonyms, corporation and company are not the same thing. Corporation is one way to organize a company under the law.) They are partnerships, and when you buy a share you become a partner in the company. This is an alternative form of ownership to being a shareholding. In this case you are a limited partner, which means that you have limited liability as with stock. The shares may appreciate or not, just like a stock, and you can generally sell them back to the market for a capital gain or loss under the same rules as a stock. The main difference here from a practical point of view is taxes: Partnerships (of any type) do no pay tax - Instead their income and costs are passed to the individual partners, who must then include it on their personal returns (Form 1040, Schedule E). The partnership will send each shareholder a Schedule K-1 form at tax time. This means you may have \"\"phantom income\"\" that is taxable even though cash never flowed through your hands since you'll have to account for the income of the partnership. Many partnerships mitigate this by making cash distributions during the year so that the partners do actually see the cash, but this is not required. On the other hand, if it does happen, it's often characterized as a return of capital, which is not taxable in the year that you receive it. A return of capital reduces your cost basis in the partnership and will eventually result in a larger capital gain when you sell your shares. As with any investment, there are pros and cons to each investment type. Of the two, the MLP is probably less like a \"\"regular\"\" stock since getting the Schedule K-1 may require some extra work at tax time, especially if you've never seen one before. On the other hand, that may be worth it to you if you can find one that's appreciating in value and still returning capital at a good rate since this could be a \"\"best of everything\"\" situation where you defer tax and - when you eventually do pay, you pay at favorable capital gains rates - but still manage to get your cash back in hand before you sell. (In case not clear, my comments about tax are specific to the US. No idea how this is treated elsewhere.) By real world example, I guess you meant a few tickers in each category? You can find whole lists online. I just did a quick search (\"\"list of MLP\"\" and \"\"list of REIT\"\"), found a list, and have provided the top few off of the first list that I found. The lists were alphabetical by company name, so there's no explicit or implicit endorsement of these particular investments. Examples of REIT: Examples of MLP:\"", "title": "" }, { "docid": "80797", "text": "My equities portfolio breaks down like this: (I'm 26 years old, so it is quite aggressive) Additionally, I have a portfolio of direct real estate investments I have made over the past 4 years. I invested very aggressively into real estate due to the financial crisis. As a result of my aggressive investing & strong growth in real estate, my overall asset breakdown is quite out of balance. (~80% Real Estate, ~20% Equities) I will be bringing this into a more sensible balance over the next few years as I unwind some of my real estate investments & reinvest the proceeds into other asset classes. As for the alternative asset groups you mentioned, I looked quite seriously at Peer to Peer lending a few years back. (Lending Club) However, interest rates were quite low & I felt that Real Estate was a better asset class to be in at the time. Furthermore, I was borrowing heavily to fund real estate purchases at the time, and I felt it didn't make much sense to be lending cash & borrowing at the same time. I needed every dime I could get a hold of. :) I will give it another look once rates come back up. I've shied away from investing in things like actively managed mutual funds, hedge funds, etc ... not because I don't think good managers can get superior returns ... rather, in my humble opinion, if they DO get above average returns then they simply charge higher management fees to reflect their good performance. Hope this helps!", "title": "" }, { "docid": "523310", "text": "I rather like The Ascent of Money, by Niall Ferguson. This comes in several formats. There's a video version, a written version (ISBN-13: 978-1594201929), and an audio version. This book covers the history of financial instruments. It covers the rise of money, the history of bonds and stocks, insurance and hedge funds, real-estate, and the spread of finance across the world. It is a great introduction to finance, though its focus is very definitely on the history. It does not cover more advanced topics, and will not leave you with any sort of financial plan, but it's a great way to get a broad overview and historical understanding of money and markets. I strongly recommend both the video and the written or audio version.", "title": "" }, { "docid": "108081", "text": "I don't think the location of the funds is any of your concern. You're buying a CDI, which is: Australian financial instruments The US has no jurisdiction over you, being you an Australian, so unless you own a US-based asset (i.e.: a real-estate in the US, or a US brokerage account), US tax laws shouldn't matter to you.", "title": "" }, { "docid": "509197", "text": "\"There are five main drivers to real estate returns: Income (cash flow from rental payments); Depreciation (as an expense that can be used to reduce taxes); Equity (the gradual paydown of the mortgage the increases underlying equity in the property); Appreciation (any increase in the overall value of the property); Leverage (the impact of debt financing on the deal, increasing the effective \"\"cash-on-cash\"\" return). (Asset Rover has a detailed walk-through of the components, and a useful comparison to stocks) So interest rates are certainly a component (as they increase the expenses), but they are just one factor. Depending on a particular market's conditions, appreciation or rent increases could offset or (exceed) any increase in the interest expense. My own experience is mostly with non-listed REITs (including Reg A+ investments like the ones from Fundrise) and commercial syndicates, and for right now in both cases there's plenty of capital chasing yield to go around (and in fact competition among new funding sources like Reg D and Reg A+ platforms seems to be driving down borrowing rates as platforms compete both for borrowers and for investors). Personally I pay more attention to where each local market (and the broader national market) is along the ~18-year real estate cycle (spoiler: the last trough was 2008...). Dividend Capital puts out a quarterly report that's super useful.\"", "title": "" }, { "docid": "578597", "text": "You apparently assume that pouring money into a landlord's pocket is a bad thing. Not necessarily. Whether it makes sense to purchase your own home or to live in a rental property varies based on the market prices and rents of properties. In the long term, real estate prices closely follow inflation. However, in some areas it may be possible that real estate prices have increased by more than inflation in the past, say, 10 years. This may mean that some (stupid) people assume that real estate prices continue to appreciate at this rate in the future. The price of real estates when compared to rents may become unrealistically high so that the rental yield becomes low, and the only reasonable way of obtaining money from real estate investments is price appreciation continuing. No, it will not continue forever. Furthermore, an individual real estate is a very poorly diversified investment. And a very risky investment, too: a mold problem can destroy the entire value of your investment, if you invest in only one property. Real estates are commonly said to be less risky than stocks, but this applies only to large real estate portfolios when compared with large stock portfolios. It is easier to build a large stock portfolio with a small amount of money to invest when compared to building a large real estate portfolio. Thus, I would consider this: how much return are you going to get (by not needing to pay rent, but needing to pay some minor maintenance costs) when purchasing your own home? How much does the home cost? What is the annual return on the investment? Is it larger than smaller when compared to investing the same amount of money in the stock market? As I said, an individual house is a more risky investment than a well-diversified stock portfolio. Thus, if a well-diversified stock portfolio yields 8% annually, I would demand 10% return from an individual house before considering to move my money from stocks to a house.", "title": "" }, { "docid": "419926", "text": "\"Real Estate has historically been the most sound investment of all times. Not only does property consistant increase in value (which is what you want every investment to do), it does so at the highest rate with the lowest risk. Most return on investment (like a stock in the market) the potential rate of gain is proportionat to the potential loss. The more secure an investment, the lower the potential gain. But, with Real Estate, property typically doubles in value every 10 years. Our overall R.E. economy is on an upward turn, recovering from a time where values tanked. to jump in now, is probably better than waiting for any amount of time, be it 1 month, or 1 year. You concern about being \"\"tied in\"\" to this investment is a valid concern, however, since the market is in an upward turn, you should be more and more able to turn around and sell it later on. The best thing that you could potentially do would be to invest in a rental property where your cost of investment (your mortgage note) is paid by the renters. However, being a landlord is always a risky business (hence, the higher rate of return, which considering your investment is ultimately zero, the return rate is huge :-) The trick would be to take the reters payments to you and keep it in an account that you use to pay for any repairs, upgrades, or marketing in between when the unit is vacant. But, with your parents losing their house, this may not be possible - unless you take their home and then keep the living arrangments the same as they are now. One possibility to help you get your foot in the door of being a property owner (not necessarily \"\"investor\"\") and help your parents keep their house (if that is what they would like to do) is re-finance with them... if you can't afford the entire mortgage, but they are capable of filling the gap between what you can afford and what their property costs, then you become partnered with them, and when/if their circumstances change, they can always buy you out.\"", "title": "" }, { "docid": "124230", "text": "A general rule of thumb is to avoid having more than 5% of your investments in any single stock, to avoid excessive risk; it's usually even more risky if you're talking company stock because an adverse event could result in an inferior stock price and you getting laid off. Under other circumstances, the ideal amount of company stock is probably 0%. But there are tax benefits to waiting, as you've noted, and if you're reasonably confident that the stock isn't likely to jerk around too much, and you have a high risk tolerance (i.e. lots of extra savings besides this), and you're comfortable shouldering the risk of losing some money, it might make sense to hold onto the stock for a year - but never any longer. The real risk to holding a lot of company stock doesn't depend on how often you buy it and sell it per se, but having period purchases every month should make it easier for you to ladder the funds, and regularly sell your old shares as you purchase new shares. You might also consider a stop-loss order on the stock at or near the price you purchased it at. If the stock is at $100, then you buy at $85, and then the stock drops to $85, there are no more outstanding tax benefits and it makes no sense to have it as part of your portfolio instead of any other speculative instrument - you probably get better diversification benefits with any other speculative instrument, so your risk-adjusted returns would be higher.", "title": "" }, { "docid": "217242", "text": "You could look into an index fund or ETF that invests primarily in Real Estate Investment Trusts (REIT's). An REIT is any corporation, trust or association that acts as an investment agent specializing in real estate and real estate mortgages Many investment firms offer an index fund or ETF like this. For example, Vanguard and Fidelity have funds that invest primarily in real estate markets. You could also invest in a home construction ETF, like iShares' ITB, which invests in companies related to home construction. This ETF includes more companies than just REITs, so for example, Home Depot is included.", "title": "" }, { "docid": "80519", "text": "\"Frequently selling and buying properties is generally not advisable in Germany due to the high cost for property purchase tax (\"\"Grunderwerbssteuer\"\") and land registration fees (\"\"Grundbucheintrag\"\"). You can generally assume that ever time you trade homes, you pay about 10% extra. So it is likely a good idea to keep your property and rent it out while you don't need it so you can use the rent to pay for your new room. That's especially true if you expect the property to increase in value. Also, due to the low interest rate right now, real estate is practically the only good capital investment. A 85k asset which makes you 4.8k each year is a return of investment of 5.6%. Any financial asset promising you that kind of dividend at the moment is likely equivalent to gambling. yes, I ignored maintenance costs, but it's still a really good deal. If you want to rent out your flat as stress-free as possible, give it to a property management company (\"\"Hausverwalter\"\"). In exchange for a percentage of the monthly rent they will take care of all the small stuff (like hiring handymen to fix broken toilets). You might still have to pay for really expensive investments, though (like replacing a leaking roof). But when something like that happens, you should have no issue to finance it with a loan because you have a real estate as a security. However, keep in mind that the German tenancy law might make it difficult (but not impossible) to get rid of the tenant in case you want to move back into the apartment. Google \"\"Mietrecht Eigenbedarf\"\" for more details. Should you decide after your study that you don't want to move back, you can always sell the flat with the tenant. But rented properties usually get far lower prices on the real estate market than empty ones. Regarding covering your cost of living besides rent during your studies: If you are eligible for BAföG (state-sponsored student loan), you should take it, because it's an offer simply too good to refuse. It's literally free money. But unfortunately you are not, because you own too much real estate wealth you are not living in. But you should ask your bank for a loan backed by said property. That way you will likely pay far less interest than with a regular private student loan which isn't backed by anything except the hope for a relevant degree.\"", "title": "" }, { "docid": "387141", "text": "Well, Taking a short position directly in real estate is impossible because it's not a fungible asset, so the only way to do it is to trade in its derivatives - Investment Fund Stock, indexes and commodities correlated to the real estate market (for example, materials related to construction). It's hard to find those because real estate funds usually don't issue securities and rely on investment made directly with them. Another factor should be that those who actually do have issued securities aren't usually popular enough for dealers and Market Makers to invest in it, who make it possible to take a short position in exchange for some spread. So what you can do is, you can go through all the existing real estate funds and find out if any of them has a broker that let's you short it, in other words which one of them has securities in the financial market you can buy or sell. One other option is looking for real estate/property derivatives, like this particular example. Personally, I would try to computationally find other securities that may in some way correlate with the real estate market, even if they look a bit far fetched to be related like commodities and stock from companies in construction and real estate management, etc. and trade those because these have in most of the cases more liquidity. Hope this answers your question!", "title": "" }, { "docid": "353415", "text": "\"Another option you might consider is rolling over some of that 401K balance into a self-directed IRA or Solo 401K, specifically one with \"\"checkbook privileges\"\". That would permit you to invest directly in a property via your IRA/401K money without it being a loan, and preserving the tax benefits. (You may not be able to roll over from your current employer's 401K while still employed.) That said, regarding your argument that your loan is \"\"paying interest to yourself\"\", while that is technically true, that neglects the opportunity cost -- that money could potentially be earning a much higher (and tax-free) return if it remains in the 401K account than if you take it out and slowly repay it at a modest interest rate. Real Estate can be a great way to diversify, build wealth, and generate income, but a company match and tax-free growth via an employee sponsored retirement account can be a pretty sweet deal too (I actually recently wrote about comparing returns from having a tenant pay your mortgage on a rental property vs. saving in a retirement account on my blog -- in short, tax-free stock-market level returns are pretty compelling, even when someone else is paying your mortage). Before taking rather big steps like borrowing from a 401K or buying a rental property, you might also explore other ways to gain some experience with real estate investing, such as the new crop of REITs open to all investors under SEC Reg A+, some with minimums of $500 or less. In my own experience, there are two main camps of real estate investors: (1) those that love the diversification and income, but have zero interest in active management, and (2) those that really enjoy real estate as a lifestyle and avocation, happy to deal with tenant screening and contractors, etc. You'll want to be careful to be sure which camp you're in before signing on to active investment in a specific property.\"", "title": "" }, { "docid": "332064", "text": "It looks like you need a lot more education on the subject. I suggest you pick up a book on investing and portfolio management to get a first idea. Dividend yields are currently way below 5% on blue chips. Unlike coupons from fixed income instruments (which, in the same risk category, pay a lot less), dividend yields are not guaranteed and neither is the invested principal amount. In either case, your calculation is far away from reality. Sure, there are investments (such as the mentioned direct investments in companies or housings in emerging economies) that can potentially earn you two digit percentage returns. Just remember: risk always goes both ways. A higher earning potential means higher loss potential. Also, a direct investment is a lot less liquid than an investment on a publicly quoted high turnover market place. If you suddenly need money, you really don't want to be pressed to sell real estate in an emerging market (keyword: bid ask spread). My advice: the money that you can set aside for the long term (10 years plus), invest it in stock ETFs, globally. Everything else should be invested in bond funds or even deposits, depending on when you will need the access. As others have pointed out, consider getting professional advice.", "title": "" }, { "docid": "429215", "text": "I'm surprised to even hear this question with the current state of devaluation of real estate. One thing I'll add to the other answers is to make sure you are doing a true apples/apples comparison to other investments when considering real estate. You can't just take subtract the purchase price from the sales price to get your ROI. Real estate has very heavy carry costs that you need to factor into any ROI calculation including: One more point: A house that you live in shouldn't be considered an investment, but rather an expense. You have to be able to liquidate an investment and collect your return. Unless you plan to move back in with your parents, you are always going to need a place to live so you can never really cash out on that investment, except perhaps by downgrading your lifestyle or a reverse mortgage.", "title": "" }, { "docid": "528206", "text": "\"Rather than thinking of becoming a landlord as a passive \"\"investment\"\" (like a bank account or mutual fund), it may be useful to think of it as \"\"starting a small part-time business\"\". While certainly many people can and do start their own businesses, and there are many success stories, there are many cases where things don't work out quite as they hoped. I wouldn't call starting any new business \"\"low risk\"\", even one that isn't expected to be one's main full-time job, though some may be \"\"acceptable risk\"\" for your particular circumstances. But if you're going to start a part-time business, is there any particular reason you'd do so in real estate as opposed to some other activity? It sounds like you'd be completely new to real estate, so perhaps for your first business you're starting you'd want it to be something you're more familiar with. Or, if you do want to enter the real estate world (or any other new business), be sure to do a lot of research, come up with a business plan, and be prepared for the possibility of losing money as with any investment or new business.\"", "title": "" }, { "docid": "6356", "text": "Real Estate potentially has two components of profit, the increase in value, and the ongoing returns, similar to a stock appreciating and its dividends. It's possible to buy both badly, and in the case of stocks, there are studies that show the typical investor lags the market by many percent. Real estate is not a homogeneous asset class. A $200K house renting for $1,000 is a far different investment than a $100K 3 family renting for $2,000 total rents. Both exist depending on the part of the country you are in. If you simply divide the price to the rent you get either 16.7X or 4.2X. This is an oversimplification, and of course, interest rates will push these numbers in one direction or another. It's safe to say that at any given time, the ratio can help determine if home prices are too high, a bargain, or somewhere in between. As one article suggests, the median price tracks inflation pretty closely. And I'd add, that median home prices would track median income long term. To circle back, yes, real estate can be a good investment if you buy right, find good tenants, and are willing to put in the time. Note: Buying to rent and buying to live in are not always the same economic decision. The home buyer will very often buy a larger house than they should, and turn their own 'profit' into a loss. e.g. A buyer who would otherwise be advised to buy the $150K house instead of renting is talked into a bigger house by the real estate agent, the bank, the spouse. The extra cost of the $225K house is the 1/3 more cost of repair, utilities, interest, etc. It's identical to needing a 1000 sq ft apartment, but grabbing one that's 1500 sq ft for the view.", "title": "" }, { "docid": "576375", "text": "yes, i am incorporating monte carlo return scenarios for both equity and real estate. yeah there is a lot to consider in the case of the property being a condo where you have to account for property taxes as well as condo fees. the two projects have entirely different considerations and it's not like the money that is injected to one is similar to the other (very different) which is why i figured there should be differing discount rates. in any case, thanks for the discussion and suggestions.", "title": "" }, { "docid": "485243", "text": "Many people have provided very good answers to this question and all the answers provide sound advice and justification. Below are some of my thoughts on the questions that you have put forward. 1) The investment manager question: The returns on your capital for a half year has been quite low; having said that, some investments do take more than half year to show some growth. You could try talking to your investment manager and ask where your money has been deployed and why the returns are low. If there are no real explanation given forth (which would be more likely as you have mentioned your investment manager does not like to discuss your money with you) you should conside Xolorus & Pete's advice and forthwith take all your money from investment manager and park it in the bank till you figure out what to do next with it. 2) Finances are not my forte: At 22 finance is nobodies forte, it takes longer than that; however having said that, how do you know finance is actually not your forte? Being a computer science graduate you would be more than comfortable with the mathematics required for finance. You may not have looked seriously at finance till now (I assume by your statement). Once way to be certain about this would be self learning, some good books have been refered above and there are online information, courses and articles on the Internet, for example here. You could give some spare time and explore if finance interests you or not. 3) If finance interests you: Then consider the 30K as your seed fund and take a small portion of it say 2K and try out your hand at investing on your own in the instruments that you feel most comfortable and see how you fare, you are young enough to take the risk. Rest of the money you could put in other low risk instruments (that you have identified through self study) 4) If finance does not interest you: The probably you are better off with an investment manager, as observed above, it will take some time for you to identify him/her 5) On returns: As mentioned above different instruments produce returns differently, however, one question that is universally asked is how much return on an invetment shoule one expect (you were expecting more than $12 on your investment). It is a difficult question to answer as invetment returns and investment needs depend on a persons financial goals and risk taking profile. One way to have some measure is to take 15-20 years CAGR of the stock index return and reduce it by 2-3%, that is (in many cases, not all) a reasonable return expectation in medium-long term.", "title": "" }, { "docid": "387717", "text": "Real estate investment is a proven creator of wealth. Check into the history of the rich and you will find real estate investment. Starting your investment in multi-family is a great idea. It is a good way to gain experience in real estate while exponentially increasing cash flow. If you turn the properties over to a reputable property management company, your cash flow will be a little less but so will your headaches. (Expect to pay 8 - 10% of gross income.) You could start investing now by looking into discounted real estate such as foreclosures, tax sales, short sales etc while the market is still depressed. This way your return on investment should be higher. From there you could expand into land development (i.e. subdivision) or commercial investments. Commercial properties with triple net leases can be a great low-stress investment opportunity (but they take more cash upfront). Attending some local real estate investment classes would be a great idea for starters.", "title": "" }, { "docid": "159652", "text": "With out a doubt: commercial real estate. Those that have significant amounts of money, and want to make lots more usually end up investing a chunk of their portfolio in commercial real estate. Everyone finds a way to make money elsewhere, but there’s no comparison to the incentives and returns in real estate when you have tens or hundreds of millions of $ at your disposal. Have money, make money.", "title": "" }, { "docid": "232651", "text": "Well, this took some interesting facts and made some raving assumptions. Generally, I'd imagine it's more likely the Chinese capital controls and atrocious domestic savings opportunities have made any dollar denominated returns desirable and with us commercial real estate in cardiac arrest, places like toledo offer lots of great investment opportunities. I think a Chinrse city outside of Milan would be fantastic. Good knows the new money and population couldn't but help MI and fostering deeper cultural ties between one of the former great manufacturing regions and the worlds newest could benefit both.", "title": "" }, { "docid": "187571", "text": "I think you may be drawing the wrong conclusion about why you put what type of investment in a taxable vs. tax-advantaged account. It is not so much about risk, but type of return. If you're investing both tax-advantaged and taxable accounts, you can benefit by putting more tax-inefficient investments inside your tax-advantaged accounts. Some aggressive asset types, like real estate, can throw off a lot of taxable income. If your asset allocation calls for investing in real estate, holding it in a 401k or IRA can allow more of your money to remain invested, rather than having to use it to pay for taxes. And if you're holding in a Roth IRA, you get that tax free. But bonds, a decidedly non-aggressive asset, also throw off a lot of taxable income. You're able to hold them in a tax-advantaged account and not pay taxes on the income until you withdraw it from the account (or tax free in the case of a Roth account.) An aggressive stock fund that is primarily expected to provide returns via price appreciation would do well in a taxable account because there's likely little tax consequence to you until it is sold.", "title": "" }, { "docid": "529435", "text": "\"This forum is not intended to be a discussion group, but I would like to add a different perspective, especially for @MrChrister, on @littleadv's rhetorical question \"\"... estates are after-tax money, i.e.: income tax has been paid on them, yet the government taxes them again. Why?\"\" For the cash in an estate, yes, that is after-tax money, but consider other assets such as stocks and real estate. Suppose a rich man bought stock in a small computer start-up company at $10 a share about 35 years ago, and that stock is now worth $500 a share. The man dies and his will bequeaths the shares to his son. According to US tax law, the son's basis in the shares is $500 per share, that is, if the son sells the shares, his capital gains are computed as if he had purchased the shares for $500 each. The son pays no taxes on the inheritance he receives. The deceased father's last income tax return (filed by the executor of the father's will) does not list the $490/share gain as a capital gain since the father did not sell the stock (the gain is what is called an unrealized gain), and so there is no income tax due from the father on the $490/share. Now, if there is no estate tax whatsoever, the father's estate tax return pays no tax on that gain of $490 per share either. Would this be considered an equitable system? Should the government not tax the gain at all? It is worth noting that it would be possible for a government to eliminate estate taxes entirely, but instead have tax laws that say that unrealized gains on the deceased's property would be taxed (as capital gains) on the deceased's final tax return.\"", "title": "" }, { "docid": "57960", "text": "Apples and oranges. The stock market requires a tiny bit of your time. Perhaps a lot if you are interested in individual stocks, and pouring through company annual reports, but close to none if you have a mix of super low cost ETFs or index fund. The real estate investing you propose is, at some point, a serious time commitment. Unless you use a management company to handle incoming calls and to dispatch repair people. But that's a cost that will eat into your potential profits. If you plan to do this 'for real,' I suggest using the 401(k), but then having the option to take loans from it. The ability to write a check for $50K is pretty valuable when buying real estate. When you run the numbers, this will benefit you long term. Edit - on re-reading your question Rental Property: What is considered decent cash flow? (with example), I withdraw my answer above. You overestimated the return you will get, the actual return will likely be negative. It doesn't take too many years of your one per year strategy to wipe you out. Per your comment below, if bought right, rentals can be a great long term investment. Glad you didn't buy the loser.", "title": "" }, { "docid": "437614", "text": "Yes - it's called the rate of inflation. The rate of return over the rate of inflation is called the real rate of return. So if a currency experiences a 2% rate of inflation, and your investment makes a 3% rate of return, your real rate of return is only 1%. One problem is that inflation is always backwards-looking, while investment returns are always forward-looking. There are ways to calculate an expected rate of inflation from foreign exchange futures and other market instruments, though. That said, when comparing investments, typically all investments are in the same currency, so the effect of inflation is the same, and inflation makes no difference in a comparative analysis. When comparing investments in different currencies, then the rate of inflation may become important.", "title": "" } ]
5a7641405542992d0ec0606d	The movies Coraline and Scooby-Doo! and the Samurai Sword were both released in what year?	[ { "docid": "21133839", "text": "Scooby-Doo! and the Samurai Sword is a 2009 direct-to-DVD animated comedy mystery martial arts film, as well as the thirteenth entry in a series of direct-to-video animated films based upon the \"Scooby-Doo\" Saturday morning cartoon franchise. In the United States, the DVD sold 163,890 units in its first week and as of January 2014, it has sold approximately 524,725 units.", "title": "" }, { "docid": "3287436", "text": "Coraline is a 2009 American 3D dark fantasy stop-motion horror film based on Neil Gaiman's 2002 novel of the same name. It was the first feature film produced by Laika and distributed by Focus Features. The film depicts an adventurous girl finding an idealized parallel world behind a secret door in her new home, unaware that the alternate world contains a dark and sinister secret. Written and directed by Henry Selick, the film was made with Gaiman's approval and cooperation.", "title": "" } ]	[ { "docid": "7983644", "text": "Aloha, Scooby-Doo is a 2005 direct-to-video animated comedy horror mystery film, and the eighth in a series of direct-to-video animated films based upon the \"Scooby-Doo\" Saturday morning cartoons. It was released on February 8, 2005, and it was produced by Warner Bros. Animation, though it featured a copyright and logo for Hanna-Barbera Cartoons at the end. It is also Ray Bumatai's last performance before his death in October 2005. This movie, along with \"Scooby-Doo and the Cyber Chase\", were the first Scooby-Doo movies to be re-released on Blu-ray on April 5, 2011.", "title": "" }, { "docid": "28014365", "text": "Scooby-Doo! Camp Scare is a 2010 direct-to-DVD animated comedy horror-mystery film based upon the \"Scooby-Doo\" Saturday morning cartoon, and was released on September 14, 2010. The film was released seven months after the release of \"Scooby-Doo! Abracadabra-Doo\". The 15th direct-to-video \"Scooby-Doo\" film, the movie sold 53,389 units in its first week and as of January 2013, it has sold approximately 194,000 units.", "title": "" }, { "docid": "17015116", "text": "Scooby-Doo Mystery is the name of two video games released by Acclaim Entertainment and Sunsoft in 1995 based on the \"Scooby-Doo\" animated series. One of the games was released for the Super Nintendo Entertainment System and is an adventure game with platforming elements. The other title, released for the Sega Genesis is a more traditional adventure game with a point-and-click-style interface. Both were released exclusively in North America. In both games, players take control of Shaggy Rogers and Scooby-Doo, who help solve various mysteries with other members of Mystery Incorporated who serve minor roles during gameplay.", "title": "" }, { "docid": "1470589", "text": "The New Scooby-Doo Movies is an American animated mystery comedy television series produced by Hanna-Barbera for CBS. It is the second animated television series in the studio's \"Scooby-Doo\" franchise, and follows the first incarnation, \"Scooby-Doo, Where Are You!\". It premiered on September 9, 1972 and ran for two seasons on CBS as the only hour-long \"Scooby-Doo\" series. Twenty-four episodes were produced, sixteen for the 1972–73 season and eight more for the 1973–74 season.", "title": "" }, { "docid": "9885736", "text": "Chill Out, Scooby-Doo! is a 2007 direct-to-DVD animated comedy mystery film, and the eleventh in the \"Scooby-Doo\" direct-to-video film series, produced by Warner Bros. Animation (though it used a Hanna-Barbera logo and copyright at the movie's ending) which began in late 2006. It was dedicated to Iwao Takamoto, who died during the making of the film, with a September 4, 2007, release date for the DVD. It was the final direct-to-video \"Scooby-Doo\" movie that Joseph Barbera was involved with (but was not dedicated to him; instead, \"\" carried a dedication to him).", "title": "" }, { "docid": "39514158", "text": "Scooby-Doo: Behind the Scenes, also known as Those Meddling Kids, is a series of shorts that was shown on Cartoon Network in 1998 about Scooby-Doo. Each short gives behind the scenes information on how Mystery Inc. formed, and backgrounds for each member of the gang. There are eight shorts in total, each approximately one minute in length. They have been released on Scooby-Doo's Greatest Mysteries (VHS), and were listed as \"groovy Scooby-Doo extra footage!\" However, they were not released on the DVD version.", "title": "" }, { "docid": "1227572", "text": "What's New, Scooby-Doo? is an American animated sitcom mystery comedy series produced by Warner Bros. Animation for The WB television network; it is the ninth incarnation of the \"Scooby-Doo\" franchise that began with Hanna-Barbera's \"Scooby-Doo, Where Are You!\" and the first of such since the previous incarnation, \"A Pup Named Scooby-Doo\", ended in 1991. The series revives the format of \"Scooby-Doo, Where Are You!\", in which the title character and his companions, Fred Jones; Daphne Blake; Velma Dinkley and Shaggy Rogers, travel to varying locations solving mysteries; this format is modernized for \"What's New, Scooby-Doo?\", in which the characters utilize technology that did not exist at the time \"Scooby-Doo, Where Are You!\" first aired. It is the first television series in the franchise in which Frank Welker, Grey DeLisle and Mindy Cohn respectively portrayed the voices of Scooby-Doo, Daphne and Velma; and the final one in which Casey Kasem portrayed Shaggy, having originally quit the role following a dispute regarding the portrayal of the character.", "title": "" }, { "docid": "31678415", "text": "Scooby-Doo! Legend of the Phantosaur is a 2011 direct-to-DVD animated comedy mystery film; the sixteenth direct-to-video movie based upon the \"Scooby-Doo\" Saturday morning cartoons, the film was released on September 6, 2011. It premiered on Cartoon Network on September 3, 2011.", "title": "" }, { "docid": "7966219", "text": "Scooby-Doo! and the Loch Ness Monster is a 2004 direct-to-video animated comedy horror film, and the seventh direct-to-video movie based upon the \"Scooby-Doo\" Saturday morning cartoons. It was released on June 22, 2004, and it was produced by Warner Bros. Animation (although Warner Bros. had fully absorbed Hanna-Barbera Cartoons by this time, Hanna-Barbera was still credited as the copyright holder and the movie ended with an H-B logo).", "title": "" }, { "docid": "25920826", "text": "Scooby-Doo! Abracadabra-Doo is a 2010 direct-to-DVD animated comedy horror mystery fantasy film, and the fourteenth entry in a series of direct-to-video animated films based upon the \"Scooby-Doo\" Saturday morning cartoons. The film is directed by Spike Brandt and Tony Cervone. It was produced in 2009 by Warner Bros. Animation and it was released on February 16, 2010. It made its television debut on July 10, 2010 on Cartoon Network The movie performed well on iTunes, reaching the Top 10 on the Kids & Family movie charts and the Top 40 on the iTunes movie charts. The DVD sold 61,341 units in its first week and as of January 2013, it has sold approximately 433,000 units. This is also the first Scooby-Doo animated movie that featured Matthew Lillard voicing Shaggy Rogers. The animation is now in a different format, with a darker, more realistic look similar to \"Zombie Island\", \"Witch's Ghost\", and the characters are now in their original outfits and designs from the classic original \"Where Are You!\" series.", "title": "" }, { "docid": "3971835", "text": "Scooby-Doo and the Reluctant Werewolf is a 1988 animated made-for-television film produced by Hanna-Barbera for syndication as part of the \"Hanna-Barbera Superstars 10\" series. It marked Scrappy-Doo's last appearance as a protagonist in the \"Scooby-Doo\" franchise to date; he would not appear in a \"Scooby-Doo\" production again until the live-action \"Scooby-Doo\" movie in 2002, where he was the main antagonist.", "title": "" }, { "docid": "50549953", "text": "Scooby-Doo! and WWE: Curse of the Speed Demon (also known as Scooby-Doo! WrestleMania Mystery 2) is a 2016 direct-to-DVD animated comedy mystery racing film, and the twenty-seventh entry in the direct-to-video series of Scooby-Doo films. It is a co-production between Warner Bros. Animation and WWE Studios. The film is a direct sequel to \"Scooby-Doo! WrestleMania Mystery\". It premiered at the San Diego Comic-Con International on July 23, 2016, followed by a digital release on July 26, 2016. It was released on DVD on August 8, 2016 in the United Kingdom. The film was also released on both DVD and Blu-Ray on August 9, 2016 in the United States by Warner Home Video and WWE Home Video.", "title": "" }, { "docid": "7839268", "text": "\"What's New, Scooby-Doo?\" is an American animated mystery-comedy series. The show was broadcast from September 14, 2002 to July 21, 2006 on Kids WB, a Saturday morning children's programming block on The WB Television Network. This is the ninth incarnation of the \"Scooby-Doo\" franchise, and features the main characters - Fred Jones, Daphne Blake, Velma Dinkley, Shaggy Rogers and Scooby-Doo - investigating appearances of supernatural creatures.", "title": "" }, { "docid": "2616021", "text": "The Scooby-Doo and Scrappy-Doo shorts represents the fifth incarnation of the Hanna-Barbera Saturday morning cartoon \"Scooby-Doo\" series. A total of 33 half-hour episodes, each of which included three 7-minute shorts, were produced over three seasons, from 1980 to 1982 on ABC. Thirteen episodes were produced for the 1980–81 season, and seven more for the 1981-82 as segments of \"The Richie Rich/Scooby-Doo Show\". The remaining thirteen episodes were produced as segments of \"The Scooby & Scrappy-Doo/Puppy Hour\" for the 1982-83 season. Out of the 99 shorts that were produced, 86 of them feature Scooby-Doo, his nephew Scrappy-Doo and Shaggy without the rest of the Mystery Inc gang, and the other 13 only feature Scrappy-Doo and Yabba-Doo.", "title": "" }, { "docid": "4449077", "text": "Scooby-Doo! Night of 100 Frights is a third person platform game with action elements that was developed by Heavy Iron Studios and published by THQ for the PlayStation 2, GameCube and Xbox consoles. The game was first released on May 20, 2002 in North America and was released later that year in PAL regions. It is the first \"Scooby-Doo!\" video game title to come to sixth generation consoles. The game became a \"Greatest Hits\" title in 2003. The game has a follow up titled \"Scooby-Doo! Mystery Mayhem\".", "title": "" }, { "docid": "1072075", "text": "Scooby-Doo (also known as Scooby-Doo: The Movie) is a 2002 American family comedy adventure film, based on the long-running Hanna-Barbera animated television series of the same name. It is the first installment in the \"Scooby-Doo\" live-action film series, directed by Raja Gosnell, written by James Gunn, and starring Freddie Prinze Jr., Sarah Michelle Gellar, Matthew Lillard, Linda Cardellini and Rowan Atkinson. The plot revolves around Mystery Incorporated, a group of four young adults and a dog who solve mysteries, who reunite after a two-year disbandment, to investigate a mystery on a popular horror resort.", "title": "" }, { "docid": "2614286", "text": "The Scooby-Doo Show is an American animated mystery comedy series. The title of the series is an umbrella term for episodes of the third incarnation of Hanna-Barbera's \"Scooby-Doo\" franchise. A total of 40 episodes ran for three seasons, from 1976 to 1978, on ABC, marking the first \"Scooby\" series to appear on the network. Sixteen episodes were produced as segments of \"The Scooby-Doo/Dynomutt Hour\" in 1976, eight episodes were produced as segments of \"Scooby's All-Star Laff-A-Lympics\" in 1977 and sixteen episodes were produced in 1978, with nine of them running by themselves under the \"Scooby-Doo, Where Are You!\" name and the final seven as segments of \"Scooby's All-Stars\".", "title": "" }, { "docid": "4748800", "text": "Neil Fanning (born 12 April 1967) is an Australian voice actor, stuntman and actor. He is most known for voicing Scooby-Doo in both of the theatrical live-action international blockbusters, \"Scooby-Doo\" and \"\". Neil's entertainment career has spanned over 25 years and over 50 movie, television and commercial roles. Among his stunt credits are \"Daybreakers\", \"\", and \"Ghost Ship\". TV appearances include \"Sea Patrol\" and the 1998 TV movie \"Chameleon\". Neil has also performed as an actor and stuntman on shows including \"Nim's Island\", \"Peter Pan\", and \"Jackie Chan's First Strike\".", "title": "" }, { "docid": "45690388", "text": "Scooby-Doo! and the Beach Beastie is the sixth direct-to-DVD special produced by Warner Bros. Animation, based upon the \"Scooby-Doo\" Saturday morning cartoons. It was released on May 5, 2015, on the \"Scooby-Doo! 13 Spooky Tales: Surf's Up Scooby-Doo\" DVD.", "title": "" }, { "docid": "24001383", "text": "Scooby-Doo! First Frights is a 3D platform video game released in 2009. It was developed by Torus Games and published by Warner Bros. Interactive Entertainment. The game tied in with the release of Scooby-Doo! The Mystery Begins on DVD. This is the fourth Scooby-Doo game to use a laugh track.", "title": "" }, { "docid": "31871202", "text": "This is a list of \"Scooby-Doo\" characters. Scooby-Doo is an American animated franchise based around several animated television series and animated, as well as live action, movies. There are five main characters in the franchise: Scooby-Doo Shaggy Rogers, Fred Jones, Velma Dinkley, and Daphne Blake—known as \"Mystery Incorporated\". There are also several recurring characters throughout the franchise, including their parents, friends, allies, and enemies.", "title": "" }, { "docid": "18685527", "text": "Scooby-Doo and the Goblin King is a 2008 direct-to-DVD animated comedy horror fantasy film, and the twelfth in the series of \"Scooby-Doo\" direct-to-video films produced by Warner Bros. Animation (though it used a Hanna-Barbera logo at the end of the movie). It was dedicated to Paulette Oates, who helped resurrect Warner Bros. Animation in the late 1980s. All the main voice actors of Mystery, Inc. reprise their roles. The DVD was released on September 23, 2008. This is the first Scooby cartoon produced entirely without either one of the original creators, William Hanna and Joseph Barbera.", "title": "" }, { "docid": "730734", "text": "Scooby-Doo 2: Monsters Unleashed is a 2004 American family comedy adventure film, based on the animated television series, \"Scooby-Doo, Where Are You?\". It is the second installment in the \"Scooby-Doo\" live-action film series and a sequel to 2002's \"Scooby-Doo\", and was directed by Raja Gosnell, written by James Gunn and released by Warner Bros. Pictures.", "title": "" }, { "docid": "3034423", "text": "The Scooby-Doo Spooky Coaster is an enclosed steel wild mouse roller coaster located at Warner Bros. Movie World on the Gold Coast, Australia. It is based on the 2002 live action film, Scooby-Doo, which was filmed at the studio adjacent to the park at the same time the ride was being constructed.", "title": "" }, { "docid": "32510483", "text": "Scooby-Doo and the Cyber Chase is a \"Scooby-Doo\" video game based on the Warner Brothers film \"Scooby-Doo and the Cyber Chase\". The game was released for the PlayStation and Game Boy Advance in 2001. The PlayStation version became a \"Greatest Hits\" title in 2003.", "title": "" }, { "docid": "36898489", "text": "Scooby-Doo! Spooky Games is a direct-to-DVD special based upon the \"Scooby-Doo\" Saturday morning cartoons, created for the London 2012 Olympics, released on July 17, 2012. This special began a trend of bonus Scooby-Doo \"special episodes\" on various DVDs.", "title": "" }, { "docid": "49994362", "text": "Lego Scooby-Doo! Haunted Hollywood is a 2016 direct-to-DVD computer-animated comedy horror mystery film, and the twenty-sixth entry in the direct-to-video series of Scooby-Doo films, as well as the first in the series to be based on the Scooby-Doo brand of Lego. It was released on DVD, Blu-ray and digitally on May 10, 2016. The first trailer was released on February 23, 2016.", "title": "" }, { "docid": "52417029", "text": "Scooby-Doo! Shaggy's Showdown is a 2017 direct-to-DVD animated comedy mystery film, and the twenty-eighth entry in the direct-to-video series of Scooby-Doo films. It was released digitally on January 31, 2017 and was released on DVD on February 14, 2017.", "title": "" }, { "docid": "28817462", "text": "Scooby-Doo! and the Spooky Swamp is a third person platform game with action elements developed by Torus Games and published by Warner Bros. Interactive Entertainment for the PlayStation 2, Wii and Nintendo DS consoles and also for Microsoft Windows. The game was first released on September 14, 2010 in North America and was released in the following weeks in PAL regions. It is the fifth \"Scooby-Doo!\" video game title to come to sixth generation consoles. The game is a follow up to \"Scooby-Doo! First Frights\".", "title": "" }, { "docid": "2694760", "text": "Scooby-Doo! Mystery Mayhem is a video game based on the Hanna-Barbera/Warner Bros. cartoon \"Scooby-Doo\". The game was released by Artificial Mind and Movement, THQ and Warner Bros. in 2003 for the Game Boy Advance. It was later released for the PlayStation 2, GameCube, and Xbox in 2004.", "title": "" } ]
7432	Buy Php in Malaysia and sell to Philippines	[ { "docid": "293483", "text": "I noticed the buy/sell board table. Where did you notice this. Generally for a pair of currencies, there is Unit associated along with direction. The Unit is generally constant. These are only revised when there is large devaluation of a particular currency. Buying Php for MYR 8.52, Selling MYR 8.98. So in this case the Unit of PHP is 100, so Bank is Buying 100 PHP from you [you are selling PHP] and will give you MYR 8.52. If you now want to buy 100 PHP [so the Bank is selling you], you have to pay MYR 8.98. So you loose MYR 0.46 Why are they selling it way beyond the exchange rate? Why is this? As explained above, they are not. Its still within the range. The quote on internet are average price. This means before going back to Philippines, I can buy a lot of peso that I can buy and exchange it for higher price right? Generally an individual cannot make money by buying in one currency and selling in other. There are specialist who try and find arbitrage between multiple pair of currencies and make money out of it. Its a continuous process, if they start making profit, the market will react and put pressure on a pair and the prices would move to remove the arbitrage.", "title": "" }, { "docid": "226321", "text": "basically the selling (for banks) means you will exchange PHP to MYR buying simply MYR to PHP the bank will buy your MYR in exchange to PHP. and you will sell your MYR to PHP. I think it has something to do with processing fee..", "title": "" } ]	[ { "docid": "120490", "text": "Interesting piece about Philippine, but there's still work to be done, especially from the state. As the [FT pointed out last week](http://blogs.ft.com/beyond-brics/2012/10/24/the-philippines-ready-for-business/#axzz2Aczv0yBy), one need 36 days to start a business and 16 different steps. That's 32 more days than in Indonesia and 13 more steps than in Malaysia. Considering the lack of resources, such a brake on entrepreneurship isn't really what Philippine needs.", "title": "" }, { "docid": "266111", "text": "I found this interesting list https://money.usnews.com/money/blogs/on-retirement/2011/12/05/the-most-tax-friendly-places-to-retire-abroad (mirror): Argentina Belize Colombia Costa Rica Croatia Ecuador France Ireland Italy Malaysia Mexico Panama Philippines Spain Thailand Uruguay One source confirming for Philippines: http://www.investopedia.com/ask/answers/052615/what-are-financial-benefits-retiring-philippines.asp : You are exempt from income taxes on annuities and pensions", "title": "" }, { "docid": "557929", "text": ">Pyramid schemes are illegal in many countries or regions including Albania, Australia,[20][21] Austria,[22] Belgium,[23] Brazil, Canada, China,[24] Colombia,[25] Denmark, the Dominican Republic,[26] Estonia,[27] Finland,[28] France, Germany, Hong Kong,[29] Hungary, Iceland, Iran,[30] the Republic of Ireland,[31] Italy,[32] Japan,[33] Malaysia, Maldives, Mexico, Nepal, the Netherlands,[34] New Zealand,[35] Norway,[36] Peru, Philippines,[37] Poland, Portugal, Romania,[38] Russian Federation, Serbia,[39] South Africa,[40] Spain, Sri Lanka,[41] Sweden,[42] Switzerland, Taiwan, Thailand,[43] Turkey,[44] Ukraine,[45] the United Kingdom,[46] and the United States.[7] https://en.wikipedia.org/wiki/Pyramid_scheme", "title": "" }, { "docid": "579007", "text": "I think the one single answer is that the answer depends on the two countries involved and their banks' practices. To find that answer, you need to ask other expats from your country living in France and ask them for their experience. Note that most expats do not know what fees they are paying. For example, in the Philippines, the lowest fee charged still involves waiting 30 days to get your money. Specifically, I opened a US dollar savings account with the minimum of US $500 required (other rules are involved for opening a bank account), deposited a personal check drawn on my US bank account (no fee charged), and waited 30 calendar days to withdraw USD bills. The Philippines bank did not have a branch in the US, but had financial arrangements with US banks. After getting USD dollars in my hand, I walked to a nearby exchange business store (which usually offered a better daily rate than a bank, but a rate between the banks' buy and sell rates) and exchange the dollars for pesos. Note that years ago, banks did not give USD bills, when dollars were scarce in the Philippines. However, this process does not work in Thailand, due to bank rules against private individuals opening a USD account, with exceptions. And there are still fees involved. March 2017", "title": "" }, { "docid": "552138", "text": "\"The country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The US withholding tax rate on dividends is 30%, although this can be reduced to 15% if there as a tax treaty in place between the US and your country of residence. Malaysia does have a double taxation agreement with the US (see here: http://www.mida.gov.my/env3/index.php?page=double-taxation-agreement) but it is flagged as a \"\"limited\"\" agreement. You'd need to find the full text of the agreement to see whether a reduced rate of dividend withholding tax would be available in the Malaysia/US treaty. See my other answer for more details on withholding taxes and how to partially reclaim under a double tax treaty: What is the dividend tax rate for UK stock Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).\"", "title": "" }, { "docid": "326559", "text": "The link provided by DumbCoder (below) is only relevant to UK resident investors and does not apply if you live in Malaysia. I noticed that in a much older question you asked a similar question about taxes on US stocks, so I'll try and answer both situations here. The answer is almost the same for any country you decide to invest in. As a foreign investor, the country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The rate of DWT that will be withheld is unique to each country. The UK does not have any withholding tax so you will always receive the full dividend on UK stocks. The withholding tax rate for the US is 30%. Other countries vary. For most countries that do charge a withholding tax, it is possible to have this reduced to 15% if there is a double taxation treaty in place between the two countries and all of the following are true: Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).", "title": "" }, { "docid": "335287", "text": "Yup, it's for Malaysia because as I said, it's for where I'm from. Can't say the same for the rest of the world, though I don't think it's just unique to Malaysia. edit: The boycott is not unique nor originate from Malaysia, so it is quite a widespread to ever reach Malaysia.", "title": "" }, { "docid": "593621", "text": "I am a web developer by day and financial systems programmer by night. You'll need to learn a compiled language and how to scale data storage if you want to code for finance. I would suggest you learn C# or Java if you really want a decent gig programming in the finance industry. Anybody using PHP and API's to trade isn't somebody you want to work for. It will cause way more headaches than it's worth and you miss opportunities due to speed and efficiency of a language like PHP. You will hit a wall with it at some point (some problem/bug/whatever that can't be solved), and it will really bring you down when you realize it has to be re-done in another language. That being said, PHP is great for the front end (showing people the data and letting them search etc), but the core of it that grabs stats and does the calculations should be in a compiled language. PHP can also be used to quickly test ideas to see if it's worth building a full system that will scale. Basically a rough draft of the program to see if it's going to work out. Why? Well in PHP you can get things done very quickly with very little code because a large amount of libraries and functions exist and it's a very easy language to understand. But it's not efficient, and that's why you create the real deal program using C, C#, or java, or whatever. Scalability of data storage will be important to. You'll need to store a ton of information and you'll need to be able to sort/change/remove/add it quickly. Many databases already exist to do this and I see you know MySQL already a good bit. You'll need to get very familiar with it because the database is going to be your biggest bottleneck in terms of speed. It doesn't matter how well your software works if the database is taking 5 seconds to return a query. Learn to tweak MySQL, learn about MSSQL, look into Firebird. Also learn about at least one NoSQL storage solution (these databases can store a massive amount of information, but they work differently than a sql database does). I would recommend learning MongoDB if you already know PHP. It is a good transition from SQL style databases to Key Storage databases. Hope this helps...", "title": "" }, { "docid": "584242", "text": "\"1. (a) \"\"Kim Jong Un Inspects KPA Strategic Force Command\"\" by Korean Central News Agency (KCNA), originally published at http://www.kcna.kp on 15 August 2017: https://kcnawatch.co/newstream/1502749950-753062439/kim-jong-un-inspects-kpa-strategic-force-command/ Original text: https://www.reddit.com/r/worldpolitics/comments/6tqkgn/north_korean_leader_kim_jong_un_has_decided_not/dlmrnnt (b) Mirror for the submitted article: https://archive.is/G32a2 2. (a) Where is Territory of Guam, United States of America (USA)? Where is Commonwealth of the Northern Mariana Islands (CNMI), USA? \\- http://chamorrobible.org/images/chamorrobibleproject/map-west-pacific-islands-1998.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-federated-states-of-micronesia-1999.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-guam-1991.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-commonwealth-of-the-northern-mariana-islands-1989.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-oceania-2002.jpg \\- [http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-other.jpg](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-other.jpg \"\"1346 x 2020\"\") ([via](http://chamorrobible.org/gpw/gpw-201304.htm), [2013 x 3020](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-medium.jpg), [2680 x 4020](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-large.jpg), [4014 x 6021](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-huge.jpg)) Source: http://chamorrobible.org and http://chamorrobible.org/gpw/gpw.htm (b) Western Pacific Ocean sunset photographed from the International Space Station while orbiting above the Philippine Sea on 21 July 2003 at 10:17:20.420 GMT: [3032 x 1986 pixels](http://chamorrobible.org/images/photos/gpw-20050108-NASA-ISS007-E-10807-space-sunset-20030721-Pacific-Ocean-large.jpg) Source: http://chamorrobible.org/gpw/gpw-20050108.htm Via: http://chamorrobible.org/gpw/gpw-The-Great-Earthquake-and-Catastrophic-Tsunami-of-2004.htm 3. https://www.reddit.com/r/worldpolitics/comments/6nnhnl/one_of_just_17_remaining_colonies_worldwide_guam/dkasdpl 4. https://www.reddit.com/r/pics/comments/4zonlj/there_are_only_148_guam_kingfishers_known_in_the/d6xh2t9 5. https://www.reddit.com/r/environment/comments/6qqo3l/druglaced_mice_to_be_used_to_combat_brown_tree/dkz84p8 6. https://www.reddit.com/r/Anthropology/comments/6slxkq/3500_years_of_chamorro_history_its_like_an/dldpcqy 7. https://www.reddit.com/r/linguistics/comments/5b3iw1/our_language_isnt_dead_yet_by_michael_lujan/d9lfot8 8. \"\"Island Stealth: F-22A Raptors and a B-2 Spirit Over Guam, USA\"\" (Larger Version), April 2009: https://www.youtube.com/watch?v=kVP_8afut1s Source: http://chamorrobible.org/gpw/gpw-200905.htm\"", "title": "" }, { "docid": "102076", "text": "One of the many reasons why condominiums became popular in the Philippines as a modern family-home is because of its location, in which most of these types of [condo in Philippines](http://www.ayalalandpremier.com/One-serendra.php) are found outside Metro Manila, either in the outskirts or in some popular neighboring provinces surrounding the capital, such as in Tagaytay and Laguna. These types of condominiums are known as condominium complexes.", "title": "" }, { "docid": "433807", "text": "There's lots more entrepreneurship in the Philippines it's just under the radar. Big business is controlled by a handful of oligarchs. #1 problem in the Philippines would be corruption in government, IMO, followed by their bad weather/geological situation, and then terrorism. These are all huge roadblocks to overcoming poverty on their own. That difficulty to officially start a business does make things harder, and unfortunately the smarter folks who live there often find a way to put their skills to use abroad.", "title": "" }, { "docid": "563350", "text": "Masai Auto City is a good opportunity to buy the second hand used car at the affordable price. We have every car certified by our expert team. If you want to save the money to buy the car in new condition it is a perfect place for you. Now, it has been become a very popular place in Johor city. There is a lot of car dealer in Malaysia, but they haven't certified car. Locate the most Toyota companies that dependably give you the best opportunity to buy Masai used car Toyota at the moderate cost. You can sift through the chase in light of different parameters comprising Masai second hand car dealer.", "title": "" }, { "docid": "366141", "text": "Malaysia is a highly competitive country and well known for its prowess in various corporate sectors across the globe. As a result, many international investors have a keen interest to gain market penetration and invest in Malaysia to expand to their business empires.", "title": "" }, { "docid": "566076", "text": "For anyone looking to move to a better webhost, you will find many, many webhosting companies that are offering better deals, better service, and more up to date servers than GoDaddy. I can recommend a couple of companies for hosting. For your basic, economy hosting on solid hardware - http://www.serenity-networks.com/ is quite awesome. If you're hosting a site that demands serious performance and is PHP based, http://www.simplehelix.com/ SimpleHelix specializes in high performance PHP and e-commerce sites. Both will walk you through transferring a domain from GoDaddy. Both will migrate your site for free. Both are backed by 24/7 tech support. Happy trails.", "title": "" }, { "docid": "81163", "text": "Obviously it must have been an esthetics thing because they didn't sell, did they? And for any real change to occur is massive adoption of new modfes of transportation and massive capital outlays by Government. Anyone who thinks the private sector is capable of making this change on it's own is delusional. BTW - here are some new technologies that will be hitting the market in coming decade: http://www.popularmechanics.com/cars/news/fuel-economy/6-prototype-engines-to-get-your-brain-firing#fbIndex1 http://www.bbc.co.uk/news/technology-15735478 http://www.smartplanet.com/blog/science-scope/top-10-solar-power-advances-to-watch/1509 http://www.timesunion.com/business/article/Solar-power-advances-bringing-down-cost-1398100.php", "title": "" }, { "docid": "348901", "text": "\"Can confirm - when I owned my business I would outsource some of the \"\"lesser\"\" work to a guy in the Philippines - he was more than $15/hr. This was about 5 years ago, I don't remember exact rate, but I think was about $25/hr. And it was worth it. I had a guy in the US too, who was great and worth every penny, but I couldn't afford him for everything so I used the guy in Philippines for the smaller stuff. I would feel terrible and insulting asking my guy here to work for less. He was worth what he was asking.\"", "title": "" }, { "docid": "306198", "text": "Basically, Our organization arranges the marriage and all of the wedding ceremony features together with wedding videos, wedding cinematography, and wedding videography offerings in Malaysia. Our business enterprise gives the pleasant images, we consider ourselves storytellers, and that’s the identical method we have for Malaysia Wedding cinematic videography. We flow far from the concept that videography has been only a chronological series of wedding occasions", "title": "" }, { "docid": "170372", "text": "Now we will present some a site that offer casino games live mobile, so you can play blackjack and roulette live from your tablet or Smartphone, wherever you are. For all residents, we recommend the GD2 ONE for participating in malaysia cockfight, malaysia gambling website. There you will find everything from banking options to the most popular games, customer service and much more from the best casino sites.", "title": "" }, { "docid": "236581", "text": "\">If mounting debt is such an issue, why do all the markets act as though the US is perfectly solvent? They don't. China, Russia and most emerging markets are selling U.S. treasuries faster and faster. They have started doing so a couple years ago and are doing so at a higher pace now. They sold record numbers of U.S. treasuries in June. Many countries are forging trade partnerships with each other to get away from U.S. debt and even the U.N. and IMF are calling for an end to the dollar as the global reserve currency because it no longer deserves that status, largely due to increasing debt. By the way, the Fed is owning a larger and larger portion of U.S. debt these days. >Why is our interest rate so low, and why do investors around the world continue buying Treasury bonds? The federal reserve keeps rates low. Investors speculate about the future of the market all the time, but they are starting to dump them now http://www.bloomberg.com/news/2014-08-15/u-s-investment-outflow-reaches-record-as-china-sells-treasuries.html http://www.reuters.com/article/2014/08/15/usa-economy-capital-idUSL2N0QL0T520140815 http://www.ft.com/intl/cms/s/0/eaccbe18-aea6-11e3-aaa6-00144feab7de.html >The total net outflow of long-term U.S. securities and short-term funds such as bank transfers was $153.5 billion, after an inflow of $33.1 billion the previous month, the Treasury Department said in a report today. The June figure, and $40.8 billion in net selling of Treasury bonds and notes by private investors in June, were the largest on record, the Treasury said. >\"\"This is a disappointment and is a negative for the dollar. Clearly, the United States is having a hard time attracting investments to offset its current account deficit,\"\" said Michael Woolfolk, global market strategist at BNY Mellon in New York. >Central banks sold US Treasury debt at the start of the year, according to the latest official data released on Tuesday, as stress among emerging market countries intensified. Declines in Treasury holdings were seen for Thailand, Turkey and the Philippines, which sold $3.9bn, $3.3bn and $1.5bn respectively during January. Wow look at that. Did you just dismiss all evidence that proves you wrong? I think so!\"", "title": "" }, { "docid": "272755", "text": "I am also from Malaysia and I just purchase a property around Klang Valley area. Property market is just like share market. You will never know when is the highest peak point and when is the lowest peak point. Yes. Not only you, but everyone of us. What I would say that, just buy according to your need and your financial status. If you feel that you need a comfortable place to stay rather than renting a room, and buying that property will not burden your financial status too much, why not go for it? The best time to purchase property is perhaps last year when world economic is down turn. But thing is over and can never go back. Since all of us don't have a crystal ball to tell the future, why not just act according to your heart and common sense (Buy according to need) ;)", "title": "" }, { "docid": "358018", "text": "Now players from Malaysia can enjoy all online betting games through the best clubs that offer them privacy and safety in all, as well as the best variety of games, rewards and prizes offered by world-class casino clubs, all of which are in accordance with international law governing malaysia online betting games. Best offers in a way that makes them get the most benefit at all, especially after these games are the most acceptable among all the tools of entertainment, either on the personal computer or mobile phone.", "title": "" }, { "docid": "219110", "text": "I never said they're not going to change. I'm saying it will take far more than a year or two. The article say that a $10/barrel can happen in 2 years. I'm saying no. And it's not inefficiency that's causing expensive electricity. Philippines does not have the basic requirements to create cheap and renewable energy to supply what it needs. Nowhere to build a dam for hydro power. And too many strong typhoons/earthquakes for building wind. Solar power would not necessarily work either. The nation is one of the most biodiverse areas in the world. By blocking large chunks of the islands and depriving the land of sunlight, you are causing massive environmental destruction. Palm and agriculture has already devastated many parts of Philippines, what it needs is more vegetation. Tidal power isn't nearly as developed as the other forms of new energy. And it may also disrupt a very busy marine trade route.", "title": "" }, { "docid": "118184", "text": "So why are people still buying 15 year old Saturns or driving the same GM Denali for the last 13 years when the new cars are so much more efficient and cheaper to run? Poor people are fucking poor. Now you turn to Indonesia. How much do you think they are spending to maintain their vehicles? Next to nothing, that's what. They'll only fix it enough to get it running again. SAE certified mechanic? LOL, the guy between the whore house and the cigarette vendor can also do it. How much do you think electricity costs in the Philippines? It can cost $100 USD a month to run the AC at night to get a decent sleep...The average Filipino makes less than $10 a month.", "title": "" }, { "docid": "363197", "text": "malaysia sports betting We strive day and night to make everything work perfectly making sure that you can have fun without worrying about anything. The firm commitment to our users and a determined commitment to safe malaysia sports betting play have led us to implement all the measures and actions that are within our reach to achieve a fair, honest, complete, reliable and totally transparent gaming experience. We take our responsibilities very seriously and focus on what playing is always a fully satisfying experience. Therefore, we also actively work in the promotion of responsible play so that playing never ceases to be a leisure activity full of fun, we watch that strictly comply with the prohibition of access to minors and we turn to answer all your questions And needs.", "title": "" }, { "docid": "347064", "text": "\"Nope, you don't get what I mean. If you put a statement that is not only incorrect, but shows bias, you will get laughed at by anyone. Export means that you take something and then sell them to someone else. That's a positive, and actually exists (though still not quite the correct terminology, it is more apt). For example, the Philippines exports maids to the Middle East. That helps the Filipino economy, unlike what you are saying. But the other thing is that by saying \"\"export\"\", you are already assuming a net loss of jobs, which would not only goes against 90% of economists beliefs, and is the equivalent of starting an abortion debate with, \"\"why do you kill unborn babies\"\", and when anyone corrects you, you claim pedantry. You already showed your bias and pretty much invited a circle jerk by using those words. Which may be fine reddit, where the hive mind laps this up, but ask anyone who's gone beyond studying Macroeconomics, and you won't be taken seriously. The choice is yours, do you want a circle jerk, or do you want to engage in an actual conversation?\"", "title": "" }, { "docid": "10247", "text": "\"Going through the list of economies that currently use the dollar, all of them list cents as a fractional unit. In Hong Kong and Taiwan, the 1/100 fractional unit is still called a cent, but it's no longer in circulation in coin form and only finds use in financial markets or electronic payments. In countries like Malaysia, the word \"\"sen\"\" is used as the translation of the word \"\"cent\"\", even though the word for the actual currency, \"\"ringgit\"\", isn't a translation of the word \"\"dollar\"\". A similar situation occurs in Panama. The local currency is called the balboa, and it's priced on par (1:1) with the US dollar. US banknotes are also accepted as legal tender, and Panamanians sometimes use the terms balboa/dollar interchangeably. The 1/100 subdivision of the balboa is the centésimo, which is merely a translation of cent. Like Malaysia, the fractional unit is called \"\"cent\"\" (or a translation) but the main unit isn't merely a translation of the word \"\"dollar.\"\" On a historical note, the Spanish Dollar was subdivided into 8 reales in order to match the German thaler (the word that forms the basis for the English word \"\"dollar\"\").\"", "title": "" }, { "docid": "368053", "text": "FYI...during the housing boom here in the US many people spoke about ever increasing home prices. Many thought home prices could never go down. Until they did. If it seems like it is impossible for home prices to continue to go up then they probably will stop going up at some point, although the rising prices can continue for a lot longer than you think possible. I'm wondering if Malaysia is feeling the effects of the US FED which flooded the market with US dollars after the crisis. The Malaysian central bank holds US dollars as its foreign exchange reserves. In order to keep the ringgit from rising against the dollar the Malaysian central bank will print up ringgit to purchase dollars which suppresses the value of the ringgit. This has the effect of artificially lowering interest rates as ringgits become readily available leading to a boom - the boom being in real estate. Just a hunch. Is the dinar in Kelantan getting much attention in Malaysia? This is starting to make a little news here.", "title": "" }, { "docid": "50759", "text": "\"1. [National Suicide Prevention Lifeline, http://www.suicidepreventionlifeline.org](http://www.suicidepreventionlifeline.org \"\"National Suicide Prevention Lifeline, 1-800-273-8255\"\") Call toll-free in the United States: 1-800-273-8255 Chat: [http://www.suicidepreventionlifeline.org/GetHelp/LifelineChat.aspx](http://www.suicidepreventionlifeline.org/GetHelp/LifelineChat.aspx) 2. \"\"[For long-unemployed, hiring bias rears its head](http://www.seattlepi.com/news/article/For-long-unemployed-hiring-bias-rears-its-head-3428844.php)\"\" by Stephen Singer, published on 23 March 2012: http://www.seattlepi.com/news/article/For-long-unemployed-hiring-bias-rears-its-head-3428844.php 3. \"\"[The Anxiety of Unemployment](http://opinionator.blogs.nytimes.com/2012/05/21/control/)\"\" by Dominick Brocato and DW Gibson, published on 21 May 2012: http://opinionator.blogs.nytimes.com/2012/05/21/control/ 4. \"\"[Long-term unemployment crisis rolls on](http://money.cnn.com/2012/06/11/news/economy/long-term-unemployment/index.htm)\"\" by Charles Riley, published on 11 June 2012: http://money.cnn.com/2012/06/11/news/economy/long-term-unemployment/index.htm 5. \"\"[Philadelphia Woman, 73, Says Age Has Kept Her Unemployed for Two Years](http://abcnews.go.com/Business/73-year-philadelphia-woman-testifies-age-discrimination-job/story?id=16352837&singlePage=true)\"\" by Susanna Kim, published on 16 May 2012: http://abcnews.go.com/Business/73-year-philadelphia-woman-testifies-age-discrimination-job/story?id=16352837&singlePage=true\"", "title": "" }, { "docid": "239734", "text": "Most of the points by MrChrister are valid. I can't say much for Philippines, however there is a reason for one to go with individual insurance from my experience in India.", "title": "" }, { "docid": "511647", "text": "\"This page from TripAdvisor may be of interest. Look at what fees are charged on your ATM cards and credit cards, and consider overpaying your credit card so you have a credit balance that you can draw on for cash \"\"advances\"\" from ATMs that will dispense in local currency. Depending on what fees your bank charges, you may get a better rate than the forex cash traders at the airport. Edit: Cards may not always have the best rate. I recently heard from a traveler who was able to use a locally but not globally dominant currency to buy cash of a major currency at a shopping mall (with competitive forex traders) at rates even better than the mid-market rates posted at xe.com and similar places; I don't think you'll have that experience going from Australia to Malaysia (but another traveler reading this might have a different pair). In my experience the card rates are slightly worse than those and the airport forex traders significantly worse.\"", "title": "" } ]
6966	Perform exercise-and-hold AND exercise-and-sell-to-cover?	[ { "docid": "435463", "text": "Ask the folks administering your plan. They're the ones who define and implement the available choices for that specific plan.", "title": "" }, { "docid": "15635", "text": "\"The simplest thing to do here is to speak to your employer about what is allowed. This should be spelt out in your company's \"\"Stock Options Plan\"\" documentation. In particular, this document will include details of the vesting schedule. For example, the schedule may only allow you to exercise 25% in the first year, 25% in the second year, and the remainder in the third year. Technically I can see no reason to prevent you from the mix-and-match approach you are suggesting. However, this may not be the case according to the schedule specification.\"", "title": "" } ]	[ { "docid": "119976", "text": "\"One alternative strategy you may want to consider is writing covered calls on the stock you have \"\"just sitting there\"\". This will allow you to earn a return (the premium from the calls) without necessarily having to give up your holding. As a brief overview, \"\"options\"\" are derivatives that give the holder the right (or option) to buy or sell shares at a specified price. Holders of call options with a strike prike $x on a particular security have the right to purchase that security at the strike price $x. Conversely, holders of put options with a strike price of $x have the right to sell that security at the strike price $x. Always on the other side of a call or put option is a person that has sold the option, which is called \"\"writing\"\" the option. If this person writes a call option, then he will be obligated to sell a certain amount of stock (100 shares per contract) at the strike price if that option is exercised. A writer of a put option will be obligated to by 100 shares per contract at the strike price if that option is exercised. Covered calls involve writing call contracts on stock that you own. For example, say you own 100 shares of AAPL, and that AAPL is currently trading for $330. You decide to write a Jan 21, 2012 call on these shares at a strike price of $340, earning you a premium of say $300. Two things can now happen: if the price of AAPL is not at least $340 on January 21, then the options are \"\"out of the money\"\" and will expire unexercised (why exercise an option to buy at $340 when you can buy at the currently cheaper market price?). You keep your AAPL stock plus the $300 premium you earn. If, however, the price of AAPL is greater than $340, the option will be exercised and you will now be required to sell the shares you own at $340. You will earn a return of $10/share ($340-$330), plus the $300 premium from the call option. You still make out in the end, but have unfortunately incurred an opportunity cost, as had you not written the call option you would have been able to sell at the market price, which is higher than the $340 strike price. Covered calls are considered relatively safe and conservative, however the strategy is most effective for stocks that are expected to stay within a relatively narrow price range for the duration of the contract. They do provide one option of earning additional money on stocks you are currently holding, albeit at the risk of giving up some returns if the stock price rises above the strike price.\"", "title": "" }, { "docid": "578022", "text": "\"You owe no tax on the option transaction in 2015 in this case. How you ultimately get taxed depends on how you dispose of the position. If it expires, then you will have a short-term capital gain on the option position at expiration. If it is exercised, then the option is \"\"gone\"\" for tax purposes and your basis in the underlying is adjusted. From IRS Publication 550: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. In your case, this will be a long-term capital gain. For completeness, if you buy to cover the option back from the market before expiration or exercise, then it is also a short-term capital gain. Also, keep in mind that this all assumes that this covered call is \"\"qualified\"\" so that it does not count as a straddle. You can find more about that in Pub 550. https://www.irs.gov/publications/p550/ch04.html#en_US_2014_publink100010630 All of this is for US tax purposes.\"", "title": "" }, { "docid": "118360", "text": "First, it depends on your broker. Full service firms will tear you a new one, discount brokers may charge ~nothing. You'll have to check with your broker on assignment fees. Theoretically, this is the case of the opposite of my answer in this question: Are underlying assets supposed to be sold/bought immediately after being bought/sold in call/put option? Your trading strategy/reasoning for your covered call notwithstanding, in your case, as an option writer covering in the money calls, you want to hold and pray that your option expires worthless. As I said in the other answer, there is always a theoretical premium of option price + exercise price to underlying prices, no matter how slight, right up until expiration, so on that basis, it doesn't pay to close out the option. However, there's a reality that I didn't mention in the other answer: if it's a deep in the money option, you can actually put a bid < stock price - exercise price - trade fee and hope for the best since the market makers rarely bid above stock price - exercise price for illiquid options, but it's unlikely that you'll beat the market makers + hft. They're systems are too fast. I know the philly exchange allows you to put in implied volatility orders, but they're expensive, and I couldn't tell you if a broker/exchange allows for dynamic orders with the equation I specified above, but it may be worth a shot to check out; however, it's unlikely that such a low order would ever be filled since you'll at best be lined up with the market makers, and it would require a big player dumping all its' holdings at once to get to your order. If you're doing a traditional, true-blue covered call, there's absolutely nothing wrong being assigned except for the tax implications. When your counterparty calls away your underlyings, it is a sell for tax purposes. If you're not covering with the underlying but with a more complex spread, things could get hairy for you real quick if someone were to exercise on you, but that's always a risk. If your broker is extremely strict, they may close the rest of your spread for you at the offer. In illiquid markets, that would be a huge percentage loss considering the wide bid/ask spreads.", "title": "" }, { "docid": "444668", "text": "\"You seem to have a little confusion over terminology that should be cleared up: You are calling this \"\"day-trading\"\" Day-trading is the term for performing multiple trading actions in a single day. While it appears that the COO has performed a buy and a sell on the same day, most people would consider this a 'single trade'. In reality, it seems that the COO had 'stock options' [a contract providing the option for the holder to buy stock at a specific price, at some point in the future], provided as part of his compensation package. He decided or was required to 'exercise' those options today. This means he bought the shares using his special 'option price'. It is extremely common for employees who exercise stock options, to sell all of the resulting stock immediately. This is very different from usual day-trading, which implies that he would have bought stock in the morning at a low price, and then sold it later at a high price. You are calling this 'insider trading'. That term specifically often implies some level of unethical behavior. In general, stock options offered to executive employees are strictly limited in how they can be exercised. For example, most stock option plans require employees to wait x number of years before they can exercise them. This gives the employee incentive to stay longer, and for a high-level executive with the ability to strongly impact company performance, it gives incentive to do well. Technically you are correct, this is likely considered an 'insider trade', but given that it seems to have been a stock option exercise, it does not necessarily imply that there was any special reasoning for why he did the trade today. It could simply be that today was the first day the stock option rules allowed him to exercise. As to your final question - no, these profits are the COO's, to do with as he likes.\"", "title": "" }, { "docid": "336541", "text": "\"There is unlimited risk in taking a naked call option position. The only risk in taking a covered call position is that you will be required to sell your shares for less than the going market price. I don't entirely agree with the accepted answer given here. You would not lose the amount you paid to buy the shares. Naked Call Option Suppose take a naked call option position by selling a call option. Since there is no limit on how high the price of the underlying share can go, you can be forced to either buy back the option at a very high price, or, in the case that the option is exercised, you can be force. to buy the underlying shares at a very high price and then sell them to the option holder at a very low price. For example, suppose you sell an Apple call option with a strike price of $100 at a premium of $2.50, and for this you receive a payment of $250. Now, if the price of Apple skyrockets to, say, $1000, then you would either have to buy back the option for about $90,000 = 100 x ($1000-$100), or, if the holder exercised the option, then you would need to buy 100 Apple shares at the market price of $1000 per share, costing you $100,000, and then sell them to the option holder at the strike price of $100 for $10,000 = 100 x $100. In either case, you would show a loss of $90,000 on the share transaction, which would be slightly offset by a $250 credit for the premium you received selling the call. There is no limit on the potential loss since there is no limit on how high the underlying share price can go. Covered Call Option Consider now the case of a covered call option. Since you hold the underlying shares, any loss you make on the option position would be \"\"covered\"\" by the profit you make on the underlying shares. Again, suppose you own 100 Apple shares and sell a call option with a strike price of $100 at a premium of $2.50 to earn a payment of $250. If the price of Apple skyrockets to $1000, then there are again two possible scenarios. One, you buy back the option at a premium of about $900 costing you $90,000. In order to cover this cost you would then sell your 100 Apple shares at the market price of $1000 per share to realise $100,000 = 100 x $1000. On the other hand, if your option is exercised, then you would deliver your 100 Apple shares to the option holder at the contracted strike price of $100 per share, thus receiving just $10,000 = 100 x $100. The only \"\"loss\"\" is that you have had to sell your shares for much less than the market price.\"", "title": "" }, { "docid": "226546", "text": "\"Your broker likely didn't close your position out because it is a covered position. Why interfere with a trade that has no risk to it, from their perspective? There's no risk for the broker since your account holds the shares available for delivery (definition of covered), for if and when the options you wrote (sold) are exercised. And buyers of those options will eventually exercise the options (by expiration) if they remain in-the-money. There's only a chance that an option buyer exercises prematurely, and usually they don't because there's often time value left in the option. That the option buyer has an (ahem) \"\"option\"\" to exercise is a very key point. You wrote: \"\"I fully expected my position to be automatically liquidated by whoever bought my call\"\". That's a false assumption about the way options actually work. I suggest some study of the option exercise FAQs here: Perhaps if your position were uncovered – i.e. you wrote the call without owning the stock (don't try this at home, kids!) – and you also had insufficient margin to cover such a short position, then the broker might have justifiably liquidated your position. Whereas, in a covered call situation, there's really no reason for them to want to interfere – and I would consider that interference, as opposed to helpful. The situation you've described is neither risky for them, nor out of the ordinary. It is (and should be) completely up to you to decide how to close out the position. Anyway, your choices generally are:\"", "title": "" }, { "docid": "380951", "text": "You are asking 'what if', do you have some anticipated answers? Having volume smaller than open interest is the norm. As far as I can tell, having only one trading day and no previous open interest only affects someone trying to sell a contract they are holding. Meaning that if you only have one day to sell your contract then you need to offer it 'at market' or at the bid price (or even lower than the bid price). If you cannot sell your contract then you have to let it expire worthless or you have to exercise it. Those are your three options: let it expire, sell it (perhaps at a loss), and exercise it. Edit: be careful about holding an in-the-money option. Many brokers will automatically exercise an in-the-money contract if you hold it till expiration date.", "title": "" }, { "docid": "507828", "text": "\"I'm adding to @Dilip's basic answer, to cover the additional points in your question. I'll assume you are referring to publicly traded stock options, such as those found on the CBOE, and not an option contract entered into privately between two specific counterparties (e.g. as in an employer stock option plan). Since you are not obligated to exercise a call option you purchased on the market, you don't need to maintain funds on account for possible exercising. You could instead let the option expire, or resell the option, neither of which requires funds available for purchase of the underlying shares. However, should you actually choose to exercise the call option (and usually this is done close to expiration, if at all), you will be required to fund your account much like if you bought the underlying shares in the first place. Call your broker to determine the exact rules and timing for when they need the money for a call-option exercise. And to expand on the idea of \"\"cancelling\"\" an option you purchased: No, you cannot \"\"cancel\"\" an option contract, per se. But, you are permitted to sell the call option to somebody else willing to buy, via the market. When you sell your call option, you'll either make or lose money on the sale – depending on the price of the underlying shares at the time (are they in- or out- of the money?), volatility in the market, and remaining time value. Once you sell, you're back to \"\"no position\"\". That's not the same as \"\"cancelled\"\", but you are out of the trade, whether at profit or loss. Furthermore, the option writer (i.e. the seller who \"\"sold to open\"\" a position, in writing the call in the first place) is also not permitted to cancel the option he wrote. However, the option writer is permitted to close out the original short position by simply buying back a matching call option on the market. Again, this would occur at either profit or loss based on market prices at the time. This second kind of buy order – i.e. made by someone who initially wrote a call option – is called a \"\"buy to close\"\", meaning the purchase of an offsetting position. (The other kind of buy is the \"\"buy to open\"\".) Then, consider: Since an option buyer is free to re-sell the option purchased, and since an option writer (who \"\"sold to open\"\" the new contract) is also free to buy back an offsetting option, a process known as clearing is required to match remaining buyers exercising the call options held with the remaining option writers having open short positions for the contract. For CBOE options, this clearing is performed by the Options Clearing Corporation. Here's how it works (see here): What is the OCC? The Options Clearing Corporation is the sole issuer of all securities options listed at the CBOE, four other U.S. stock exchanges and the National Association of Securities Dealers, Inc. (NASD), and is the entity through which all CBOE option transactions are ultimately cleared. As the issuer of all options, OCC essentially takes the opposite side of every option traded. Because OCC basically becomes the buyer for every seller and the seller for every buyer, it allows options traders to buy and sell in a secondary market without having to find the original opposite party. [...] [emphasis above is mine] When a call option writer must deliver shares to a call option buyer exercising a call, it's called assignment. (I have been assigned before, and it isn't pleasant to see a position called away that otherwise would have been very profitable if the call weren't written in the first place!) Also, re: \"\"I know my counter party cannot sell his shares\"\" ... that's not strictly true. You are thinking of a covered call. But, an option writer doesn't necessarily need to own the underlying shares. Look up Naked call (Wikipedia). Naked calls aren't frequently undertaken because a naked call \"\"is one of the riskiest options strategies because it carries unlimited risk\"\". The average individual trader isn't usually permitted by their broker to enter such an order, but there are market participants who can do such a trade. Finally, you can learn more about options at The Options Industry Council (OIC).\"", "title": "" }, { "docid": "193717", "text": "\"You mention \"\"early exercise\"\" in your title, but you seem to misunderstand what early exercise really means. Some companies offer stock options that vest over a number of years, but which can be exercised before they are vested. That is early exercise. You have vested stock options, so early exercise is not relevant. (It may or may not be the case that your stock options could have been early exercised before they vested, but regardless, you didn't exercise them, so the point is moot.) As littleadv said, 83(b) election is for restricted stocks, often from exercising unvested stock options. Your options are already vested, so they won't be restricted stock. So 83(b) election is not relevant for you. A taxable event happen when you exercise. The point of the 83(b) election is that exercising unvested stock options is not a taxable event, so 83(b) election allows you to force it to be a taxable event. But for you, with vested stock options, there is no need to do this. You mention that you want it not to be taxable upon exercise. But that's what Incentive Stock Options (ISOs) are for. ISOs were designed for the purpose of not being taxable for regular income tax purposes when you exercise (although it is still taxable upon exercise for AMT purposes), and it is only taxed when you sell. However, you have Non-qualified Stock Options. Were you given the option to get ISOs at the beginning? Why did your company give you NQSOs? I don't know the specifics of your situation, but since you mentioned \"\"early exercise\"\" and 83(b) elections, I have a hypothesis as to what might have happened. For people who early-exercise (for plans that allow early-exercise), there is a slight advantage to having NQSOs compared to ISOs. This is because if you early exercise immediately upon grant and do 83(b) election, you pay no taxes upon exercise (because the difference between strike price and FMV is 0), and there are no taxes upon vesting (for regular or AMT), and if you hold it for at least 1 year, upon sale it will be long-term capital gains. On the other hand, for ISOs, it's the same except that for long-term capital gains, you have to hold it 2 years after grant and 1 year after exercise, so the period for long-term capital gains is longer. So companies that allow early exercise will often offer employees either NQSOs or ISOs, where you would choose NQSO if you intend to early-exercise, or ISO otherwise. If (hypothetically) that's what happened, then you chose wrong because you got NQSOs and didn't early exercise.\"", "title": "" }, { "docid": "345410", "text": "The crucial insight is that the alternative to early exercise of an American call is not necessarily to hold it to expiry, but to sell it. And selling it, at its value, is always better than exercising it. Note that this holds only for options on assets that don't pay dividends. Here's the proof, using Put-Call-Parity. We know that at expiry T, we have (using a Call and a Put both struck at K): C(T) - P(T) = S(T) - K (if this is not clear to you, consider the case where S is less than, equal to, or greater than K at maturity, and go through each of them.) If the stock S doesn't pay any dividends (and there is no cost of carry etc.), we can replicate both sides now at time 0; we just buy one call, sell one put (that gives us the left hand side), buy the stock, and borrow money so that at time T we have to repay K (that gives us the right hand side). That means that now, we only need to borrow df * K, where df is the discount factor, and is less than one (assuming the good old pre-2009 world where interest rates are positive). Thus: C(0) - P(0) = S(0) - df * K. Rearranging gives: C(0) = S(0) - df * K + P(0). That's the value of the call, if we sell it (or hold it). However, if we exercise, we only get: C_ex = S(0) - K Now, we see that C(0) > C_ex, because we subtract less (dfK < K), and add P(0).", "title": "" }, { "docid": "528052", "text": "\"Your question indicates that you might have a little confusion about put options and/or leveraging. There's no sense I'm aware of in which purchasing a put levers a position. Purchasing a put will cost you money up front. Leveraging typically means entering a transaction that gives you extra money now that you can use to buy other things. If you meant to sell a put, that will make money up front but there is no possibility of making money later. Best case scenario the put is not exercised. The other use of the term \"\"leverage\"\" refers to purchasing an asset that, proportionally, goes up faster than the value of the underlying. For example, a call option. If you purchase a put, you are buying downside protection, which is kind of the opposite of leverage. Notice that for an American put you will most likely be better off selling the put when the price of the underlying falls than exercising it. That way you make the money you would have made by exercising plus whatever optional value the put still contains. That is true unless the time value of money is greater than the optional (insurance) value. Since the time value of money is currently exceptionally low, this is unlikely. Anyway, if you sell the option instead of exercising, you don't need to own any shares at all. Even if you do exercise, you can just buy them on the market and sell right away so I wouldn't worry about what you happen to be holding. The rules for what you can trade with a cash instead of a margin account vary by broker, I think. You can usually buy puts and calls in a cash account, but more advanced strategies, such as writing options, are prohibited. Ask your broker or check their help pages to see what you have available to you.\"", "title": "" }, { "docid": "220147", "text": "Options granted by an employer to an employee are generally different that the standardized options that are traded on public stock option exchanges. They may or may not have somewhat comparable terms, but generally the terms are fairly different. As a holder of an expiring employee option, you can only choose to exercise it by paying the specified price and receiving the shares, or not. It is common that the exercise system will allow you to exercise all the shares and simultaneously sell enough of the acquired shares to cover the option cost of all the shares, thus leaving you owning some of the stock without having to spend any cash. You will owe taxes on the gain on exercise, regardless of what you do with the stock. If you want to buy publicly-traded options, you should consider that completely separately from your employer options other than thinking about how much exposure you have to your company situation. It is very common for employees to be imprudently overexposed to their company's stock (through direct ownership or options).", "title": "" }, { "docid": "242298", "text": "\"4PM is the market close in NYC, so yes, time looks good. If \"\"out of the money,\"\" they expire worthless. If \"\"in the money,\"\" it depends on your broker's rules, they can exercise the option, and you'll need to have the money to cover on Monday or they can do an exercise/sell, in which case, you'd have two commissions but get your profit. The broker will need to tell you their exact procedure, I don't believe it's universal.\"", "title": "" }, { "docid": "89484", "text": "You could have both options exercised (and assigned to you) on the same day, but I don't think you could lose money on both on the same day. The reason is that while exercises are immediate, assignments are processed after the markets close at the end of each day. See http://www.888options.com/help/faq/assignment.jsp for details. So you would get both assignments at the same time, that night. The net effect should be that you don't own any stock (someone would put you the stock, then it'd be called away) and you don't have the options anymore. You should have incoming cash of $1500 selling the stock to the call exerciser and outgoing cash of $1300 buying from the put exerciser, right? So you would have no more options but $200 more cash in your account in the morning. You bought at 13 and sold at 15. This options position is an agreement to buy at 13 and sell at 15 at someone else's option. The way you lose money is if one of the options isn't exercised while the other is, i.e. if the stock is below 13 so nobody is going to opt to buy from you at 15, but they'll sell to you at 13; or above 15 so nobody is going to opt to sell to you at 13, but they'll buy from you at 15. You make money if neither is exercised (you keep the premium you sold for) or both are exercised (you keep the gap between the two, plus the premium). Having both exercised is surely rare, since early exercise is rare to begin with, and tends to happen when options are deep in the money; so you'd expect both to be exercised if both are deep in the money at some point. Having both be exercised on the same day ... can't be common, but it's maybe most likely just before expiration with minimal time value, if the stock moves around quickly so both options are in the money at some point during the day.", "title": "" }, { "docid": "388754", "text": "\"The question you are asking concerns the exercise of a short option position. The other replies do not appear to address this situation. Suppose that Apple is trading at $96 and you sell a put option with a strike price of $95 for some future delivery date - say August 2016. The option contract is for 100 shares and you sell the contract for a premium of $3.20. When you sell the option your account will be credited with the premium and debited with the broker commission. The premium you receive will be $320 = 100 x $3.20. The commission you pay will depend on you broker. Now suppose that the price of Apple drops to $90 and your option is exercised, either on expiry or prior to expiry. Then you would be obliged to take delivery of 100 Apple shares at the contracted option strike price of $95 costing you $9,500 plus broker commission. If you immediately sell the Apple shares you have purchased under your contract obligations, then assuming you sell the shares at the current market price of $90 you would realise a loss of $500 ( = 100x($95-$90) )plus commission. Since you received a premium of $320 when you sold the put option, your net loss would be $500-$320 = $180 plus any commissions paid to your broker. Now let's look at the case of selling a call option. Again assume that the price of Apple is $96 and you sell a call option for 100 shares with a strike price of $97 for a premium of $3.60. The premium you receive would be $360 = 100 x $3.60. You would also be debited for commission by your broker. Now suppose that the price of Apple shares rises to $101 and your option is exercised. Then you would be obliged to deliver 100 Apple shares to the party exercising the option at the contracted strike price of $97. If you did not own the shares to effect delivery, then you would need to purchase those shares in the market at the current market price of $101, and then sell them to the party exercising the option at the strike price of $97. This would realise an immediate loss of $400 = 100 x ($101-$97) plus any commission payable. If you did own the shares, then you would simply deliver them and possibly pay some commission or a delivery fee to your broker. Since you received $360 when you sold the option, your net loss would be $40 = $400-$360 plus any commission and fees payable to the broker. It is important to understand that in addition to these accounting items, short option positions carry with them a \"\"margin\"\" requirement. You will need to maintain a margin deposit to show \"\"good faith\"\" so long as the short option position is open. If the option you have sold moves against you, then you will be called upon to put up extra margin to cover any potential losses.\"", "title": "" }, { "docid": "382381", "text": "\"You are thinking about it this way: \"\"The longer I wait to exericse, the more knowledge and information I'll have, thus the more confidence I can have that I'll be able to sell at a profit, minimizing risk. If I exercise early and still have to wait, there may never be a chance I can sell at a profit, and I'll have lost the money I paid to exercise and any tax I had to pay when I exercised.\"\" All of that is true. But if you exercise early: The fair market value of the stock will probably be lower, so you may pay less income tax when you exercise. (This depends on your tax situation. Currently, ISO exercises affect your AMT.) If the company goes through a phase where the value is unusually high, you'll be able to sell and still get the tax benefits because you exercised earlier. You avoid the nightmare scenario where you leave the company (voluntarily or not) and can't afford to exercise your options because of the tax implications. In many realistic cases, exercising earlier means less risk. Imagine if you're working at a company that is privately held and you expect to be there for another year or so. You are very optimistic about the company, but not sure when it will IPO or get acquired and that may be several years off. The fair market value of the stock is low now, but may be much higher in a year. In this case, it makes a lot of sense to exercise now. The cost is low because the fair market value is low so it won't result in a huge tax bill. And then when you leave in a year, you won't have to choose between forfeiting your options or borrowing money to pay the much higher taxes due to exercise them then.\"", "title": "" }, { "docid": "305676", "text": "\"In general there are two types of futures contract, a put and call. Both contract types have both common sides of a transaction, a buyer and a seller. You can sell a put contract, or sell a call contract also; you're just taking the other side of the agreement. If you're selling it would commonly be called a \"\"sell to open\"\" meaning you're opening your position by selling a contract which is different from simply selling an option that you currently own to close your position. A put contract gives the buyer the right to sell shares (or some asset/commodity) for a specified price on a specified date; the buyer of the contract gets to put the shares on someone else. A call contract gives the buyer the right to buy shares (or some asset/commodity) for a specified price on a specified date; the buyer of the contract gets to call on someone for shares. \"\"American\"\" options contracts allow the buyer can exercise their rights under the contract on or before the expiration date; while \"\"European\"\" type contracts can only be exercised on the expiration date. To address your example. Typically for stock an option contract involves 100 shares of a stock. The value of these contracts fluctuates the same way other assets do. Typically retail investors don't actually exercise their contracts, they just close a profitable position before the exercise deadline, and let unprofitable positions expire worthless. If you were to buy a single call contract with an exercise price of $100 with a maturity date of August 1 for $1 per share, the contract will have cost you $100. Let's say on August 1 the underlying shares are now available for $110 per share. You have two options: Option 1: On August 1, you can exercise your contract to buy 100 shares for $100 per share. You would exercise for $10,000 ($100 times 100 shares), then sell the shares for $10 profit per share; less the cost of the contract and transaction costs. Option 2: Your contract is now worth something closer to $10 per share, up from $1 per share when you bought it. You can just sell your contract without ever exercising it to someone with an account large enough to exercise and/or an actual desire to receive the asset or commodity.\"", "title": "" }, { "docid": "171819", "text": "\"There some specific circumstances when you would have a long-term gain. Option 1: If you meet all of these conditions: Then you've got a long-term gain on the stock. The premium on the option gets rolled into the capital gain on the stock and is not taxed separately. From the IRS: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010630 Option 2: If you didn't hold the underlying and the exercise of the call that you wrote resulted in a short position, you might also be able to get to a long-term gain by buying the underlying while keeping your short position open and then \"\"crossing\"\" them to close both positions after one year. (In other words, don't \"\"buy to cover\"\" just \"\"buy\"\" so that your account shows both a long and a short position in the same security. Your broker probably allows this, but if not you, could buy in a different account than the one with the short position.) That would get you to this rule: As a general rule, you determine whether you have short-term or long-term capital gain or loss on a short sale by the amount of time you actually hold the property eventually delivered to the lender to close the short sale. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010586 Option 1 is probably reasonably common. Option 2, I would guess, is uncommon and likely not worthwhile. I do not think that the wash sale rules can help string along options from expiration to expiration though. Option 1 has some elements of what you wrote in italics (I find that paragraph a bit confusing), but the wash sale does not help you out.\"", "title": "" }, { "docid": "388362", "text": "\"The other two answers seem basically correct, but I wanted to add on thing: While you can exercise an \"\"American style\"\" option at any time, it's almost never smart to do so before expiration. In your example, when the underlying stock reaches $110, you can theoretically make $2/share by exercising your option (buying 100 shares @ $108/share) and immediately selling those 100 shares back to the market at $110/share. This is all before commission. In more detail, you'll have these practical issues: You are going to have to pay commissions, which means you'll need a bigger spread to make this worthwhile. You and those who have already answered have you finger on this part, but I include it for completeness. (Even at expiration, if the difference between the last close price and the strike price is pretty close, some \"\"in-the-money\"\" options will be allowed to expire unexercised when the holders can't cover the closing commission costs.) The market value of the option contract itself should also go up as the price of the underlying stock goes up. Unless it's very close to expiration, the option contract should have some \"\"time value\"\" in its market price, so, if you want to close your position at this point, earlier then expiration, it will probably be better for you to sell the contract back to the market (for more money and only one commission) than to exercise and then close the stock position (for less money and two commissions). If you want to exercise and then flip the stock back as your exit strategy, you need to be aware of the settlement times. You probably are not going to instantly have those 100 shares of stock credited to your account, so you may not be able to sell them right away, which could leave you subject to some risk of the price changing. Alternatively, you could sell the stock short to lock in the price, but you'll have to be sure that your brokerage account is set up to allow that and understand how to do this.\"", "title": "" }, { "docid": "457059", "text": "\"There are different schools of thought. You can ask the IRS - and it would not surprise me if you got different answers on different phone calls. One interpretation is that a put is not \"\"substantially identical\"\" to the disposed stock, therefore no wash is triggered by that sale. However if that put is exercised, then you automatically purchase the security, and that is identical. As to whether the IRS (or your brokerage firm) recognizes the identical security when it falls out of an option, I can't say; but technically they could enforce it because the rule is based on 30 days and a \"\"substantially identical\"\" stock or security. In this interpretation (your investor) would probably at least want to stay out of the money in choosing a strike price, to avoid exercise; however, options are normally either held or sold, rather than be exercised, until at or very close to the expiration date (because time value is left on the table otherwise). So the key driver in this interpretation would be expiration date, which should be at least 31 days out from the stock sale; and it would be prudent to sell an out of the money put as well, in order to avoid the wash sale trigger. However there is also a more unfavorable opinion - see fairmark.com/capgain/wash/wsoption.htm where they hold that a \"\"deep in the money\"\" option is an immediate trigger (regardless of exercise). This article is sage, in that they say that the Treasury (IRS) may interpret an option transaction as a wash if it's ballpark to being exercisable. And, if the IRS throws paper, it always beats each of paper, rock and scissors :( A Schwab article (\"\"A Primer on Wash Sales\"\") says, if the CUSIPs match, bang, wash. This is the one that they may interpret unfavorably on in any case, supporting Schwab's \"\"play it safe\"\" position: \"\"3. Acquire a contract or option to buy substantially identical stock or securities...\"\" . This certainly nails buying a call. As to selling a put, well, it is at least conceivable that an IRS official would call that a contract to buy! SO it's simply not a slam dunk; there are varying opinions that you might describe as ranging from \"\"hell no\"\" to \"\"only if blatant.\"\" If you can get an \"\"official\"\" predetermination, or you like to go aggressive in your tax strategy, there's that; they may act adversely, so Caveat Taxfiler!\"", "title": "" }, { "docid": "7733", "text": "Options that are not worth exercising just expire. Options that are worth exercising are typically exercised automatically as they expire, resulting in a transfer of stock between the entity that issued the option and the entity that holds it. OCC options automatically exercise when they expire if the value of the option exceeds the transaction cost for the stock transfer (1/4 point to 3/4 point depending).", "title": "" }, { "docid": "194605", "text": "There are a few situations in which it may be advantageous to exercise early. Wikipedia actually has a good explanation: Option Style, Difference in value To account for the American's higher value there must be some situations in which it is optimal to exercise the American option before the expiration date. This can arise in several ways, such as: An in the money (ITM) call option on a stock is often exercised just before the stock pays a dividend that would lower its value by more than the option's remaining time value. A put option will usually be exercised early if the underlying asset files for bankruptcy.[3] A deep ITM currency option (FX option) where the strike currency has a lower interest rate than the currency to be received will often be exercised early because the time value sacrificed is less valuable than the expected depreciation of the received currency against the strike. An American bond option on the dirty price of a bond (such as some convertible bonds) may be exercised immediately if ITM and a coupon is due. A put option on gold will be exercised early when deep ITM, because gold tends to hold its value whereas the currency used as the strike is often expected to lose value through inflation if the holder waits until final maturity to exercise the option (they will almost certainly exercise a contract deep ITM, minimizing its time value).[citation needed]", "title": "" }, { "docid": "288289", "text": "As other answers state, selling the options contracts to the market is a definite way out, and probably the best in most cases. If you're determined to exercise your options (or there's not enough liquidity to reasonably sell your contracts to the market), then you could plan ahead and exercise smaller number of contracts at a time and sell the resulting position in the underlying, which will give you funds to exercise some more contracts and sell the underlying. If you think you're going down this path, however, make sure that you take into account your broker's rules for settlement. You may need to start the exercise / sell cycle before the option's expiration date.", "title": "" }, { "docid": "18173", "text": "The Evostfitness launch a new Exercise Equipment shoulder press E-1006 works several muscles of the upper body and offers a host of benefits that improve daily functioning. This exercise can be performed with Shoulder Press E-1006 Strength Gym Equipment, resistance bands or a machine.and Intelligent ergonomic design features comfortable, oversized grips with multiple positions, adjustable seat pad for desired start position.An important benefit of the shoulder press exercise, as well as any other strength-training exercise, is increased bone strength. During the lift, the load placed on your bones by the weights stresses them and causes them to adapt, just like your muscles. For More Information visit on:-www.evostfitness.com For any Queries kindly contact us at:[email protected]", "title": "" }, { "docid": "428399", "text": "An option gives you the option rather than the obligation to buy (or sell) the underlying so you don't have to exercise you can just let the option expire (so long it doesn't have an automatic expiry). After expiration the option is worthless if it is out of the money but other than that has no hangover. Option prices normally drop as the time value of the option decays. An option has two values associated with it; time value and exercise value. Far out of the money (when the price of the underlying is far from the strike price on the losing side) options only have time value whereas deep in the money options (as yours seems to be) has some time value as well as the intrinsic value of the right to buy (sell) at a low (high) price and then sell (buy) the underlying. The time value of the option comes from the possibility that the price of the underlying will move (further) in your favour and make you more money at expiry. As expiry closes it is less likely that there will be a favourable mood so this value declines which can cause prices to move sharply after a period of little to no revaluing. Up to now what I have said applies to both OTC and traded options but exchange traded options have another level of complexity in their trading; because there are fewer traders in the options market the size of trade at which you can move the market is much lower. On the equities markets you may need to trade millions of shares to have be substantial enough to significantly move a price, on the options markets it could be thousands or even hundreds. If these are European style options (which sounds likely) and a single trading entity was holding a large number of the exchange traded options and now thinks that the price will move significantly against them before expiry their sell trade will move the market lower in spite of the options being in the money. Their trade is based on their supposition that by the time they can exercise the option the price will be below the strike and they will lose money. They have cashed out at a price that suited them and limited what they will lose if they are right about the underlying. If I am not correct in my excise style assumption (European) I may need more details on the trade as it seems like you should just exercise now and take the profit if it is that far into the money.", "title": "" }, { "docid": "261258", "text": "I've never heard of an employer offering this kind of arrangement before, so my answer assumes there is no special tax treatment that I'm not aware of. Utilizing the clause is probably equivalent to exercising some of your options, selling the shares back to your employer at FMV, and then exercising more options with the proceeds. In this case if you exercise 7500 shares and sell them back at FMV, your proceeds would be 7500 x $5 = $37,500, with which you could exercise the remaining 12,500 options. The tax implications would be (1) short-term capital gains of 7500 x ($5 - $3) = $15,000 and (2) AMT income of 12,500 x ($5 - $3) = $25,000, assuming you don't sell the shares within the calendar year.", "title": "" }, { "docid": "352700", "text": "It depends how deep in the money it is, compared to the dividend. Even an in the money call has some time premium. As the call holder, if I exercise instead of selling the call, I am trading the potential for a dividend, which I won't receive, for getting that time premium back by selling. Given the above, you'll notice a slight distortion in options pricing as a dividend date approaches, as the option will reflect not just the time premium, but the fact that exercising with grab the dividend. Edit to address your comment - $10 stock, $9 strike, 50 cent div. If the option price is high, say $2, because there's a year till expiration, exercising makes no sense. If it's just $1.10, I gain 40 cents by exercising and selling after the dividend.", "title": "" }, { "docid": "541928", "text": "American options (like those on ADBE) can be exercised by the holder anytime before expiration. They will be exercised automatically at expiration if they are in the money. However, if there is still time before expiration (as in this case), and they are not extremely in the money, there is probably extrinsic value to the option, and you should sell it, not exercise it. European options are only automatically exercised at expiration, and only if they are in the money. These are usually cash settled on products like SPX or VIX. They can not be exercised before expiration, but can be sold anytime.", "title": "" }, { "docid": "254474", "text": "\"I think the question, as worded, has some incorrect assumptions built into it, but let me try to hit the key answers that I think might help: Your broker can't really do anything here. Your broker doesn't own the calls you sold, and can't elect to exercise someone else's calls. Your broker can take action to liquidate positions when you are in margin calls, but the scenario you describe wouldn't generate them: If you are long stock, and short calls, the calls are covered, and have no margin requirement. The stock is the only collateral you need, and you can have the position on in a cash (non-margin) account. So, assuming you haven't bought other things on margin that have gone south and are generating calls, your broker has no right to do anything to you. If you're wondering about the \"\"other guy\"\", meaning the person who is long the calls that you are short, they are the one who can impact you, by exercising their right to buy the stock from you. In that scenario, you make $21, your maximum possible return (since you bought the stock at $100, collected $1 premium, and sold it for $120. But they usually won't do that before expiration, and they pretty definitely won't here. The reason they usually won't is that most options trade above their intrinsic value (the amount that they're in the money). In your example, the options aren't in the money at all. The stock is trading at 120, and the option gives the owner the right to buy at 120. Put another way, exercising the option lets the owner buy the stock for the exact same price anyone with no options can in the market. So, if the call has any value whatsoever, exercising it is irrational; the owner would be better off selling the call and buying the stock in the market.\"", "title": "" }, { "docid": "323768", "text": "\"(See also the question How many stocks I can exercise per stock warrant? and my comments there). Clearly, at the prices you quote, it does not seem sensible to exercise your warrants at the moment, since you can still by \"\"units\"\" (1 stock + 1/3 warrant) and bare stock at below the $11.50 it would cost you to exercise your warrant. So when would exercising a warrant become \"\"a sensible thing to do\"\"? Obviously, if the price of the bare stock (which you say is currently $10.12) were to sufficiently exceed $11.50, then it would clearly be worth exercising a warrant and immediately selling the stock you receive (\"\"sufficiently exceed\"\" to account for any dealing costs in selling the newly-acquired stock). However, looking more closely, $11.50 isn't the correct \"\"cut-off\"\" price. Consider three of the units you bought at $10.26 each. For $30.78 you received three shares of stock and one warrant. For an additional $11.50 ($42.28 in total) you can have a total of four shares of stock (at the equivalent of $10.57 each). So, if the price of the bare stock rises above $10.57, then it could become sensible to exercise one warrant and sell four shares of stock (again allowing a margin for the cost of selling the stock). The trading price of the original unit (1 stock + 1/3 warrant) shouldn't (I believe) directly affect your decision to exercise warrants, although it would be a factor in deciding whether to resell the units you've already got. As you say, if they are now trading at $10.72, then having bought them at $10.26 you would make a profit if sold. Curiously, unless I'm missing something, or the figures you quote are incorrect, the current price of the \"\"unit\"\" (1 stock + 1/3 warrant; $10.72) seems overpriced compared to the price of the bare stock ($10.12). Reversing the above calculation, if bare stock is trading at $10.12, then four shares would cost $40.48. Deducting the $11.50 cost-of-exercising, this would value three \"\"combined units\"\" at $28.98, or $9.66 each, which is considerably below the market price you quote. One reason the \"\"unit\"\" (1 stock + 1/3 warrant) is trading at $10.72 instead of $9.66 could be that the market believes the price of the bare share (currently $10.12) will eventually move towards or above $11.50. If that happens, the option of exercising warrants at $11.50 becomes more and more attractive. The premium presumably reflects this potential future benefit. Finally, \"\"Surely I am misunderstand the stock IPO's intent.\"\": presumably, the main intent of Social Capital was to raise as much money as possible through this IPO to fund their future activities. The \"\"positive view\"\" is that they expect this future activity to be profitable, and therefore the price of ordinary stock to go up (at least as far as, ideally way beyond) the $11.50 exercise price, and the offering of warrants will be seen as a \"\"thank you\"\" to those investors who took the risk of taking part in the IPO. A completely cynical view would be that they don't really care what happens to the stock price, but that \"\"offering free stuff\"\" (or what looks like \"\"free stuff\"\") will simply attract more \"\"punters\"\" to the IPO. In reality, the truth is probably somewhere between those two extremes.\"", "title": "" } ]
4733	Why does Yahoo! Finance report different prices for the same index?	[ { "docid": "309314", "text": "\"Are you sure you're using the same date range? If you're using Max, then you're not, as ^FTMC goes back to 12/1/1985 while ^GDAXI only goes back to 11/1/1990. If I enter a custom date range of 11/1/1990 through 10/24/2015, I get: and: which, other than the dates it chose to use as labels on the x-axes, look identical. (I tried to add the URLs of the charts, but it looks like the Yahoo! URLs don't include the comparison symbol, which makes them useless for this answer. They're easy enough to construct though, just add the secondary symbol using the Comparison button and set the date range using the calendar button.) On your PS, I don't know, as you can see by my charts it even chose different labels when the date ranges were identical (although at least it didn't scale different dates differently), so maybe it's trying to be \"\"smart\"\" and choose dates based on the total amount of data available for the primary symbol, which is different in the two cases.\"", "title": "" } ]	[ { "docid": "532616", "text": "At this time, Google Finance doesn't support historical return or dividend data, only share prices. The attributes for mutual funds such as return52 are only available as real-time data, not historical. Yahoo also does not appear to offer market return data including dividends. For example, the S&P 500 index does not account for dividends--the S&P ^SPXTR index does, but is unavailable through Yahoo Finance.", "title": "" }, { "docid": "159471", "text": "Why don't you look at the actual funds and etfs in question rather than seeking a general conclusion about all pairs of funds and etfs? For example, Vanguard's total stock market index fund (VTSAX) and ETF (VTI). Comparing the two on yahoo finance I find no difference over the last 5 years visually. For a different pair of funds you may find something very slightly different. In many cases the index fund and ETF will not have the same benchmark and fees so comparisons get a little more cloudy. I recall a while ago there was an article that was pointing out that at the time emerging market ETF's had higher fees than corresponding index funds. For this reason I think you should examine your question on a case-by-case basis. Index fund and ETF returns are all publicly available so you don't have to guess.", "title": "" }, { "docid": "317666", "text": "tl;dr: The CNN Money and Yahoo Finance charts are wildly inaccurate. The TD Ameritrade chart appears to be accurate and shows returns with reinvested dividends. Ignoring buggy data, CNN most likely shows reinvested dividends for quoted securities but not for the S&P 500 index. Yahoo most likely shows all returns without reinvested dividends. Thanks to a tip from Grade Eh Bacon, I was able to determine that TD Ameritrade reports returns with reinvested dividends (as it claims to do). Eyeballing the chart, it appears that S&P 500 grew by ~90% over the five year period the chart covers. Meanwhile, according to this S&P 500 return estimator, the five year return of S&P 500, with reinvested dividends, was 97.1% between July 2012 to July 2017 (vs. 78.4% raw returns). I have no idea what numbers CNN Money is working from, because it claims S&P 500 only grew about 35% over the last five years, which is less than half of the raw return. Ditto for Yahoo, which claims 45% growth. Even stranger still, the CNN chart for VFINX (an S&P 500 index fund) clearly shows the correct market growth (without reinvesting dividends from the S&P 500 index), so whatever problem exists is inconsistent: Yahoo also agrees with itself for VFINX, but comes in a bit low even if your assume no reinvestment of dividends (68% vs. 78% expected); I'm not sure if it's ever right. By way of comparison, TD's chart for VFINX seems to be consistent with its ABALX chart and with reality: As a final sanity check, I pulled historical ^GSPC prices from Yahoo Finance. It closed at $1406.58 on 27 Aug 2012 and $2477.55 on 28 Aug 2017, or 76.1% growth overall. That agrees with TD and the return calculator above, and disagrees with CNN Money (on ABALX). Worse, Yahoo's own charts (both ABALX and VFINX) disagree with Yahoo's own historical data.", "title": "" }, { "docid": "410123", "text": "\"To add on to the other answers, in asking why funds have different price points one might be asking why stocks aren't normalized so a unit price of $196 in one stock can be directly compared to the same price in another stock. While this might not make sense with AAPL vs. GOOG (it would be like comparing apples to oranges, pun intended, not to mention how would two different companies ever come to such an agreement) it does seem like it would make more sense when tracking an index. And in fact less agreement between different funds would be required as some \"\"natural\"\" price points exist such as dividing by 100 (like some S&P funds do). However, there are a couple of reasons why two different funds might price their shares of the same underlying index differently. Demand - If there are a lot of people wanting the issue, more shares might be issued at a lower price. Or, there might be a lot of demand centered on a certain price range. Pricing - shares that are priced higher will find fewer buyers, because it makes it harder to buy round lots (100 shares at $100/share is $10,000 while at $10/share it's only $1000). While not everyone buys stock in lots, it's important if you do anything with (standardized) options on the stock because they are always acting on lots. In addition, even if you don't buy round lots a higher price makes it harder to buy in for a specific amount because each unit share has a greater chance to be further away from your target amount. Conversely, shares that are priced too low will also find fewer buyers, because some holders have minimum price requirements due to low price (e.g. penny) stocks tending to be more speculative and volatile. So, different funds tracking the same index might pick different price points to satisfy demand that is not being filled by other funds selling at a different price point.\"", "title": "" }, { "docid": "405474", "text": "The difference is that Yahoo is showing the unadjusted price that the security traded for on that date, while google is adjusting for price splits. This means that Google is showing how much you would have had to pay to get what is now one share. Since 1979, JNJ has split 3-for-1 once, and 2-for-1 four times. 3x2x2x2x2 = 48. If you bought 1 share at that time, you would now have 48 shares today. Yahoo is showing a price of $66 for what was then 1 share. $66/48 = 1.375, which Google rounds to 1.38. You can see this if you get the prices from May 14-21, 1981. The stock split 3-for-1, and the price dropped from 108 to 36.38. Yahoo's adjusted close column has not been accurate since they re-wrote the Finance website. It now just represents the closing price. The other relevant field on Yahoo is the Adj. Close. This adjusts for splits, but also adjusts for dividends. Hence why this doesn't match either the Google or Yahoo numbers.", "title": "" }, { "docid": "317803", "text": "\"Maria, there are a few questions I think you must consider when considering this problem. Do fundamental or technical strategies provide meaningful information? Are the signals they produce actionable? In my experience, and many quantitative traders will probably say similar things, technical analysis is unlikely to provide anything meaningful. Of course you may find phenomena when looking back on data and a particular indicator, but this is often after the fact. One cannot action-ably trade these observations. On the other hand, it does seem that fundamentals can play a crucial role in the overall (typically long run) dynamics of stock movement. Here are two examples, Technical: suppose we follow stock X and buy every time the price crosses above the 30 day moving average. There is one obvious issue with this strategy - why does this signal have significance? If the method is designed arbitrarily then the answer is that it does not have significance. Moreover, much of the research supports that stocks move close to a geometric brownian motion with jumps. This supports the implication that the system is meaningless - if the probability of up or down is always close to 50/50 then why would an average based on the price be predictive? Fundamental: Suppose we buy stocks with the best P/E ratios (defined by some cutoff). This makes sense from a logical perspective and may have some long run merit. However, there is always a chance that an internal blowup or some macro event creates a large loss. A blended approach: for sake of balance perhaps we consider fundamentals as a good long-term indication of growth (what quants might call drift). We then restrict ourselves to equities in a particular index - say the S&P500. We compare the growth of these stocks vs. their P/E ratios and possibly do some regression. A natural strategy would be to sell those which have exceeded the expected return given the P/E ratio and buy those which have underperformed. Since all equities we are considering are in the same index, they are most likely somewhat correlated (especially when traded in baskets). If we sell 10 equities that are deemed \"\"too high\"\" and buy 10 which are \"\"too low\"\" we will be taking a neutral position and betting on convergence of the spread to the market average growth. We have this constructed a hedged position using a fundamental metric (and some helpful statistics). This method can be categorized as a type of index arbitrage and is done (roughly) in a similar fashion. If you dig through some data (yahoo finance is great) over the past 5 years on just the S&P500 I'm sure you'll find plenty of signals (and perhaps profitable if you calibrate with specific numbers). Sorry for the long and rambling style but I wanted to hit a few key points and show a clever methods of using fundamentals.\"", "title": "" }, { "docid": "564338", "text": "http://www.pacificrubiales.com/investor-relations/reports.html does have financial reports on their website for the example you list. There is the potential for some data to not be easily imported into a format that Yahoo! Finance uses would be my guess for why some data may be missing though an alternative explanation for some companies would be that they may not have been around for a long enough time period to report this information,e.g. if the company is a spin-off of an existing company.", "title": "" }, { "docid": "148721", "text": "\"Funds which track the same index may have different nominal prices. From an investors point of view, this is not important. What is important is that when the underlying index moves by a given percentage, the price of the tracking funds also move by an equal percentage. In other words, if the S&P500 rises by 5%, then the price of those funds tracking the S&P500 will also rise by 5%. Therefore, investing a given amount in any of the tracking funds will produce the same profit or loss, regardless of the nominal prices at which the individual funds are trading. To see this, use the \"\"compare\"\" function available on the popular online charting services. For example, in Google finance call up a chart of the S&P500 index, then use the compare textbox to enter the codes for the various ETFs tracking the S&P500. You will see that they all track the S&P500 equally so that your relative returns will be equal from each of the tracking funds. Any small difference in total returns will be attributable to management fees and expenses, which is why low fees are so important in passive investing.\"", "title": "" }, { "docid": "100485", "text": "On Monday, the 27th of June 2011, the XIV ETF underwent a 10:1 share split. The Yahoo Finance data correctly shows the historic price data adjusted for this split. The Google Finance data does not make the adjustment to the historical data, so it looks like the prices on Google Finance prior to 27 June 2011 are being quoted at 10 times what they should be. Coincidentally, the underlying VIX index saw a sudden surge on the Friday (24 June) and continued on the Monday (27 June), the date that the split took effect. This would have magnified the bearish moves seen in the historic price data on the XIV ETF. Here is a link to an article detailing the confusion this particular share split caused amongst investors. It appears that Google Finance was not the only one to bugger it up. Some brokers failed to adjust their data causing a lots of confusion amongst clients with XIV holdings at the time. This is a recurring problem on Google Finance, where the historic price data often (though not always) fails to account for share splits.", "title": "" }, { "docid": "343042", "text": "I work on a buy-side firm, so I know how these small data issues can drive us crazy. Hope my answer below can help you: Reason for price difference: 1. Vendor and data source Basically, data providers such as Google and Yahoo redistribute EOD data by aggregating data from their vendors. Although the raw data is taken from the same exchanges, different vendors tend to collect them through different trading platforms. For example, Yahoo, is getting stock data from Hemscott (which was acquired by Morningstar), which is not the most accurate source of EOD stocks. Google gets data from Deutsche Börse. To make the process more complicated, each vendor can choose to get EOD data from another EOD data provider or the exchange itself, or they can produce their own open, high, low, close and volume from the actual trade tick-data, and these data may come from any exchanges. 2. Price Adjustment For equities data, the re-distributor usually adjusts the raw data by applying certain customized procedures. This includes adjustment for corporate actions, such as dividends and splits. For futures data, rolling is required, and back-ward and for-warding rolling can be chosen. Different adjustment methods can lead to different price display. 3. Extended trading hours Along with the growth of electronic trading, many market tends to trade during extended hours, such as pre-open and post-close trading periods. Futures and FX markets even trade around the clock. This leads to another freedom in price reporting: whether to include the price movement during the extended trading hours. Conclusion To cross-verify the true price, we should always check the price from the Exchange where the asset is actually traded. Given the convenience of getting EOD data nowadays, this task should be easy to achieve. In fact, for professional traders and investors alike, they will never reply price on free providers such as Yahoo and Google, they will most likely choose Bloomberg, Reuters, etc. However, for personal use, Yahoo and Google should both be good choices, and the difference is small enough to ignore.", "title": "" }, { "docid": "189341", "text": "Another possibly more flexible option is Yahoo finance here is an example for the dow.. http://finance.yahoo.com/q/hp?s=%5EDJI&a=9&b=1&c=1928&d=3&e=10&f=2012&g=d&z=66&y=0 Some of the individual stocks you can dl directly to a spreadsheet (not sure why this isn't offer for indexs but copy and paste should work). http://finance.yahoo.com/q/hp?s=ACTC.OB+Historical+Prices", "title": "" }, { "docid": "553377", "text": "\"You could use any of various financial APIs (e.g., Yahoo finance) to get prices of some reference stock and bond index funds. That would be a reasonable approximation to market performance over a given time span. As for inflation data, just googling \"\"monthly inflation data\"\" gave me two pages with numbers that seem to agree and go back to 1914. If you want to double-check their numbers you could go to the source at the BLS. As for whether any existing analysis exists, I'm not sure exactly what you mean. I don't think you need to do much analysis to show that stock returns are different over different time periods.\"", "title": "" }, { "docid": "365799", "text": "The correct p/e for bp.l is 5.80. Bp.l is on the London stock exchange and prices are in local currency. The share price of 493 is reported in pence (not dollars). The EPS is reported in pounds. Using .85 pounds = 85 pence, you calculate the EPS as follows: 493.40/85 = 5.80 PE Yahoo totally screwed up. They converted the .85 pounds into US dollars ($1.34) but didn't convert the 493 pence. By using the 493 as dollars, they got 493.9/1.34 = 368 pe! Notice that Yahoo reports the American Depository Shares (symbol 'BP') with an EPS of $8.06. That correctly reflects that there are 6 shares of BP.l per ADS (1.34 * 6 = 8.04). But why is the share price listed at $46.69? Well... 493 GBp (pence) = 4.93 pounds 4.93 pounds = 7.73 USD 7.73 USD * 6 shares per ADS = 46.38 USD", "title": "" }, { "docid": "91430", "text": "\"What you need to do is go to yahoo finance and look at different stock's P/E ratios. You'll quickly see that the stocks can be sorted by this number. It would be an interesting exercise to get an idea of why P/E isn't a fixed number, how certain industries cluster around a certain number, but even this isn't precise. But, it will give you an idea as to why your question has no answer. \"\"Annual earnings are $1. What is the share price?\"\" \"\"Question has no answer\"\"\"", "title": "" }, { "docid": "173967", "text": "The S&P500 is an index, not an investment by itself. The index lists a large number of stocks, and the value of the index is the price of all the stocks added together. If you want to make an investment that tracks the S&P500, you could buy some shares of each stock in the index, in the same proportions as the index. This, however, is impractical for just about everyone. Index mutual funds provide an easy way to make this investment. SPY is an ETF (exchange-traded mutual fund) that does the same thing. An index CFD (contract for difference) is not the same as an index mutual fund. There are a number of differences between investing in a security fund and investing in a CFD, and CFDs are not available everywhere.", "title": "" }, { "docid": "215540", "text": "\"There are several reasons to pay for data instead of using Yahoo Finance, although these reasons don't necessarily apply to you if you're only planning to use the data for personal use. Yahoo will throttle you if you attempt to download too much data in a short time period. You can opt to use the Yahoo Query Language (YQL), which does provide another interface to their financial data apart from simply downloading the CSV files. Although the rate limit is higher for YQL, you may still run into it. An API that a paid data provider exposes will likely have higher thresholds. Although the reliability varies throughout the site, Yahoo Finance isn't considered the most reliable of sources. You can't beat free, of course, but at least for research purposes, the Center for Research in Security Prices (CRSP) at UChicago and Wharton is considered the gold standard. On the commercial side, data providers like eSignal, Bloomberg, Reuters also enjoy widespread popularity. Although both the output from YQL and Yahoo's current CSV output are fairly standard, they won't necessarily remain that way. A commercial API is basically a contract with the data provider that they won't change the format without significant prior notice, but it's reasonable to assume that if Yahoo wanted to, they could make minor changes to the format and break many commercial applications. A change in Yahoo's format would likely break many sites or applications too, but their terms of use do state that Yahoo \"\"may change, suspend, or discontinue any aspect of the Yahoo! Finance Modules at any time, including the availability of any Yahoo! Finance Modules. Yahoo! may also impose limits on certain features and services or restrict your access to parts or all of the Yahoo! Finance Modules or the Yahoo! Web site without notice or liability.\"\" If you're designing a commercial application, a paid provider will probably provide technical support for their API. According to Yahoo Finance's license terms, you can't use the data in a commercial application unless you specifically use their \"\"badges\"\" (whatever those are). See here. In this post, a Yahoo employee states: The Finance TOS is fairly specific. Redistribution of data is only allowed if you are using the badges the team has created. Otherwise, you can use YQL or whatever method to obtain data for personal use. The license itself states that you may not: sell, lease, or sublicense the Yahoo! Finance Modules or access thereto or derive income from the use or provision of the Yahoo! Finance Modules, whether for direct commercial or monetary gain or otherwise, without Yahoo!'s prior, express, written permission In short, for personal use, Yahoo Finance is more than adequate. For research or commercial purposes, a data provider is a better option. Furthermore, many commercial applications require more data than Yahoo provides, e.g. tick-by-tick data for equities, derivatives, futures, data on mergers, etc., which a paid data source will likely provide. Yahoo is also known for inaccuracies in its financial statements; I can't find any examples at the moment, but I had a professor who enjoyed pointing out flaws in the 10K's that he had come across. I've always assumed this is because the data were manually entered, although I would assume EDGAR has some method for automatic retrieval. If you want data that are guaranteed to be accurate, or at least have a support contract associated with them so you know who to bother if it isn't, you'll need to pay for it.\"", "title": "" }, { "docid": "32282", "text": "As others have pointed out, the value of Apple's stock and the NASDAQ are most likely highly correlated for a number of reasons, not least among them the fact that Apple is part of the NASDAQ. However, because numerous factors affect the entire market, or at least a significant subset of it, it makes sense to develop a strategy to remove all of these factors without resorting to use of an index. Using an index to remove the effect of these factors might be a good idea, but you run the risk of potentially introducing other factors that affect the index, but not Apple. I don't know what those would be, but it's a valid theoretical concern. In your question, you said you wanted to subtract them from each other, and only see an Apple curve moving around a horizontal line. The basic strategy I plan to use is similar but even simpler. Instead of graphing Apple's stock price, we can plot the difference between its stock price on business day t and business day t-1, which gives us this graph, which is essentially what you're looking for: While this is only the preliminaries, it should give you a basic idea of one procedure that's used extensively to do just what you're asking. I don't know of a website that will automatically give you such a metric, but you could download the price data and use Excel, Stata, etc. to analyze this. The reasoning behind this methodology builds heavily on time series econometrics, which for the sake of simplicity I won't go into in great detail, but I'll provide a brief explanation to satisfy the curious. In simple econometrics, most time series are approximated by a mathematical process comprised of several components: In the simplest case, the equations for a time series containing one or more of the above components are of the form that taking the first difference (the procedure I used above) will leave only the random component. However, if you want to pursue this rigorously, you would first perform a set of tests to determine if these components exist and if differencing is the best procedure to remove those that are present. Once you've reduced the series to its random component, you can use that component to examine how the process underlying the stock price has changed over the years. In my example, I highlighted Steve Jobs' death on the chart because it's one factor that may have led to the increased standard deviation/volatility of Apple's stock price. Although charts are somewhat subjective, it appears that the volatility was already increasing before his death, which could reflect other factors or the increasing expectation that he wouldn't be running the company in the near future, for whatever reason. My discussion of time series decomposition and the definitions of various components relies heavily on Walter Ender's text Applied Econometric Time Series. If you're interested, simple mathematical representations and a few relevant graphs are found on pages 1-3. Another related procedure would be to take the logarithm of the quotient of the current day's price and the previous day's price. In Apple's case, doing so yields this graph: This reduces the overall magnitude of the values and allows you to see potential outliers more clearly. This produces a similar effect to the difference taken above because the log of a quotient is the same as the difference of the logs The significant drop depicted during the year 2000 occurred between September 28th and September 29th, where the stock price dropped from 26.36 to 12.69. Apart from the general environment of the dot-com bubble bursting, I'm not sure why this occurred. Another excellent resource for time series econometrics is James Hamilton's book, Time Series Analysis. It's considered a classic in the field of econometrics, although similar to Enders' book, it's fairly advanced for most investors. I used Stata to generate the graphs above with data from Yahoo! Finance: There are a couple of nuances in this code related to how I defined the time series and the presence of weekends, but they don't affect the overall concept. For a robust analysis, I would make a few quick tweaks that would make the graphs less appealing without more work, but would allow for more accurate econometrics.", "title": "" }, { "docid": "313421", "text": "\"The Dow Jones Industrial Average (DJIA) is a Price-weighted index. That means that the index is calculated by adding up the prices of the constituent stocks and dividing by a constant, the \"\"Dow divisor\"\". (The value of the Dow divisor is adjusted from time to time to maintain continuity when there are splits or changes in the roster.) This has the curious effect of giving a member of the index influence proportional to its share price. That is, if a stock costing $100 per share goes up by 1%, that will change the index by 10 times as much as if a stock costing $10 per share goes up by the same 1%. Now look at the price of Google. It's currently trading at just a whisker under $700 per share. Most of the other stocks in the index trade somewhere between $30 and $150, so if Google were included in the index it would contribute between 5 and 20 times the weight of any other stock in the index. That means that relatively small blips in Google's price would completely dominate the index on any given day. Until June of 2014, Apple was in the same boat, with its stock trading at about $700 per share. At that time, Apple split its stock 7:1, and after that its stock price was a little under $100 per share. So, post-split Apple might be a candidate to be included in the Dow the next time they change up the components of the index. Since the Dow is fixed at 30 stocks, and since they try to keep a balance between different sectors, this probably wouldn't happen until they drop another technology company from the lineup for some reason. (Correction: Apple is in the DJIA and has been for a little over a year now. Mea culpa.) The Dow's price-weighting is unusual as stock indices go. Most indices are weighted by market capitalization. That means the influence of a single company is proportional to its total value. This causes large companies like Apple to have a lot of influence on those indices, but since market capitalization isn't as arbitrary as stock price, most people see that as ok. Also, notice that I said \"\"company\"\" and not \"\"stock\"\". When a company has multiple classes of share (as Google does), market-cap-weighted indices include all of the share classes, while the Dow has no provision for such situations, which is another, albeit less important, reason why Google isn't in the Dow. (Keep this in mind the next time someone offers you a bar bet on how many stocks are in the S&P 500. The answer is (currently) 505!) Finally, you might be wondering why the Dow uses such an odd weighting in its calculations. The answer is that the Dow averages go back to 1896, when Charles Dow used to calculate the averages by hand. If your only tools are a pencil and paper, then a price-weighted index with only 30 stocks in it is a lot easier to calculate than a market-cap-weighted index with hundreds of constituents. About the Dow Jones Averages. Dow constituents and prices Apple's stock price chart. The split in 2014 is marked. (Note that prices before the split are retroactively adjusted to show a continuous curve.)\"", "title": "" }, { "docid": "591089", "text": ".INX (the S&P 500 index itself) does not include reinvested dividens. You can figure total return by going to Yahoo finance, historical data. Choose the start year, and end year. You should find that data for SPY (going back to 1993) will show an adjusted close, and takes dividends into account. This isn't perfect as SPY has a .09% expense ratio, but it's better than just the S&P index. One of the more popular Dow ETF is DIA, this will let you similarly track the Dow while accounting for dividends.", "title": "" }, { "docid": "477162", "text": "The GuruFocus Link is just reporting the high and low price of the quarter. Price Range (Average) – The estimated trade prices. The average price is calculated from the time weighted average during the period. If no price range is shown, the trade prices are estimated trade prices, which are more accurate estimates. AAPL: $420.05 - $549.03 ($467.26) The numbers for the high and low match what I found for AAPL on Yahoo Finance. Keep in mind their definition uses estimate 3 times.", "title": "" }, { "docid": "239137", "text": "If you use Google Finance, you will get incorrect results because Google Finance does not show the dividend history. Since your requirement is that dividends are re-invested, you should use Yahoo Finance instead, downloading the historical 'adjusted' price.", "title": "" }, { "docid": "107462", "text": "So, why or why should I not invest in the cheaper index fund? They are both same, one is not cheaper than other. You get something that is worth $1000. To give a simple illustration; There is an item for $100, Vanguard creates 10 Units out of this so price per unit is $10. Schwab creates 25 units out of this, so the per unit price is $4. Now if you are looking at investing $20; with Vanguard you would get 2 units, with Schwab you would get 5 units. This does not mean one is cheaper than other. Both are at the same value of $20. The Factors you need to consider are; Related question What differentiates index funds and ETFs?", "title": "" }, { "docid": "24979", "text": "There is most likely an error in the WSJ's data. Yahoo! Finance reports the P/E on the Russell 2000 to be 15 as of 8/31/11 and S&P 500 P/E to be 13 (about the same as WSJ). Good catch, though! E-mail WSJ, perhaps they will be grateful.", "title": "" }, { "docid": "532178", "text": "\"It's almost like why don't you wake up in the morning feeling exactly like you slept the earlier night? yeah, once in a while that'll happen, but it's not designed to be that way. Stuff happens. The close of the stock is what happened at 4 PM (for US stocks). The \"\"open\"\" is simply the first price ever, or an open price auction like NimChimpsky said. Most things that trade have an open/close cycle, even what seemingly trades all the time (some markets trade 23 hours). Forex trades in different exchanges which have overlapping timing but each market will have an open, high, low and close for each day - for what is the same underlying currency. Also, it's not exactly true that close<>open. Take the GS chart, Oct 1 2010 and Oct 4 2010 (there was a weekend in between). The Oct 1 close was the same as the Oct 4 open. Note that Oct 4 was a down day so it's in red - the open is the upper end of the body (not including the wick), and Oct 1 was an up day so its close was the upper end too. (Candles are drawn so that the open ends of the wicks are the High and Low of the period respectively, and the lower end of the body is the open if it was an up-day, meaning the stock closed higher than it opened, and the body in coloured green below. If the stock went down that day from the open, the body's in red and the lower end is the close. Vice-versa for the other end) The way to get to this: Go to yahoo finance, choose a stock, go to historical prices, click download data (you should have about 10 years of data), paste into excel, insert a formula to check if prev day's close = current day's open, and I'm sure you'll see at least one instance per stock.\"", "title": "" }, { "docid": "181909", "text": "\"The Yahoo Finance API is no longer available, so Finance::Quote needs to point at something else. Recent versions of Finance::Quote can use AlphaVantage as a replacement for the Yahoo Finance API, but individual users need to acquire and input an AlphaVantage API key. Pretty decent documentation for how to this is available at the GnuCash wiki. Once you've followed the directions on the wiki and set the API key, you still need to tell each individual security to use AlphaVantage rather than Yahoo Finance: As a warning, I've been having intermittent trouble with AlphaVantage. From the GnuCash wiki: Be patient. Alphavantage does not have the resources that Yahoo! did and it is common for quote requests to time out, which GnuCash will present as \"\"unknown error\"\". I've certainly been experiencing those errors, though not always.\"", "title": "" }, { "docid": "546379", "text": "Google Finance and Yahoo Finance have been transitioning their API (data interface) over the last 3 months. They are currently unreliable. If you're just interested in historical price data, I would recommend either Quandl or Tiingo (I am not affiliated with either, but I use them as data sources). Both have the same historical data (open, close, high, low, dividends, etc.) on a daily closing for thousands of Ticker symbols. Each service requires you to register and get a unique token. For basic historical data, there is no charge. I've been using both for many months and the data quality has been excellent and API (at least for python) is very easy! If you have an inclination for python software development, you can read about the drama with Google and Yahoo finance at the pandas-datareader group at https://github.com/pydata/pandas-datareader.", "title": "" }, { "docid": "357685", "text": "The big websites, Yahoo and the like, only give the 10 biggest positions of any fund. Download the annual report of the fund, go to page 18, you will find the positions on the 31st of December. However the actual positions could be different. The same applies to all funds. You need the annual report.", "title": "" }, { "docid": "66753", "text": "\"Asking why the p/e was so high is best answered \"\"because reported earnings were so low\"\". Recall that the S&P500 bottomed in early March 2009 when the panic of the financial crisis reached exhaustion. As noted on the page you have linked, the reported p/e ratios are computed using reported earnings from the trailing twelve months. During those twelve months the banks were writing down all of the bad debt associated with the mortgage backed securities that has lost so much value. This meant that the banks were reporting negative earnings. Since the financial sector is a large part of the S&P500, this alone had an enormous effect on the index p/e. However, the problem was compounded by a general collapse in earnings across the economy as consumers reacted to the resulting uncertainty. The same site reports earnings for the previous years at $17.11 for the S&P500, compared to $76.17 for the year prior to 2008. That is a collapse of about 78% in earnings. Although the S&P500 has suffered badly during this time, stock market investors being forward looking were starting to price in improved earnings by May 2009. Indeed, the S&P500 was up about 33% in just two months, from its low in March2009 to mid May2009. Thus, by May of 2009 prices were not suffering to the same extent as reported trailing earnings. This would account for the anomalous p/e value reporting in May2009.\"", "title": "" }, { "docid": "535343", "text": "Yahoo Finance's Historical Prices section allows you to look up daily historical quotes for any given stock symbol, you don't have to hit a library for this information. Your can choose a desired time frame for your query, and the dataset will include High/Low/Close/Volume numbers. You can then download a CSV version of this report and perform additional analysis in a spreadsheet of your choice. Below is Twitter report from IPO through yesterday: http://finance.yahoo.com/q/hp?s=TWTR&a=10&b=7&c=2013&d=08&e=23&f=2014&g=d", "title": "" }, { "docid": "465536", "text": "\"P/E is Price divided by Earnings Per Share (EPS). P/E TTM is Price divided by the actual EPS earned over the previous 12 months - hence \"\"Trailing Twelve Month\"\". In Forward P/E is the \"\"E\"\" is the average of analyst expectations for the next year in EPS. Now, as to what's being displayed. Yahoo shows EPS to be 1.34. 493.90/1.34 = P/E of 368.58 Google shows EPS to be 0.85. 493.40/0.85 = P/E of 580.47 (Prices as displayed, respectively) So, by the info that they are themselves displaying, it's Google, not Yahoo, that's displaying the wrong P/E. Note that the P/E it is showing is 5.80 -- a decimal misplacement from 580 Note that CNBC shows the Earnings as 0.85 as well, and correctly show the P/E as 580 http://data.cnbc.com/quotes/BP.L A quick use of a currency calculator reveals a possible reason why EPS is listed differently at yahoo. 0.85 pounds is 1.3318 dollars, currently. So, I think the Yahoo EPS listing is in dollars. A look at the last 4 quarters on CNBC makes that seem reasonable: http://data.cnbc.com/quotes/BP.L/tab/5 those add up to $1.40.\"", "title": "" } ]
5a74ebcc55429974ef308c97	Stefan Persson played home games in what borough while in the NHL?	[ { "docid": "6532262", "text": "Eric Stefan Persson (born 22 December 1954, in Bjurholm, Sweden) is a Swedish professional ice hockey executive and former player. He is the general manager of Borås HC hockey club in Sweden. Persson played for nine seasons with the New York Islanders of the National Hockey League (NHL), where he was a member of four Stanley Cup championship teams.", "title": "" }, { "docid": "66880", "text": "The New York Islanders are a professional ice hockey team based in New York City. They are members of the Metropolitan Division of the Eastern Conference of the National Hockey League (NHL). The team plays its home games at Barclays Center, located in the borough of Brooklyn. The Islanders are one of three NHL franchises in the New York metropolitan area, along with the New Jersey Devils and New York Rangers, and their fan base resides primarily on Long Island.", "title": "" } ]	[ { "docid": "9447451", "text": "Stefan Persson (born October 26, 1974) was a Swedish Bandy player who played for Hammarby IF Bandy as a defender. Stefan was brought up by Selångers SK where he stayed until the club were no longer strong, moving then to Hammarby. He retired in autumnn of 2008 and became the assistant coach of Hammarby.", "title": "" }, { "docid": "15574244", "text": "Stefan Rolf Bergkvist (born 10 March 1975 in Leksand, Sweden) is a Swedish professional ice hockey defenceman. He was drafted in the first round, twenty-sixth overall, of the 1993 NHL Entry Draft by the Pittsburgh Penguins and played seven games in the NHL with them.", "title": "" }, { "docid": "10246351", "text": "Lars Ricard Persson (born August 24, 1969) is a Swedish professional ice hockey player. Persson played in the NHL with the New Jersey Devils, St. Louis Blues, and Ottawa Senators. Persson is currently with SG Cortina of the Serie A. He has a daughter named Hannah Persson.", "title": "" }, { "docid": "1267629", "text": "Carl Stefan Erling Persson (] ; born 4 October 1947) is a Swedish business magnate. In March 2013, Forbes reported Persson's net worth as $28 billion making him the richest of Sweden's 12 billionaires and the 17th richest person in the world. Persson is the chairman and main shareholder in fashion company H&M, which was founded by his father Erling Persson in 1947. Persson took over the company from his father in 1982 and served as its manager until 1998. Persson also owns a substantial stake in the Swedish technology company Hexagon AB. Through his privately held real estate company Ramsbury Invest, Persson owns a large number of properties in London, Paris and Stockholm.", "title": "" }, { "docid": "6162630", "text": "Scott Scissons (born October 29, 1971 in Saskatoon, Saskatchewan) is a former Canadian professional ice hockey player. Currently lot manager of Best Buy Homes and head coach of midget AaA Saskatoon Blazers. He was drafted in the first round, sixth overall, by the New York Islanders in the 1990 NHL Entry Draft. While a high percentage of players selected in the first round of that draft went on to productive NHL careers, Scissons was one of the few busts, playing just two regular season NHL games (none of the other top eight picks in the 1990 draft played fewer than 909 games in the NHL) and one playoff game, going scoreless in all.", "title": "" }, { "docid": "859195", "text": "The 1999 NHL Entry Draft was held on June 26 at the FleetCenter in Boston, Massachusetts. According to \"Sports Illustrated\" and other sports news agencies, at the time the 1999 draft was considered one of the deepest in talent in years, headed by Patrik Stefan and the Sedin twins. However, the overall impact in the NHL hasn't matched those of the neighboring drafts. An example of this one is how many first round picks have played the equivalent of an entire regular season ten seasons after the 1999 draft; only 16 out of 28 first round picks in 1999 have played 82 NHL games, while the same statistic applies to 23 out of 27 players in 1998 and 21 out of 30 players in 2000. In addition, while the Sedin twins have excelled in the NHL, only Barret Jackman and Martin Havlat were still active players of the other 26 first-round picks in the NHL 15 years after the draft. The team that originally held the first overall pick, the Tampa Bay Lightning, traded out of the first round altogether in the trading carousel used to select the Sedins.", "title": "" }, { "docid": "40223454", "text": "John Persson (born May 18, 1992) is a Swedish professional ice hockey player. He is currently playing for Mora IK in the Swedish Hockey League (SHL). Persson was selected by the Islanders in the 5th round (125th overall) of the 2011 NHL Entry Draft.", "title": "" }, { "docid": "9267669", "text": "Jan Stefan Persson (born February 3, 1967 in Malmö, Skåne) is a former freestyle swimmer from Sweden. His best result is a fourth place on 1500m Freestyle at the European LC Championships 1987 in Strasbourg.", "title": "" }, { "docid": "39153670", "text": "The 2014 NHL Heritage Classic was an outdoor regular season National Hockey League (NHL) game held indoor, part of the Heritage Classic series of outdoor NHL ice hockey games in Canada. It took place on March 2, 2014, in BC Place in Vancouver, with the Ottawa Senators facing off against the home team Canucks. It is the first \"outdoor\" game to be played in what technically is an indoor stadium, albeit one of a larger capacity than a typical NHL arena; BC Place is a retractable roof venue, and it is unknown if the stadium has the capabilities to keep its roof open during inclement weather (several stadiums of the type explicitly cannot be kept open in such an environment due to drainage concerns). The game was televised nationally in Canada on CBC and nationally in the United States on NBCSN.", "title": "" }, { "docid": "53498025", "text": "The 2018 NHL Winter Classic is an upcoming regular season outdoor National Hockey League (NHL) game that is scheduled for January 1, 2018. The game will feature the Buffalo Sabres taking on the New York Rangers at Citi Field in the New York City borough of Queens, home of Major League Baseball's New York Mets. This will be the second Winter Classic for each team, following the Rangers' appearance in the 2012 event and the Sabres' in 2008. It will be also the Rangers' fourth outdoor game, having also appeared in the 2014 Stadium Series.", "title": "" }, { "docid": "42889941", "text": "The 1988 Hockey East Men's Ice Hockey Tournament was the 4th Tournament in the history of the conference. It was played between March 3 and March 11, 1989. Quarterfinal and semifinal games were played at home team campus sites, while the final game was played at the Boston Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. This was the final year the Hockey East championship was decided at a home venue to one of its member teams . By winning the tournament, Northeastern received the Hockey East's automatic bid to the 1988 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39301645", "text": "The 2006 Hockey East Men's Ice Hockey Tournament was the 22nd Tournament in the history of the conference. It was played between March 9 and March 18, 2006. Quarterfinal games were played at home team campus sites, while the final four games were played at the TD Banknorth Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston University received the Hockey East's automatic bid to the 2006 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39472719", "text": "The 1999 Hockey East Men's Ice Hockey Tournament was the 15th Tournament in the history of the conference. It was played between March 11 and March 20, 1999. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston College received the Hockey East's automatic bid to the 1999 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39505892", "text": "The 2000 Hockey East Men's Ice Hockey Tournament was the 16th Tournament in the history of the conference. It was played between March 9 and March 18, 2000. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Maine received the Hockey East's automatic bid to the 2000 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39550346", "text": "The 2001 Hockey East Men's Ice Hockey Tournament was the 17th Tournament in the history of the conference. It was played between March 8 and March 17, 2001. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston College received the Hockey East's automatic bid to the 2001 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39658412", "text": "The 2002 Hockey East Men's Ice Hockey Tournament was the 18th Tournament in the history of the conference. It was played between March 7 and March 16, 2002. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament New Hampshire received the Hockey East's automatic bid to the 2002 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39712095", "text": "The 2003 Hockey East Men's Ice Hockey Tournament was the 19th Tournament in the history of the conference. It was played between March 6 and March 17, 2003. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament New Hampshire received the Hockey East's automatic bid to the 2003 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39752357", "text": "The 2004 Hockey East Men's Ice Hockey Tournament was the 20th Tournament in the history of the conference. It was played between March 11 and March 20, 2004. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament Maine received the Hockey East's automatic bid to the 2004 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39804193", "text": "The 2005 Hockey East Men's Ice Hockey Tournament was the 21st Tournament in the history of the conference. It was played between March 10 and March 19, 2005. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament Boston College received the Hockey East's automatic bid to the 2005 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39983888", "text": "The 2007 Hockey East Men's Ice Hockey Tournament was the 23rd Tournament in the history of the conference. It was played between March 8 and March 17, 2007. Quarterfinal games were played at home team campus sites, while the final four games were played at the TD Banknorth Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament Boston College received the Hockey East's automatic bid to the 2007 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42807840", "text": "The 1998 Hockey East Men's Ice Hockey Tournament was the 14th tournament in the history of the conference. It was played between March 12 and March 21, 1998. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston College received the Hockey East's automatic bid to the 1998 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42814718", "text": "The 1997 Hockey East Men's Ice Hockey Tournament was the 13th Tournament in the history of the conference. It was played between March 6 and March 15, 1997. Quarterfinal games were played at home team campus sites, while the final four games were played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston University received the Hockey East's automatic bid to the 1997 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42816650", "text": "The 1996 Hockey East Men's Ice Hockey Tournament was the 12th tournament in the history of the conference. It was played between March 7 and March 16, 1996. Quarterfinal games were played at home team campus sites, while the final four games were, for the first time, played at the Fleet Center in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Providence received the Hockey East's automatic bid to the 1996 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42856763", "text": "The 1994 Hockey East Men's Ice Hockey Tournament was the 10th Tournament in the history of the conference. It was played between March 11 and March 19, 1994. Quarterfinal games were played at home team campus sites, while the final four games were played at the Boston Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston University received the Hockey East's automatic bid to the 1994 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42862148", "text": "The 1993 Hockey East Men's Ice Hockey Tournament was the 9th Tournament in the history of the conference. It was played between March 12 and March 20, 1993. Quarterfinal games were played at home team campus sites, while the final four games were played at the Boston Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Maine received the Hockey East's automatic bid to the 1993 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42862392", "text": "The 1992 Hockey East Men's Ice Hockey Tournament was the 8th Tournament in the history of the conference. It was played between March 6 and March 14, 1992. Quarterfinal games were played at home team campus sites, while the final four games were played at the Boston Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Maine received the Hockey East's automatic bid to the 1992 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42864785", "text": "The 1991 Hockey East Men's Ice Hockey Tournament was the 7th Tournament in the history of the conference. It was played between February 27 and March 10, 1991. Quarterfinal games were played at home team campus sites, while the final four games were played at the Boston Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston University received the Hockey East's automatic bid to the 1991 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42890098", "text": "The 1987 Hockey East Men's Ice Hockey Tournament was the 3rd Tournament in the history of the conference. It was played between March 10 and March 16, 1987. Quarterfinal games were played at home team campus sites, while the final four games were, for the first time, played at the Boston Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston College received the Hockey East's automatic bid to the 1987 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "42839725", "text": "The 1995 Hockey East Men's Ice Hockey Tournament was the 11th Tournament in the history of the conference. It was played between March 7 and March 18, 1995. Play-in and quarterfinal games were played at home team campus sites, while the final four games were, for the final time, played at the Boston Garden in Boston, Massachusetts, the home venue of the NHL's Boston Bruins. By winning the tournament, Boston University received the Hockey East's automatic bid to the 1995 NCAA Division I Men's Ice Hockey Tournament.", "title": "" }, { "docid": "39326203", "text": "The Stadium Series is an event held by the National Hockey League (NHL) in which a regular-season hockey game is played outdoors. This event is distinct from the NHL Winter Classic and NHL Heritage Classic outdoor games, played on New Year's Day and in Canada respectively. The first Stadium Series was held in 2014 and consisted of seven teams participating in four games held in three venues. In 2015, only one game in the Stadium Series was held, while in 2016, two games were held. In 2017 it consisted of only one game. One game has been announced for 2018.", "title": "" } ]
5a79d89d5542994bb94570e9	How big is the swamp that the Stephen C Foster State Park is located in?	[ { "docid": "6238767", "text": "Stephen C. Foster State Park is an 80 acre state park located in the Okefenokee Swamp in Charlton County, Georgia. Situated on the banks of the Suwannee River, the park offers visitors several ways to explore the swamp's unique ecosystem.", "title": "" }, { "docid": "192632", "text": "The Okefenokee Swamp is a shallow, 438,000 acre , peat-filled wetland straddling the Georgia–Florida line in the United States. A majority of the swamp is protected by the Okefenokee National Wildlife Refuge and the Okefenokee Wilderness. The Okefenokee Swamp is considered to be one of the Seven Natural Wonders of Georgia. The Okefenokee is the largest \"blackwater\" swamp in North America.", "title": "" } ]	[ { "docid": "4064610", "text": "Stephen Foster Folk Culture Center State Park is a Florida State Park located in White Springs off U.S. 41, along the Suwannee River in north Florida.", "title": "" }, { "docid": "4264807", "text": "Big Bog State Recreation Area, a recent addition to the Minnesota state park system, is located on Minnesota State Highway 72, north of Waskish, Minnesota. It covers 9,459 acres (38.3 km), primarily swamps, bogs, and upland \"islands\".", "title": "" }, { "docid": "3720218", "text": "Fakahatchee Strand State Preserve is a Florida State Park just west of Copeland, Florida. It is located in the Fakahatchee Strand, a thread of forested strand (swamp) in Big Cypress, a section of the Florida Everglades off SR 29.", "title": "" }, { "docid": "3681742", "text": "Collier-Seminole State Park is a Florida State Park located on US 41, 17 mi south of Naples, Florida. The park is the home of a National Historic Mechanical Engineering Landmark, the Bay City Walking Dredge used to build the Tamiami Trail through the Everglades. The park includes of 6430 acre of mangrove swamp, cypress swamps, salt marshes, mangrove river estuaries, and pine flatwoods. Among the wildlife of the park are American alligators, raccoons, ospreys, and American white ibis. brown pelicans, wood storks, bald eagles, red-cockaded woodpeckers, American crocodiles, Florida black bears (\"Ursus americanus floridanus\") and Big Cypress fox squirrels (\"Sciurus niger avicennia\") also inhabit the park.", "title": "" }, { "docid": "28622510", "text": "Okefenokee Swamp Park , located near Waycross, Georgia, United States, is the northern most entry point to the Okefenokee National Wildlife Refuge. The Okefenokee Swamp, is the most extensive blackwater swamp in North America and covers over 438,000 acres. The Okefenokee Swamp Park, Inc., which began operation in October 1946, receives no federal or state funding and operates as a 501(c)(3) non-profit organization. Located six miles southeast from Waycross, Georgia, the park serves as a convenient access point to the \"Land of the Trembling Earth,\" and prides itself on being a leader in both Ecotourism and Education. The park allows visitors to get an casual and up-close look at some of the swamp's infamous residents such as the American Alligator, river otter, turtles, snakes, birds-of-prey, and more. Priding itself on allowing everyone to get a introduction into the Okefenokee Swamp, the Okefenokee Swamp Park allows visitors to take a boat ride, train ride, see a nature show and walk out to a 90-foot observation tower all in a 3-1/2 hours. A 45-minute boat ride winds down Indian trails to a 90-foot observation tower which is also accessible by a narrow, winding boardwalk. The \"Eye on Nature\" show gives visitors the opportunity to hear about, and see first-hand, some of the native snake species, as well as a touch a baby alligator. The Lady Suwannee train meanders through southern pine forests on the outskirts of the wetlands and visits Pioneer Island, where visitors can view and walk through a recreated early swamp homestead.", "title": "" }, { "docid": "8226678", "text": "Mt. Pisgah State Park is a 1302 acre Pennsylvania state park in Smithfield, Springfield, Troy and West Burlington Townships, Bradford County, Pennsylvania in the United States. The park is located almost exactly halfway between Troy and Towanda, along Pennsylvania State Route 3019, near U.S. Route 6, at the base of Mt. Pisgah. The park is bordered by Mill Creek, Mt. Pisgah County Park and State Game Land 289. Mill Creek which flows through the park has been dammed and forms Stephen Foster Lake a 75 acre man-made lake.", "title": "" }, { "docid": "46589315", "text": "The C.E. Foster House is a historic house on Skyline Drive (Arkansas Highway 88) in Queen Wilhelmina State Park, located in central western Arkansas. It is a rustic stone structure, with two parts connected by a breezeway, located just outside the park entrance on the north side of the highway. It was built in 1931 by Carlos Hill and Phil Lance, and sold soon afterward to C. E. Foster, an Oklahoma oil businessman, who bought it for use as a summer house. It is one of four houses built by Hill on Rich Mountain, and is the best-preserved of the two that survive. In the 1960s the house was operated as a tourist attraction known as the \"Wonder House\"; it was taken over by the state in 1971.", "title": "" }, { "docid": "51231640", "text": "C. Stephen Foster is an American ophthalmologist, known for his research and treatment of ocular inflammatory disease (OID) with immunomodulatory therapy. He has published over 700 peer reviewed journal articles and authored 3 textbooks in his field.", "title": "" }, { "docid": "2781381", "text": "My Old Kentucky Home State Park is a state park located in Bardstown, Kentucky. The park's centerpiece is Federal Hill, a farm owned by United States Senator John Rowan in 1795. During the Rowan family's occupation, the mansion became a meeting place for local politicians and hosted several visiting dignitaries. The farm is best known for its association with American composer Stephen Foster's anti-slavery ballad \"My Old Kentucky Home, Good Night\". Foster was a cousin of the Rowan family, and was likely inspired to write the ballad both by Harriet Beecher Stowe's anti-slavery novel Uncle Tom's Cabin and through imagery seen on visits to Federal Hill. After popularity of the song increased throughout the United States, Federal Hill was purchased by the Commonwealth of Kentucky, dedicated as a historic site, and renamed \"My Old Kentucky Home\" on July 4, 1923. Foster's song by the same name was made the state song of Kentucky in 1928. The Federal Hill mansion was featured on a U.S. postage stamp in 1992, and it is one of the symbols featured on the reverse of the Kentucky state quarter issued in 2001.", "title": "" }, { "docid": "22412587", "text": "Stephen Foster Memorial Day is a United States Federal Observance Day observed on January 13. According to 36 U.S.C. § 140, Stephen Foster Memorial Day celebrates the life of American songwriter Stephen Foster. The date commemorates date that Foster died. The law took effect on November 2, 1966, and the day was first observed in January 1967.", "title": "" }, { "docid": "52870465", "text": "Mullinger Swamp Conservation Park is a protected area in the Australian state of South Australia located in the state’s Limestone Coast in the gazetted locality of Kybybolite on the border with the state of Victoria about 25 km north-east of Naracoorte.", "title": "" }, { "docid": "631382", "text": "Merchants Millpond State Park is a North Carolina state park in Gates County, North Carolina, in the United States. Located near Gatesville, in North Carolina's coastal plain, it covers 3,447 acre around a 200-year-old, 700 acre millpond and Lassiter Swamp. Canoeing is one of the park's major attractions. Alligators live in its large cypress swamps.", "title": "" }, { "docid": "285234", "text": "\"Beautiful Dreamer\" is a parlor song by American songwriter Stephen Foster (1826–1864). It was published posthumously in March 1864, by Wm. A. Pond & Co. of New York. The first edition states on its title page that it is \"the last song ever written by Stephen C. Foster. Composed but a few days prior to his death.\" However, Carol Kimball, the author of \"Song\", points out that the first edition's copyright is dated 1862, which suggests, she writes, the song was composed and readied for publication two years before Foster's death. There are at least 20 songs, she observes, that claim to be Foster's last, and it is unknown which is indeed his last. The song is set in time with a broken chord accompaniment.", "title": "" }, { "docid": "13776890", "text": "Cat Tales Zoological Park is a USDA Licensed - Class C - Exhibitor (all zoos fall under this classification) that helps rescue and protect big cats. It is located in Spokane, Washington, United States. As of Winter 2015 they provided a home to 27 big cats, 2 black bears, and 7 parrots.", "title": "" }, { "docid": "103312", "text": "Hasties Swamp is a national park in Queensland, Australia, 1,371 km northwest of Brisbane. The swamp is located several kilometers south of the town of Atherton in Far North Queensland. The main feature of the park is a seasonal wetland. Part of the swamp was first declared a national park on 5 April 1980.", "title": "" }, { "docid": "8718597", "text": "Stephen F. Austin State Park is a state park in Texas, United States and is located in San Felipe, Austin County, west of Houston on the Brazos River.", "title": "" }, { "docid": "635961", "text": "Stephens State Park is a state park in the U.S. state of New Jersey. It is 805 acres in area, located in western Morris County, north of Hackettstown along the upper Musconetcong River. The park is operated and maintained by the New Jersey Division of Parks and Forestry.", "title": "" }, { "docid": "48156065", "text": "Morrison Foster (June 10, 1823May 14, 1904) was the older brother, business agent and biographer for Stephen Foster, a composer and lyricist of early American music. When Stephen Foster died at age 37, Morrison continued to manage Stephen's estate and acted as a mediator between music publishers and Stephen Foster's wife and daughter. Documents demonstrate his correspondence with publishers in his receipt of royalty payments on behalf of Stephen's heirs. Morrison also wrote the first biography of Stephen Foster. Morrison's daughter Evelyn Foster Mornewek, wrote an biography about her uncle, \"Chronicles of Stephen Foster's Family.\"", "title": "" }, { "docid": "15691498", "text": "Pigeon Swamp State Park is a 1078 acre New Jersey state park located on Deans Rhode Hall Road (Middlesex CR-610) in South Brunswick, in Middlesex County, New Jersey, United States. It is an undeveloped park, with a mix of habitats including open ponds and uplands hardwood forests. It also includes a good example of an inner coastal plain lowland deciduous hardwood forest. At one time, it was a major nesting site for passenger pigeons before they became extinct. It was declared a National Natural Landmark in December 1976.", "title": "" }, { "docid": "47137075", "text": "Swamp Meadow Bridge is a covered bridge crossing Hemlock Brook located on Central Pike in the town of Foster, Rhode Island. It is the second bridge to be built at this site.", "title": "" }, { "docid": "20087456", "text": "Big Bend Ranch State Park is a 311,000 acre state park located on the Rio Grande in Brewster and Presidio counties, Texas. It is the largest state park in Texas. The closest major town is Presidio, Texas, where the state park's head office is located.", "title": "" }, { "docid": "6732256", "text": "Big Lake State Park is a state park located in northwest Missouri, United States. The 407 acre park was established in 1932 at the northern end of the state's largest oxbow lake, Big Lake. Park activities include boating, camping, picnicking, fishing, and swimming.", "title": "" }, { "docid": "14842698", "text": "Georgesville is an unincorporated community in western Pleasant Township, Franklin County, Ohio, United States. It is located southwest of Columbus, the county seat of Franklin County and the capital and largest city of Ohio. Georgesville lies at the confluence of Little Darby Creek and Big Darby Creek, which are State and National Scenic Rivers and tributaries of the Scioto River. Much of the swamp forest and prairie surrounding Georgesville is part of Battelle Darby Creek Park.", "title": "" }, { "docid": "10794485", "text": "The Great Cypress Swamp (also known as \"Great Pocomoke Swamp\", \"Cypress Swamp\", or \"Big Cypress Swamp\"), is a forested freshwater swamp located on the Delmarva Peninsula in south Delaware and southeastern Maryland. As of 2000, it is the largest contiguous forest on the Delmarva Peninsula.", "title": "" }, { "docid": "38363779", "text": "Big Arm State Park is a Montana state park that is a unit of Flathead Lake State Park near Big Arm, Montana. Big Arm State Park is located on the western shores of Flathead Lake, the largest natural freshwater lake in the western United States. Recreational activities available in the park include fishing, boating, camping, swimming, and more. The campground has seven tent sites and 41 RV sites.", "title": "" }, { "docid": "3667546", "text": "Big Talbot Island State Park is a Florida State Park located on Big Talbot Island, 20 miles east of downtown Jacksonville on A1A North and immediately north of Little Talbot Island State Park.", "title": "" }, { "docid": "51125793", "text": "Big Deer State Park is a state park in Groton, Vermont. The park is a campground located in Groton State Forest close to the Groton Nature Center, Boulder Beach State Park and Stillwater State Park.", "title": "" }, { "docid": "3013169", "text": "Stephen Clark Foster (1820 – January 27, 1898) was a politician, the first American mayor of Los Angeles under United States military rule. Foster served in the state constitutional convention, and was elected to the State Senate. He was elected as mayor of Los Angeles in 1856, and later elected for four terms to the Los Angeles County Board of Supervisors.", "title": "" }, { "docid": "5383297", "text": "Parvin State Park, located in the southwestern part of New Jersey is a park whose history is as varied as its wildlife. Situated on the edge of the Pine Barrens, the park not only has pine forests, but also a swamp hardwood forest. The park is located near Pittsgrove Township in Salem County. The park is operated and maintained by the New Jersey Division of Parks and Forestry.", "title": "" }, { "docid": "43273814", "text": "Big Lake Cattle Mound is a historic earthen mound located in Congaree National Park near Hopkins, Richland County, South Carolina. It was built by settlers in the Congaree Swamp to provide a place of refuge for hogs, cattle, and other grazing animals during the flood season. The Big Lake Cattle Mount measures 75 feet long by 35 feet wide, with a 2 foot tall flat top.", "title": "" } ]
5a8c6088554299653c1aa053	Giuliani Time and A Life in the Death of Joe Meek are both films set in what genre of film making?	[ { "docid": "8937657", "text": "Giuliani Time is a 2005 documentary film by Kevin Keating about Rudy Giuliani, former Mayor of New York City.", "title": "" }, { "docid": "16195296", "text": "A Life in the Death of Joe Meek is an upcoming independent American documentary about the British record producer Joe Meek, made by Howard S. Berger and Susan Stahman. Slated to be released October 2017.", "title": "" } ]	[ { "docid": "12586991", "text": "Telstar: The Joe Meek Story is a 2008 film adaptation of James Hicks' and Nick Moran's play \"Telstar\", about record producer Joe Meek, which opened at the New Ambassadors Theatre in London’s West End in June 2005. The film is directed by Nick Moran and stars Con O'Neill, who also played Joe Meek in the original play, while Kevin Spacey plays Meek's business partner, Major Wilfred Banks.", "title": "" }, { "docid": "24924346", "text": "Carlo Giuliani, Boy (Italian: \"Carlo Giuliani, ragazzo\" ) is a 2002 Italian documentary film directed by Francesca Comencini. It was screened out of competition at the 2002 Cannes Film Festival. It details the death of Carlo Giuliani, who was shot dead by a police officer during the demonstrations against the Group of Eight in 2001.", "title": "" }, { "docid": "37964653", "text": "Gazzara is a 2012 film set in New York, based on the life and career of actor Ben Gazzara who writer/director Joseph Rezwin met in 1977 on the set of John Cassavetes’ \"Opening Night\". Their conversations about acting and art, fears and desires, life and death all culminate in the final Central Park sequence where Ben persuades Joe it is time to cut the cord, end the obsession with him and Cassavetes and pursue his passion of art and filmmaking in his own individual way as Ben did throughout his entire life.", "title": "" }, { "docid": "40497682", "text": "Shab-e Quzi (Persian: شب قوزی‎ ‎ ; literally Night of the Hunchback) is a 1965 Iranian film comedy film directed and produced by Farrokh Ghaffari. The film script was based on a story from One Thousand and One Nights, but arranged for modern city life in Tehran. This was Ghaffari's third film after \"Jonub-e Shahr\" (The South of the City) and \"Arous Kodumeh?\" (Which One is Bride) which both didn't have a good grossing. Jalal Moghaddam (another intellectual film director) and George Lichensky (an Iranian-Assyrian cinematographer) encouraged Ghaffari to make this film. At first the story was set in the medieval times as in the ancient stories of One Thousand and One Nights occurred. However, the censorship office forced Ghaffari to turn the story of the film to a modern setting.", "title": "" }, { "docid": "53014931", "text": "It's Not the Time of My Life (Hungarian: Ernelláék Farkaséknál ) is a 2016 Hungarian drama film directed by Szabolcs Hajdu. It is set in an apartment where two families interact and both couples go through a midlife crisis. The film is based on the director's own play.", "title": "" }, { "docid": "39587858", "text": "The Undertaker (also released as \"Death Merchant\") is a 1988 slasher film starring Joe Spinell and directed by Franco Steffanino. The film was completed in November 1988, but was never released for the public and existed only in an incomplete form. \"The Undertaker\" was later reedited for a DVD release by Code Red in 2010. The film is considered a cult classic, due in part to both Joe Spinell's involvement and its troubled production. This was Joe Spinell's last film before his premature death in 1989.", "title": "" }, { "docid": "50303927", "text": "Life Is What You Make It is a novel by Preeti Shenoy. The book was in “Top books of 2011” as per the Nielsen list which is published in \"Hindustan Times\". It was also on \"Times of India\" all-time best sellers of 2011. This is an astonishing love story set in India in 1990s. This is a book of love, hope and how determination can overcome even destiny.", "title": "" }, { "docid": "32142896", "text": "Comes A Bright Day is a British film. The film was written and directed by Simon Aboud, and stars Craig Roberts, Imogen Poots, Kevin McKidd and Timothy Spall. \"Comes A Bright Day\" is Aboud's directorial debut. The film is a mix of genres: a darkly comic thriller, involving a romance set within a heist, and a story about searching for the hidden gems that make life infinitely richer.", "title": "" }, { "docid": "2084367", "text": "Epic film is a style of filmmaking with large scale, sweeping scope, and spectacle. The usage of the term has shifted over time, sometimes designating a film genre and at other times simply synonymous with big budget filmmaking. Like epics in the classical literary sense it is often focused on a heroic character. An epic's ambitious nature helps to set it apart from other types of film such as the period piece or adventure film. Epic historical films would usually take a historical or a mythic event and add an extravagant setting and lavish costumes, accompanied by an expansive musical score with an ensemble cast, which would make them among the most expensive of films to produce. The most common subjects of epic films are royalty, and important figures from various periods in world history.", "title": "" }, { "docid": "10968468", "text": "This is a list of films set in Alaska, whether in part or in full. This North American setting is part of the Northern genre. It includes movies in which location shooting occurred both inside and outside of Alaska. Following the main list is a list of films which were filmed in Alaska, but set elsewhere.", "title": "" }, { "docid": "44121136", "text": "The Fabulous Joe is a 1947 American comedy film directed by Harve Foster and written by Arnold Belgard and Jack Jevne. The film stars Walter Abel, Margot Grahame, Marie Wilson, Donald Meek, Sheldon Leonard and Howard Petrie. The film was released on August 29, 1947, by United Artists.", "title": "" }, { "docid": "2888880", "text": "Life or Something Like It is a 2002 romantic comedy/drama film directed by Stephen Herek. The film focuses on television reporter Lanie Kerrigan (Angelina Jolie) and her quest to find meaning in her life. The original music score was composed by David Newman. The film's taglines are: \"Destiny is what you make of it\" and \"What if you had only 7 days to live?\"", "title": "" }, { "docid": "30539482", "text": "Mako: The Jaws of Death is a 1976 thriller film directed by William Grefe. The film is about a brooding loner who accidentally learns that he has a telepathic and emotional connection with sharks. He eventually rebukes society and sets out to protect sharks from people. The film was set and shot on location in Key West, Florida. This film is one of the first in the wave of films that sought to capitalize on the popularity of the 1975 feature film, \"Jaws\". \"Mako: The Jaws of Death\", with its sympathetic portrayal of sharks as the real \"victims\" of human exploitation, is notable in the maritime horror genre for having depicted the sharks as the heroes and man as the villain.", "title": "" }, { "docid": "11011632", "text": "The Nostril Picker is a 1993 horror film of the slasher genre. The film stars Carl Zschering as Joe Bukowski, a homicidal maniac who uses his special ability to get close to his female targets. Despite the name, the film plot does not directly revolve around a man who picks his nose. Instead, Joe Bukowski learns a chant from a homeless man in return for a small proportion of his alcoholic beverage, and this chant transforms Joe into a form of anybody he pleases. Joe is warned that when the chant is performed excessively it will make him crazy, but chooses to ignore this warning. His main victims in the film are teenage girls attending a high school close to his home. He takes the form of a girl and makes a 'friendship' with these girls but decides to murder, rape and eat them one by one.", "title": "" }, { "docid": "38394607", "text": "The survival film is a film genre in which one or more characters make an effort at physical survival. It often overlaps with other film genres. It is a subgenre of the adventure film, along with swashbuckler films, war films, and safari films. Survival films are darker than most other adventure films which usually focus their storyline on a single character, usually the protagonist. The films tend to be \"located primarily in a contemporary context\" so film audiences are familiar with the setting, meaning the characters' activities are less romanticized.", "title": "" }, { "docid": "9831946", "text": "\"Johnny Remember Me\" is a song which became a 1961 UK Single Chart #1 hit single for John Leyton, backed by The Outlaws. It was producer Joe Meek's first #1 production. Recounting the haunting – real or imagined – of a young man by his dead lover, the song is one of the most noted of the 'death ditties' that populated the pop charts, on both sides of the Atlantic, in the early to mid-1960s. It is distinguished in particular by its eerie, echoing sound (a hallmark of Meek's production style) and by the ghostly, foreboding female wails that form its backing vocal, by Lissa Gray. The recording was arranged by Charles Blackwell. The song was banned by the BBC, along with many other 'death discs', which were popular at the time.", "title": "" }, { "docid": "553272", "text": "A Matter of Life and Death is a 1946 British fantasy-romance film written, produced and directed by Michael Powell and Emeric Pressburger, and set in England during the Second World War. The film stars David Niven, Roger Livesey, Raymond Massey, Kim Hunter and Marius Goring.", "title": "" }, { "docid": "414565", "text": "Nick Adams (July 10, 1931February 7, 1968) was an American film and television actor and screenwriter. He was noted for his roles in several Hollywood films during the 1950s and 1960s along with his starring role in the ABC television series \"The Rebel\" (1959). Decades after Adams' death from a prescription drug overdose at the age of 36, his widely publicized friendships with James Dean and Elvis Presley would stir speculation about both his private life and the circumstances of his death. In an \"AllMovie\" synopsis for Adams' last film, reviewer Dan Pavlides wrote, \"Plagued by personal excesses, he will be remembered just as much for what he could have done in cinema as what he left behind.\"", "title": "" }, { "docid": "1272902", "text": "The British film-making partnership of Michael Powell (1905–1990) and Emeric Pressburger (1902–1988)—together often known as The Archers, the name of their production company—made a series of influential films in the 1940s and 1950s. —24 films between 1939 and 1972—were mainly derived from original stories by Pressburger with the script written by both Pressburger & Powell. Powell did most of the directing while Pressburger did most of the work of the producer and also assisted with the editing, especially the way the music was used. Unusually, the pair shared a writer-director-producer credit for most of their films. The best known of these are \"The Life and Death of Colonel Blimp\" (1943), \"A Canterbury Tale\" (1944), \"A Matter of Life and Death\" (1946), \"Black Narcissus\" (1947), \"The Red Shoes\" (1948), and \"The Tales of Hoffmann\" (1951).", "title": "" }, { "docid": "40634820", "text": "The Life and Death of a Porno Gang (Serbian: \"Život i smrt porno bande\") is a 2009 Serbian horror film following a group of travelling sex show performers and pornographic filmmakers who are lured into making snuff films.", "title": "" }, { "docid": "1176486", "text": "A mondo film (from the Italian word for \"world\") is an exploitation documentary film, sometimes resembling a pseudo-documentary and usually depicting sensational topics, scenes, or situations. Common traits of mondo films include an emphasis on taboo subjects (such as death and sex), portrayals of foreign cultures (which have drawn accusations of ethnocentrism or racism), and staged sequences presented as genuine documentary footage. Over time, the films placed increasing emphasis on footage of the dead and dying (both real and fake). The term shockumentary is also used to describe the genre.", "title": "" }, { "docid": "25440", "text": "Robert Joseph Flaherty, FRGS ( ; February 16, 1884 – July 23, 1951) was an American filmmaker who directed and produced the first commercially successful feature-length documentary film, \"Nanook of the North\" (1922). The film made his reputation and nothing in his later life fully equaled its success, although he continued the development of this new genre of narrative documentary, e.g. with \"Moana\" (1926), set in the South Seas, and \"Man of Aran\" (1934), filmed in Ireland's Aran Islands. He is considered the \"father\" of both the documentary and the ethnographic film.", "title": "" }, { "docid": "7293095", "text": "\"You Light Up My Life\" is a ballad written by Joseph \"Joe\" Brooks, and originally recorded by Kasey Cisyk for the soundtrack album to the 1977 film of the same name. The song was lip synched in the film by its lead actress, Didi Conn. The best-known version of the song is a cover by Debby Boone, the daughter of singer Pat Boone, which held the #1 position on the \"Billboard\" Hot 100 chart for ten consecutive weeks in 1977, setting a new record for that time.", "title": "" }, { "docid": "37708077", "text": "What Richard Did is a 2012 Irish film directed by Lenny Abrahamson and written by Malcolm Campbell. The film is loosely based on Kevin Power's \"Bad Day in Blackrock\", a fictionalised novel inspired by the real-life death of Brian Murphy in 2000. It won the best Irish film of the year award at the 10th Irish Film & Television Awards and was the most commercially successful Irish film of 2012.", "title": "" }, { "docid": "11038839", "text": "Open Doors (Italian: Porte aperte ) is a 1990 Italian film directed by Gianni Amelio. Set in Palermo in the 1930s, a judge who is morally against the death penalty is confronted with the case of a man who has murdered his wife and two colleagues in cold blood. Opposed by both the fascist government and public opinion, he struggles to do what he believes is right. Based on a 1968 novel, \"Porte Aperte\", by Leonardo Sciascia. The film was selected as the Italian entry for the Best Foreign Language Film at the 63rd Academy Awards.", "title": "" }, { "docid": "23319745", "text": "Splatter: Love, Honor and Paintball is a 2010 comedy film written and directed by Lonnie Schuyler, produced by Bruce Heppner-Elgin, filmed in Burlington and Washington, Iowa. The film had a $6 million budget and has about 100 cast and crew members; it stars Matt Geiler and Kim Kurtenbach Furness. Early press releases describe the film as “the story of a likable loser who finally realizes what makes life worthwhile and sets out to win back the love of his ex-wife and the respect of his son - in a paintball tournament!”", "title": "" }, { "docid": "46427022", "text": "Amy is a 2015 British documentary film about the life and death of British singer-songwriter Amy Winehouse. Directed by Asif Kapadia and produced by James Gay-Rees, George Pank, and Paul Bell and co-produced by Krishwerkz Entertainment, On The Corner Films, Playmaker Films, and Universal Music, in association with Film 4. The film covers Winehouse's life and her struggle with substance abuse, both before and after her career blossomed, and which eventually caused her death.", "title": "" }, { "docid": "3345117", "text": "Uta Erickson (who often used the stage names \"Artemidia Grillet\" and \"Carla Erikson\") was a Norwegian actress who was in many sexploitation films of the late 1960s. She starred in several provocatively titled films directed by Michael and Roberta Findlay, including \"The Kiss Of Her Flesh\", \"A Thousand Pleasures\", \"The Curse Of Her Flesh\", and \"The Ultimate Degenerate\". Erickson was also a favorite of directors Doris Wishman (\"Love Toy\") and Barry Mahon (\"Sex Killer\"). Some of her films, notably \"Mnasidika\" were arty enough to pass as the \"low end\" of an arthouse pairing with a film by a European auteur. At her best, such as in \"Passion in Hot Hollows \" directed by Joe Sarno, her acting could make a softcore scene far more erotic. \"Deep Throat\" rang the death knell to this softcore genre and effectively ended Erickson's film career.", "title": "" }, { "docid": "42053", "text": "The spy film genre deals with the subject of fictional espionage, either in a realistic way (such as the adaptations of John le Carré) or as a basis for fantasy (such as many James Bond films). Many novels in the spy fiction genre have been adapted as films, including works by John Buchan, le Carré, Ian Fleming (Bond) and Len Deighton. It is a significant aspect of British cinema, with leading British directors such as Alfred Hitchcock and Carol Reed making notable contributions and many films set in the British Secret Service.", "title": "" }, { "docid": "22462670", "text": "BookWars is an award-winning independent film from New York City by Jason \"Jack RO\" Rosette produced by Camerado, about the life and times of New York City street booksellers. Made on an ultra-low budget in a jazzy, impressionistic style reminiscent of the films of Robert Frank and poetry of the Beat Generation, \"BookWars\" is the only first-person documentary made during then-New York City Mayor Rudolph Giuliani's controversial \"Quality of Life\" campaign, which sought to limit and control individuals engaged in informal economic activities on the streets of New York City.", "title": "" } ]
3492	If a startup can always issue new shares, what value is there to stocks/options?	[ { "docid": "267266", "text": "\"It's called \"\"dilution\"\". Usually it is done to attract more investors, and yes - the existing share holders will get diluted and their share of ownership shrinks. As a shareholder you can affect the board decisions (depends on your stake of ownership), but usually you'll want to attract more investors to keep the company running, so not much you can do to avoid it. The initial investors/employees in a startup company are almost always diluted out. Look at what happened to Steve Jobs at Apple, as an example.\"", "title": "" }, { "docid": "285041", "text": "\"Companies normally do not give you X% of shares, but in effect give you a fixed \"\"N\"\" number of shares. The \"\"N\"\" may translate initially to X%, but this can go down. If say we began with 100 shares, A holding 50 shares and B holding 50 shares. As the startup grows, there is need for more money. Create 50 more shares and sell it at an arranged price to investor C. Now the percentage of each investor is 33.33%. The money that comes in will go to the company and not to A & B. From here on, A & C together can decide to slowly cut out B by, for example: After any of the above the % of shares held by B would definitely go down.\"", "title": "" }, { "docid": "154841", "text": "The short answer, probably not much. Unless you have a controlling interest in the company. If at least 50%+1 of the shareholder votes are in favor of the dilution then it can be done. There are some SEC rules that should protect against corporate looting and theft like what the Severin side is trying to make it appear as happened. However it would appear that Severin did something stupid. He signed away all of his voting right to someone who would use them to make his rights basically worthless. Had he kept his head in the game he could probably have saved himself. But he didn't. If your average startup started issuing lots of stock and devaluing existing shares significantly then I would expect it would be harder to find investors willing to watch as their investment dwindled. But if you are issuing a limited amount stock to get leverage to grow bigger then it is worth it. In the .com bubble there were quite a few companies that just issued stock to buy other companies. Eventually most of these companies got delisted because they diluted them selves to much when they were overvalued. Any company not just a startup can dilute its shares. Many if not most major companies issue stock to raise capital. This capital is then generally used to build the business further and increase the value of all shares. Most of the time this dilution is very minor (<.1%) and has little if any impact on the stock. There are rules that have to be followed as listed companies are regulated by the SEC. There are less regulations with private corporations. It looks like the dilution was combined with the buyout of the Florida company which probably contributed to the legality of the dilution. With options they are generally issued at a set price. This may be higher or lower than the reported sell price of the stock when the option is issued. The idea is over time the stock will increase in value so that those people who hold on to their options can buy the stock for the price listed on the option. I worked at an ISP start up in the 90's that made it pretty well. I left before the options were issued but I had friends still there that were issued an option at $16 a share the value of the stock at the time of the issue of the option was about 12. Well the company diluted the shares and used them to acquire more ISP's unfortunately this was about the time that DSL And cable internet took off so the dial up market tanked. The value eventually fell to .10 they did a reverse split and when they did the called in all options. The options did not have a positive cash value at any time. Had RMI ever made it big then the options could have been worth millions. There are some people from MS and Yahoo that were in early that made millions off of their options. This became a popular way for startups to attract great talent paying peanuts. They invested their time in the business hoping to strike gold. A lot of IT people got burned so this is less popular among top talent as the primary compensation anymore.", "title": "" } ]	[ { "docid": "480119", "text": "As a start-up, the initial shares can be given at various price points. So essentially they can give someone a larger percentage based on the same amount earlier, and lesser percentage to someone else for the same amount. As its a start-up the valuations can be very tricy and what matters is that whether you believe the percentage you got for the amount is right or not. It is very important to note that when you have been given an ownership in the company, how that is designated. Is it in absolute number of shares or is it in terms of percentage based on the existing shares. For example you maybe given 100 shares, without any qualification. Or you maybe given a 5% stake in the paid-up capital, that translates to 100 shares. It is always better to hold the shares in % of the total shares. Also read the contract, any dilution should require your approval. Normally start-ups once the valuation starts to go up, start creating more shares and sell these to private equity or create more shares and give it as a bonus to promoters. Hence in both cases your holding will keep getting diluted. There is a related quesiton If a startup can always issue new shares, what value is there to stocks/options?", "title": "" }, { "docid": "277305", "text": "Hah, good luck getting those kind of terms. There's always another fresh-faced new grad with dollar signs in his eyes who doesn't know enough to ask about outstanding shares, dilution, or preferences. Very few startups are looking for penny-ante 'investor' employees who can only put <$100k. That's what co-founders are for. Actual employees are lucky if they can properly value their options, let alone control how much it ends up being worth in the end.", "title": "" }, { "docid": "592619", "text": "> There's always another fresh-faced new grad with dollar signs in his eyes who doesn't know enough to ask about outstanding shares, dilution, or preferences. They'll learn soon enough. > Very few startups are looking for penny-ante 'investor' employees who can only put <$100k. You'll probably find that the majority of tech startups are looking for under $100k to get going. Check out kickstarter.com sometime. > Actual employees are lucky if they can properly value their options, let alone control how much it ends up being worth in the end. If you're asked to put in work without being fully compensated, you are no longer an employee. You're an investor. You need to change your way of thinking.", "title": "" }, { "docid": "534870", "text": "Why do companies exist? Well, the corporate charter describes why the company exists. Usually the purpose is to enrich the shareholders. The owners of a company want to make money, in other words. There are a number of ways that a shareholder can make money off a stock: As such, maintaining the stock price and dividend payouts are generally the number one concern for any company in the long term. Most of the company's business is going to be directed towards making the company more valuable for a future buyout, or more valuable in terms of what it can pay its shareholders directly. Note that the company doesn't always need to be worried about the specifics of the day-to-day moves of the stock. If it keeps the finances in line - solid profits, margins, earnings growth and the like - and can credibly tell people that it's generally a valuable business, it can usually shrug off any medium-term blips as market craziness. Some companies are more explicitly long-term about things than others (e.g. Berkshire Hathaway basically tells people that it doesn't care all that much about what happens in the short term). Of course, companies are abstractions, and they're run by people. To make the people running the company worry about the stock price, you give them stock. Or stock options, or something like that. A major executive at a big company is likely to have a significant amount of stock. If the company does well, he does well; if it does poorly, he does poorly. Despite a few limitations, this is really a powerful incentive. If a company is losing a lot of money, or if its profits are falling so it's just losing a lot of its value as a business, the owners (stockholders) tend to get upset, and may vote in new management, or launch some sort of shareholder lawsuit. And, as previously noted, to raise funds, a company can also issue new shares to the market as a secondary offering as well (and they can issue fewer shares if the price is high - meaning that whatever the company is worth afterward, the existing owners own proportionally more of it).", "title": "" }, { "docid": "525590", "text": "As others have posted, the company gains capital in return for its new shares. However, the share price can still fall. The problem is that the share marked is affected by supply and demand like any other marked. If the company just issues the new shares at marked price, they will have problems finding buyers. The people who are willing to pay that price has already bought as many shares as they want. The company does this to raise capital, and depends on the shares actually selling for this to work. So, they issue shares at below marked price to attract buyers and the shares get diluted. In the end the share will usually end up somewhere between the old marked price and the issue price. The old share owners are probably not too happy about this and will not accept this plan. (At least here in Norway, share issue has to be accepted at a shareholder meeting) So, what is often done instead is to issue buy options for the required number of shares at the below-marked price. These options are given (for free) to the current share holders proportional to their current holding. If everybody exercises their options they get new cheap shares that compensates for the loss of share value. If they don't have the capital themselves, they can sell the options and get compensation that way instead.", "title": "" }, { "docid": "427726", "text": "While on the surface it may seem that the warrant you described is trading below intrinsic value, there are many reasons why that might not be the case. It's more likely that you are lacking information, than having identified a derivative instrument that the market has failed to reasonably price. For instance, might there be a conversion ratio on the warrants other than the 1:1 ratio that you seem to be assuming? Sometimes, warrant terms are such that multiple warrants are required to buy one share of stock. Consider: The conversion ratio is the number of warrants needed in order to buy (or sell) one investment unit. Therefore, if the conversion ratio to buy stock XYZ is 3:1, this means that the holder needs three warrants in order to purchase one share. Usually, if the conversion ratio is high, the price of the share will be low, and vice versa. (source) Conversion ratios are sometimes used so that warrants can be issued on a 1:1 basis to existing stockholders, but where the potential number of new shares to be issued is much less. Conversion ratio is just one such example that could lead to perceived mispricing, and there may be other restrictions on exercise. Warrants are not issued by an options exchange using standardized option contract terms, and so warrant terms vary considerably from issuer to issuer. Even series of warrants from the same issuer may have differing terms. Always look beyond any warrant quote to find a definitive source of the warrant's precise terms — and read those terms carefully before taking any position.", "title": "" }, { "docid": "551893", "text": "A stock is an ownership interest in a company. There can be multiple classes of shares, but to simplify, assuming only one class of shares, a company issues some number of shares, let's say 1,000,000 shares and you can buy shares of the company. If you own 1,000 shares in this example, you would own one one-thousandth of the company. Public companies have their shares traded on the open market and the price varies as demand for the stock comes and goes relative to people willing to sell their shares. You typically buy stock in a company because you believe the company is going to prosper into the future and thus the value of its stock should rise in the open market. A bond is an indebted interest in a company. A company issues bonds to borrow money at an interest rate specified in the bond issuance and makes periodic payments of principal and interest. You buy bonds in a company to lend the company money at an interest rate specified in the bond because you believe the company will be able to repay the debt per the terms of the bond. The value of a bond as traded on the open exchange varies as the prevailing interest rates vary. If you buy a bond for $1,000 yielding 5% interest and interest rates go up to 10%, the value of your bond in the open market goes down so that the payment terms of 5% on $1,000 matches hypothetical terms of 10% on a lesser principal amount. Whatever lesser principal amount at the new rate would lead to the same payment terms determines the new market value. Alternatively, if interest rates go down, the current value of your bond increases on the open market to make it appear as if it is yielding a lower rate. Regardless of the market value, the company continues to pay interest on the original debt per its terms, so you can always hold onto a bond and get the original promised interest as long as the company does not go bankrupt. So in summary, bonds tend to be a safer investment that offers less potential return. However, this is not always the case, since if interest rates skyrocket, your bond's value will plummet, although you could just hold onto them and get the low rate originally promised.", "title": "" }, { "docid": "427145", "text": "In Australia there are 2 type of warrants (I don't know if it is the same in the US, UK and other countries), the first are trading warrants and the second are instalment warrants. The trading warrants are exactly what it says, they are used for trading. They are similar to option and have calls and puts. As Cameron says, they differ from exchange traded options in that they are issued by the financial companies whereas options are generally written by other investors. Instalment warrants on the other hand are usually bought and sold by investors with a longer term view. There are no calls and puts and you can just go long with them. They are also issued by financial companies, and how they work is best explained through an example: if I was to buy a stock directly say I would be paying $50 per share, however an instalment warrant in the underlying stock may be offered for $27 per warrant. I could buy the warrant directly from the company when it is issued or on the secondary market just like shares. I would pay the $27 per warrant upfront, and then in 2 years time when the warrant expires I have the choice to purchase the underlying stock for the strike price of say $28, roll over to a new issue of warrants, sell it back on the secondary market, or let it expire, in which case I would receive any intrinsic value left in the warrant. You would have noticed that the warrant purchase price plus the strike price adds up to more than the share price ($55 compared to $50). This is the interest component inherent in the warrant which covers the borrowing costs until expiry, when you pay the second portion (the strike price) and receive the underlying shares. Another difference between Instalment warrants and trading warrants (and options) is that with instalment warrants you still get the full dividends just like the shares, but at a higher yield than the shares.", "title": "" }, { "docid": "467081", "text": "\"Different stocks balance dividend versus growth differently. Some have relatively flat value but pay a strong dividend -- utility stocks used to be examples of that model, and bonds are in some sense an extreme version of this. Some, especially startups, pay virtually no dividends and aim for growth in the value of the stock. And you can probably find a stock that hits any point between these. This is the \"\"growth versus income\"\" spectrum you may have heard mentioned. In the past, investors took more of their return on investment as dividends -- conceptually, a share of the company's net profits for the year reflecting the share's status as partial ownership. If you wanted to do so, you could use the dividend to purchase more shares (via a dividend reinvestment plan or not), but that was up to you. These days, with growth having been strongly hyped, many companies have shifted much more to the growth model and dividends are often relatively wimpy. Essentially, this assumes that everyone wants the money reinvested and will take their profit by having that increase the value of their shares. Of course that's partly because some percentage of stockholders have been demanding growth at all costs, not always realistically. To address your specific case: No, you probably aren't buying Microsoft because you like its dividend rate; you're buying it in the hope it continues to grow in stock value. But the dividend is a bit of additional return on your investment. And with other companies the tradeoff will be different. That's one of the things, along with how much you believe in the company, that would affect your decision when buying shares in specific companies. (Personally I mostly ignore the whole issue, since I'm in index funds rather than individual stocks. Picking the fund sets my overall preference in terms of growth versus income; after that it's their problem to maintain that balance.)\"", "title": "" }, { "docid": "5846", "text": "\"I think JB King's answer is interesting from the point of view of \"\"is this good for me\"\" but the OP's question boils down to \"\"why would a company do this?\"\" The company buys back shares when it thinks it will better position the company financially. A Simple Scenario: If Company A wants to open a new store, for example, they need to buy the land, build the store, stock it, etc, etc and this all costs money. The company can get a loan, use accrued capital, or raise new capital by issuing new stock. Each method has benefits and drawbacks. One of the drawbacks of issuing new stock is that it dilutes the existing stock's value. Previously, total company profits were split between x shares. Now the profits are shared between x+y shares, where y is the number of new shares issued to raise the capital. This normally drives the price of the stock down, since the expected future dividends per stock have decreased. Now the company has a problem: the next time they go to raise money by issuing stock, they will have to issue MORE shares to get the same value - leading to more dilution. To break out of this cycle, the company can buy back shares periodically. When the company feels the the stock is sufficiently undervalued, it buys some back. Now the profits are shared with a smaller pool, and the stock price goes up, and the next time Company A needs to raise capital, it can issue stock. So it probably has little to do with rewarding shareholders, and more to do with lowering the \"\"cost of capital\"\" for the company in the future.\"", "title": "" }, { "docid": "135216", "text": "\"The market capitalization of a stock is the number of shares outstanding (of each stock class), times the price of last trade (of each stock class). In a liquid market (where there are lots of buyers and sellers at all price points), this represents the price that is between what people are bidding for the stock and what people are asking for the stock. If you offer any small amount more than the last price, there will be a seller, and if you ask any small amount less than the last price, there will be a buyer, at least for a small amount of stock. Thus, in a liquid market, everyone who owns the stock doesn't want to sell at least some of their stock for a bit less than the last trade price, and everyone who doesn't have the stock doesn't want to buy some of the stock for a bit more than the last trade price. With those assumptions, and a low-friction trading environment, we can say that the last trade value is a good midpoint of what people think one share is worth. If we then multiply it by the number of shares, we get an approximation of what the company is worth. In no way, shape or form does it not mean that there is 32 billion more invested in the company, or even used to purchase stock. There are situations where a 32 billion market cap swing could mean 32 billion more money was invested in the company: the company issues a pile of new shares, and takes in the resulting money. People are completely neutral about this gathering in of cash in exchange for dilluting shares. So the share price remains unchanged, the company gains 32 billion dollars, and there are now more shares outstanding. Now, in some sense, there is zero dollars currently invested in a stock; when you buy a stock, you no longer have the money, and the money goes to the person who no longer has the stock. The issue here is the use of the continuous tense of \"\"invested in\"\"; the investment was made at some point, but the money doesn't really stay in this continuous state of being. Unless you consider the investment liquid, and the option to take money out being implicit, it being a continuous action doesn't make much sense. Sometimes the money is invested in the company, when the company causes stocks to come into being and sells them. The owners of stocks has invested money in stocks in that they spent that money to buy the stocks, but the total sum of money ever spent on stocks for a given company is not really a useful value. The market capitalization is an approximation, which under the efficient market hypothesis (that markets find the correct price for things nearly instantly) is reasonably accurate, of the value the company has collectively to its shareholders. The efficient market hypothesis isn't accurate, but it is an acceptable rule of thumb. Now, this value -- market capitalization -- is arguably not the total value of a company: other stakeholders include bond holders, labour, management, various contract counter-parties, government and customers. Some companies are structured so that almost all value is captured not by the stock owners, but by contract counter-parties (this is sometimes used for hiding assets or debts). But for most large publically traded companies, it (in theory) shouldn't be far off.\"", "title": "" }, { "docid": "93215", "text": "\"Typically, there are three ways an acquisition is financed. What is used is called the \"\"consideration\"\". 1.) Cash - Existing cash on the balance sheet is used. Think of it like purchasing something with your debit card. 2.) Stock - This a bit more complicated. The acquiring company issues new shares and exchanges those shares for shares of the acquiree. Because new shares are issued, this can have a dilutive effect on the stock price of the acquirer. However, it can have an accretive effect if enough synergistic value between the two companies is realized and/or expected. 3.) Debt - Basically like taking out a loan. The \"\"consideration\"\" for a deal is often reported, as you read in your article. Most deals are a combination of cash/stock/debt. (Debt is often referred to as \"\"cash\"\" - i.e. if you take out a loan, you are essentially receiving cash.) When it comes to which is best to use, there are quantitative analyses for that - with a specific focus on the acquirer's EPS (Earnings per share) post-deal. The factors that are considered are the forgone interest on cash, the additional interest gained from taking on debt, and the dilutive effects of issuing new stock. There is no right answer for which is best, as there are multiple different factors and circumstances involved across M&A deals. Each company has different borrowing rates and synergistic value expected from their deals. One big factor is the timing and stock price of both companies during the deal. If the acquirer is trading at an all time high and the acquiree is at an all time low, then perhaps an all-stock deal would be advantageous to the buyer. Typically, companies want to avoid stock deals because they are the most dilutive.\"", "title": "" }, { "docid": "261522", "text": "Like others have already said, it may cause an immediate dip due to a large and sudden move in shares for that particular stock. However, if there is nothing else affecting the company's financials and investors perceive no other risks, it will probably bounce back a bit, but not back to the full value before the shares were issued. Why? Whenever a company issues more stock, the new shares dilute the value of the current shares outstanding, simply because there are now more shares of that stock trading on the market; the Earnings Per Share (EPS) Ratio will drop since the same profit and company value has to be spread across more shares. Example: If a company is valued at $100 dollars and they have 25 shares outstanding, then the EPS ratio equates to $4 per share (100/25 = 4). If the company then issues more shares (stock to employees who sell or keep them), let's say 25 more shares, then shares outstanding increase to 50, but the company's value still remains at $100 dollars. EPS now equates to $2 per share (100/50 = 2). Now, sometimes when shareholders (especially employees...and especially employees who just received them) suddenly all sell their shares, this causes a micro-panic in the market because investors believe the employees know something bad about the company that they don't. Other common shareholders then want to dump their holdings for fear of impending collapse in the company. This could cause the share price to dip a bit below the new diluted value, but again if no real, immediate risks exist, the price should go back up to the new, diluted value. Example 2: If EPS was at $4 before issuing more stock, and then dropped to $2 after issuing new stock, the micro-panic may cause the EPS to drop below $2 and then soon rebound back to $2 or more when investors realize no actual risk exists. After the dilution phase plays out, the EPS could actually even go above the pre-issuing value of $4 because investors may believe that since more stock was issued due to good profits, more profits may ensue. Hope that helps!", "title": "" }, { "docid": "22207", "text": "\"I agree with all the people cautioning against working for free, but I'll also have a go at answering the question: When do I see money related to that 5%? Is it only when they get bought, or is there some sort of quarterly payout of profits? It's up to the shareholders of the company whether and when it pays dividends. A new startup will typically have a small number of people, perhaps 1-3, who between them control any shareholder vote (the founder(s) and an investor). If they're offering you 5%, chances are they've made sure your vote will not matter, but some companies (an equity partnership springs to mind) might be structured such that control is genuinely distributed. You would want to check what the particular situation is in this company. Assuming the founders/main investors have control, those people (or that person) will decide whether to pay dividends, so you can ask them their plans to realise money from the company. It is very rare for startups to pay any dividends. This is firstly because they're rarely profitable, but even when they are profitable the whole point of a startup is to grow, so there are plenty of things to spend cash on other than payouts to shareholders. Paying anything out to shareholders is the opposite of receiving investment. So unless you're in the very unusual position of a startup that will quickly make so much money that it doesn't need investment, and is planning to pay out to shareholders rather than spend on growth, then no, it will not pay out. One way for a shareholder to exit is to be bought out by other shareholders. For example if they want to get rid of you then they might make you an offer for your 5%. This can be any amount they think you'll take, given the situation at the time. If you don't take it, there may be things they can do in future to reduce its value to you (see below). If you do take it then your 5% would pay you once, when you leave. If the company succeeds, commonly it will be wholly or partly sold (either privately or by IPO). At this point, if it's wholly sold then the soon-to-be-ex-shareholders at the time will receive the proceeds of the sale. If it's partly sold then as with an investment round it's up for negotiation what happens. For example I believe the cash from an IPO of X% of the company could be taken into the company, leaving the shareholders with no immediate direct payout but (100-X)% of shares in their names that they're more-or-less free to sell, or retain and receive future dividends. Alternatively, if the company settles down as a small private business that's no longer in startup mode, it might start paying out without a sale. If the company fails, as most startups do, it will never pay anything. It's very important to remember that it's the shareholders at the time who receive money in proportion to their holding (or as defined by the company articles, if there are different classes of share). Just because you have 5% now doesn't mean you'll have 5% by that time, because any new investment into the company in the mean time will \"\"dilute\"\" your shareholding. It works like this: Note that I've assumed for simplicity that the new investment comes in at equal value to the old investment. This isn't necessarily the case, it can be more or less according to the terms of the new investment voted for by the shareholders, so the first line really is \"\"nominal value\"\", not necessarily the actual cash the founders put in. Therefore, you should not think of your 5% as 5% of what you imagine a company like yours might eventually exit for. At best, think of it as 5% of what a company like yours might exit for, if it receives no further investment whatsoever. Ah, but won't the founders also have their holdings diluted and lose control of the company, so they wouldn't do that? Well, not necessarily. Look carefully at whether you're being offered the same class of shares as the founders. If not consider whether they can dilute your shares without diluting their own. Look also at whether a new investor could use the founders' executive positions to give them new equity in the same way they gave you old equity, without giving you any new equity. Look at whether the founders will themselves participate in future investment rounds using sacks of cash that they own from other ventures, when you can't afford to keep up. Look at whether new investors will receive a priority class of share that's guaranteed at exit to pay out a certain multiple of the money invested before the older, inferior classes of shares receive anything (VCs like to do this, at least in the UK). Look at any other tricks they can legally pull: even if the founders aren't inclined to be tricky, they may eventually be forced to consider pulling them by a future new investor. And when I say \"\"look\"\", I mean get your lawyer to look. If your shareholding survives until exit, then it will pay out at exit. But repeated dilutions and investors with priority classes of shares could mean that your holding doesn't survive to exit even if the company does. Your 5% could turn into a nominal holding that hasn't really \"\"survived\"\", that entitles you to 0.5% of any sale value over $100 million. Then if the company sells for $50 million you get $0, while other investors are getting a good return. All of this is why you should not work for equity unless you can afford to work for free. And even then you need to lawyer up, now and during any future investment, so your lawyer can explain to you what your investment actually is, which almost certainly is different from what it looks like at a casual uninformed glance.\"", "title": "" }, { "docid": "453582", "text": "\"Investopedia explains how a stock split impacts the stock's options: Each option contract is typically in control of 100 shares of an underlying security at a predetermined strike price. To find the new coverage of the option, take the split ratio and multiply by the old coverage (normally 100 shares). To find the new strike price, take the old strike price and divide by the split ratio. Say, for example, you own a call for 100 shares of XYZ with a strike price of $75. Now, if XYZ had a stock split of 2 for 1, then the option would now be for 200 shares with a strike price of $37.50. If, on the other hand, the stock split was 3 for 2, then the option would be for 150 shares with a strike price of $50. So, yes, a 2 for 1 stock split would halve the option strike prices. Also, in case the Investopedia article isn't clear, after a split the options still control 100 shares per contract. Regarding how a dividend affects option prices, I found an article with a good explanation: As mentioned above, dividends payment could reduce the price of a stock due to reduction of the company's assets. It becomes intuitive to know that if a stock is expected to go down, its call options will drop in extrinsic value while its put options will gain in extrinsic value before it happens. Indeed, dividends deflate the extrinsic value of call options and inflate the extrinsic value of put options weeks or even months before an expected dividend payment. Extrinsic value of Call Options are deflated due to dividends not only because of an expected reduction in the price of the stock but also due to the fact that call options buyers do not get paid the dividends that the stock buyers do. This makes call options of dividend paying stocks less attractive to own than the stocks itself, thereby depressing its extrinsic value. How much the value of call options drop due to dividends is really a function of its moneyness. In the money call options with high delta would be expected to drop the most on ex-date while out of the money call options with lower delta would be least affected. If a stock is expected to drop by a certain amount, that drop would already have been priced into the extrinsic value of its put options way beforehand. This is what happens to put options of dividend paying stocks. This effect is again a function of options moneyness but this time, in the money put options raise in extrinsic value more than out of the money put options. This is because in the money put options with delta of close to -1 would gain almost dollar or dollar on the drop of a stock. As such, in the money put options would rise in extrinsic value almost as much as the dividend rate itself while out of the money put options may not experience any changes since the dividend effect may not be strong enough to bring the stock down to take those out of the money put options in the money. So, no, a dividend of $1 will not necessarily decrease an option's price by $1 on the ex-dividend date. It depends on whether it's a call or put option, and whether the option is \"\"in the money\"\" or \"\"out of the money\"\" and by how much.\"", "title": "" }, { "docid": "418150", "text": "If a stock that makes up a big part of the Dow Jones Industrial Average decided to issue a huge number of additional shares, that will make the index go up. At least this is what should happen, since an index is basically a sum of the market cap of the contributing companies. No, indices can have various weightings. The DJIA is a price-weighted index not market-cap weighted. An alternative weighting besides market-cap and price is equal weighting. From Dow Jones: Dow Jones Industrial Average™. Introduced in May 1896, the index, also referred to as The Dow®, is a price-weighted measure of 30 U.S. blue-chip companies. Thus, I can wonder what in the new shares makes the index go up? If a stock is split, the Dow divisor is adjusted as one could easily see how the current Dow value isn't equal to the sum or the share prices of the members of the index. In other cases, there may be a dilution of earnings but that doesn't necessarily affect the stock price directly as there may be options exercised or secondary offerings made. SO if the index, goes up, will the ETF DIA also go up automatically although no additional buying has happened in the ETF itself? If the index rises and the ETF doesn't proportionally, then there is an arbitrage opportunity for someone to buy the DIA shares that can be redeemed for the underlying stocks that are worth more in this case. Look at the Creation and Redemption Unit process that exists for ETFs.", "title": "" }, { "docid": "427859", "text": "\"I think it's easiest to illustrate it with an example... if you've already read any of the definitions out there, then you know what it means, but just don't understand what it means. So, we have an ice cream shop. We started it as partners, and now you and I each own 50% of the company. It's doing so well that we decide to take it public. That means that we will be giving up some of our ownership in return for a chance to own a smaller portion of a bigger thing. With the money that we raise from selling stocks, we're going to open up two more stores. So, without getting into too much of the nitty gritty accounting that would turn this into a valuation question, let's say we are going to put 30% of the company up for sale with these stocks, leaving you and me with 35% each. We file with the SEC saying we're splitting up the company ownership with 100,000 shares, and so you and I each have 35,000 shares and we sell 30,000 to investors. Then, and this depends on the state in the US where you're registering your publicly traded corporation, those shares must be assigned a par value that a shareholder can redeem the shares at. Many corporations will use $1 or 10 cents or something nominal. And we go and find investors who will actually pay us $5 per share for our ice cream shop business. We receive $150,000 in new capital. But when we record that in our accounting, $5 in total capital per share was contributed by investors to the business and is recorded as shareholder's equity. $1 per share (totalling $30,000) goes towards actual shares outstanding, and $4 per share (totalling $120,000) goes towards capital surplus. These amounts will not change unless we issue new stocks. The share prices on the open market can fluctuate, but we rarely would adjust these. Edit: I couldn't see the table before. DumbCoder has already pointed out the equation Capital Surplus = [(Stock Par Value) + (Premium Per Share)] * (Number of Shares) Based on my example, it's easy to deduce what happened in the case you've given in the table. In 2009 your company XYZ had outstanding Common Stock issued for $4,652. That's probably (a) in thousands, and (b) at a par value of $1 per share. On those assumptions we can say that the company has 4,652,000 shares outstanding for Year End 2009. Then, if we guess that's the outstanding shares, we can also calculate the implicit average premium per share: 90,946,000 ÷ 4,652,000 == $19.52. Note that this is the average premium per share, because we don't know when the different stocks were issued at, and it may be that the premiums that investors paid were different. Frankly, we don't care. So clearly since \"\"Common Stock\"\" in 2010 is up to $9,303 it means that the company released more stock. Someone else can chime in on whether that means it was specifically a stock split or some other mechanism... it doesn't matter. For understanding this you just need to know that the company put more stock into the marketplace... 9,303 - 4,652 == 4,651(,000) more shares to be exact. With the mechanics of rounding to the thousands, I would guess this was a stock split. Now. What you can also see is that the Capital Surplus also increased. 232,801 - 90,946 == 141,855. The 4,651,000 shares were issued into the market at an average premium of 141,855 ÷ 4,651 == $30.50. So investors probably paid (or were given by the company) an average of $31.50 at this split. Then, in 2011 the company had another small adjustment to its shares outstanding. (The Common Stock went up). And there was a corresponding increase in its Capital Surplus. Without details around the actual stock volumes, it's hard to get more exact. You're also only giving us a portion of the Balance Sheet for your company, so it's hard to go into too much more detail. Hopefully this answers your question though.\"", "title": "" }, { "docid": "178497", "text": "Stock options represent an option to buy a share at a given price. What you have been offered is the option to buy the company share at a given price ($5) starting a given date (your golden handcuffs aka vesting schedule). If the company's value doubles in 1 year and the shares are liquid (i.e. you can sell them) then you've just made $125k of profit. If the company's value has gone to zero in 1 year then you've lost nothing other than your hopes of getting rich. As others have mentioned, the mechanics of exercising the option and selling the shares can typically be accomplished without any cash involved. The broker will do both in a single transaction and use the proceeds of the sale to pay the cost of buying the shares. You should always at least cover the taxable portion of the transaction and typically the broker will withhold that tax anyways. Otherwise you could find yourself in a position where you have actually lost money due to tax being owed while the shares decline in value below that tax. You don't have to worry about that right now. Again as people have mentioned options will typically expire 10 years from vesting or 90 days from leaving your employment with the company. I'm sure there are some variations on the theme. Make sure you ask and all this should be part of some written contract. I'm sure you can ask to see it if you wish. Also typical is that stock option grants have to be approved by the board which is normally a technicality. Some general advice:", "title": "" }, { "docid": "102757", "text": "You bought the stock at some point in the past. You must have had a reason for this purchase. Has the recent change in price changed the reason you bought the stock? You must assume your losses are sunk costs. No matter what action you take, you can not recover your losses. Do not attempt to hold the stock in the hopes of regaining value, or sell it to stop losses. Instead approach this event as if this very day, you were given shares of the company's stock at their current market value for free as a gift. In this hypothetical situation, would you hold the shares, or sell them? Use that to judge your options. Not everyone, myself included, can handle the mental stress of watching share prices change. You can always consider trading index funds instead, which are much less volatile but will provide consistent, albeit, boring returns. This may or may not be you, but it's an option. Finally, do not keep money in the market you are not prepared to lose. It seems obvious, but if you lost 40% today, you could lose 100% tomorrow.", "title": "" }, { "docid": "312679", "text": "Here's the best explanation I found relating to why your T4 box 39 might not have an amount filled in, even when box 38 has one: Department of Finance – Explanatory Notes Relating to the Income Tax Act [...]. It's a long document, but here's the part I believe relevant, with my emphasis: Employee Stock Options ITA 110(1) [...] Paragraph 110(1)(d) is amended to include a requirement that the employee [...] exercise the employee’s rights under the stock option agreement and acquire the securities underlying the agreement in order for the deduction in computing taxable income to be available [...] ensures that only one deduction is available in respect of an employment benefit. In other words, if employee stock option rights are surrendered to an employer for cash or an in-kind payment, then (subject to new subsections 110(1.1) and (1.2)) the employer may deduct the payment but the employee cannot claim the stock option deduction. Conversely, where an employer issues securities pursuant to an employee’s exercise of stock options, the employer can not deduct an amount in respect of the issuance, but the employee may be eligible to claim a deduction under paragraph 110(1)(d). Did you receive real shares based on your participation in the ESPP, or did you get a cash payment for the net value of shares you would have been issued under the plan? From what I can tell, if you opted for a cash payment (or if your plan only allows for such), then the part I emphasized comes into play. Essentially, if conditions were such that your employer could claim a deduction on their corporate income tax return for the compensation paid to you as part of the plan, then you are not also able to claim a similar deduction on your personal income tax return. The money received in that manner is effectively taxed in your hands the same as any bonus employment income would be; i.e. it isn't afforded tax treatment equivalent to capital gains income. Your employer and/or ESPP administrator are best able to confirm the conditions which led to no amount in your box 39, but at least based on above you can see there are legitimate cases where box 38 would have an amount while box 39 doesn't.", "title": "" }, { "docid": "13908", "text": "\"The \"\"par value\"\" is a technicality that you can ignore in this case, and it has nothing directly to do with the merger. When a company issues stock, it puts a \"\"par value\"\" on the shares. If it later issues more shares, they cannot be issued at less than par value. The rest of the notice seems to be as you said: If you hold until the merger takes effect, they are going to give you $25/share and your shares will be gone. As always, you can try to sell on the open market before that time instead, although you can bet that not too many people are going to want to give you more than $25/share at this point.\"", "title": "" }, { "docid": "542764", "text": "\"A stock, at its most basic, is worth exactly what someone else will pay to buy it right now (or in the near future), just like anything else of value. However, what someone's willing to pay for it is typically based on what the person can get from it. There are a couple of ways to value a stock. The first way is on expected earnings per share, most of would normally (but not always) be paid in dividends. This is a metric that can be calculated based on the most recently reported earnings, and can be estimated based on news about the company or the industry its in (or those of suppliers, likely buyers, etc) to predict future earnings. Let's say the stock price is exactly $100 right now, and you buy one share. In one quarter, the company is expected to pay out $2 per share in dividends. That is a 2% ROI realized in 3 months. If you took that $2 and blew it on... coffee, maybe, or you stuffed it in your mattress, you'd realize a total gain of $8 in one year, or in ROI terms an annual rate of 8%. However, if you reinvested the money, you'd be making money on that money, and would have a little more. You can calculate the exact percentage using the \"\"future value\"\" formula. Conversely, if you wanted to know what you should pay, given this level of earnings per share, to realize a given rate of return, you can use the \"\"present value\"\" formula. If you wanted a 9% return on your money, you'd pay less for the stock than its current value, all other things being equal. Vice-versa if you were happy with a lesser rate of return. The current rate of return based on stock price and current earnings is what the market as a whole is willing to tolerate. This is how bonds are valued, based on a desired rate of return by the market, and it also works for stocks, with the caveat that the dividends, and what you'll get back at the \"\"end\"\", are no longer constant as they are with a bond. Now, in your case, the company doesn't pay dividends. Ever. It simply retains all the earnings it's ever made, reinvesting them into doing new things or more things. By the above method, the rate of return from dividends alone is zero, and so the future value of your investment is whatever you paid for it. People don't like it when the best case for their money is that it just sits there. However, there's another way to think of the stock's value, which is it's more core definition; a share of the company itself. If the company is profitable, and keeps all this profit, then a share of the company equals, in part, a share of that retained earnings. This is very simplistic, but if the company's assets are worth 1 billion dollars, and it has one hundred million shares of stock, each share of stock is worth $10, because that's the value of that fraction of the company as divided up among all outstanding shares. If the company then reports earnings of $100 million, the value of the company is now 1.1 billion, and its stock should go up to $11 per share, because that's the new value of one ten-millionth of the company's value. Your ROI on this stock is $1, in whatever time period the reporting happens (typically quarterly, giving this stock a roughly 4% APY). This is a totally valid way to value stocks and to shop for them; it's very similar to how commodities, for instance gold, are bought and sold. Gold never pays you dividends. Doesn't give you voting rights either. Its value at any given time is solely what someone else will pay to have it. That's just fine with a lot of people right now; gold's currently trading at around $1,700 an ounce, and it's been the biggest moneymaker in our economy since the bottom fell out of the housing market (if you'd bought gold in 2008, you would have more than doubled your money in 4 years; I challenge you to find anything else that's done nearly as well over the same time). In reality, a combination of both of these valuation methods are used to value stocks. If a stock pays dividends, then each person gets money now, but because there's less retained earnings and thus less change in the total asset value of the company, the actual share price doesn't move (much). If a stock doesn't pay dividends, then people only get money when they cash out the actual stock, but if the company is profitable (Apple, BH, etc) then one share should grow in value as the value of that small fraction of the company continues to grow. Both of these are sources of ROI, and both are seen in a company that will both retain some earnings and pay out dividends on the rest.\"", "title": "" }, { "docid": "313372", "text": "\"There are a few other items that you should be aware of when getting options: The strike price is usually determined by an independent valuation of the common shares (called a 409a valuation). This should give you a sense on what the options are worth. Obviously you are hoping that the value becomes many multiple of that. There are two kinds in the US: Non-quals (NQO) and Incentive Stock Options (ISOs). The big difference is that when you exercise Non-quals, you have to pay the tax on the difference between the \"\"fair\"\" market value on the shares and what you paid for them (the strike price). This is important because if the company is private, you likely can not sell any shares until it is public. With ISOs, you don't pay any tax (except AMT tax) on the gain until you actually sell the shares. You should know what kind your getting. Some plans allow for early exercise, essentially allowing you to buy the shares early (and given back if you leave before they vest) which helps you establish capital gains treatment earlier as well as avoid AMT if you have ISOs. This is really complicated direction and you would want to talk to a tax professional. And always a good idea to know how many total shares outstanding in the Company. Very few people ask this question but it is helpful for you to understand the overall value of the options.\"", "title": "" }, { "docid": "121622", "text": "\"BigCo is selling new shares and receives the money from Venturo. If Venturo is offering $250k for 25% of the company, then the valuation that they are agreeing on is a value of $1m for the company after the new investment is made. If Jack is the sole owner of one million shares before the new investment, then BigCo sells 333,333 shares to Venturo for $250k. The new total number of shares of BigCo is 1,333,333; Venturo holds 25%, and Jack holds 75%. The amount that Jack originally invested in the company is irrelevant. At the moment of the sale, the Venturo and Jack agree that Jack's stake is worth $750k. The value of Jack's stake may have gone up, but he owes no capital gains tax, because he hasn't realized any of his gains yet. Jack hasn't sold any of his stake. You might think that he has, because he used to hold 100% and now he holds 75%. However, the difference is that the company is worth more than was before the sale. So the value of his stake was unchanged immediately before and after the sale. Jack agrees to this because the company needs this additional capital in order to meet its potential. (See \"\"Why is stock dilution legal?\"\") For further explanation and another example of this, see the question \"\"If a startup receives investment money, does the startup founder/owner actually gain anything?\"\" Your other scenario, where Venturo purchases existing shares directly from Jack, is not practical in this situation. If Jack sells his existing shares, you are correct that the company does not gain any additional capital. An investor would not want to invest in the company this way, because the company is struggling and needs new capital.\"", "title": "" }, { "docid": "64961", "text": "It's great that you have gotten the itch to learn about the stock market. There are a couple of fundamentals to understand first though. Company A has strong, growing, net earnings and minimal debt, it's trading for $100 per share. Company B has good revenue but high costs of goods and total liabilities well in excess of total assets, it's trading for $0.10 per share. There is no benefit to getting 10,000 shares or 10 shares for your $1,000. Your goal is to invest in companies that have valuable products and services run by competent management teams. Sure, the number of shares you own will dictate what percentage of the company you own, and in a number of cases, your voting power. But even a penny stock will have a market capitalization of several million dollars so voting power isn't really a concern for your $1,000 investment. There is a lot more in the three basic financial statements (Income Statement, Balance Sheet, Statement of Cash Flows) than revenue. Seasoned accountants can have a hard time parsing out where money is coming from and where it's going. In general there are obvious red flags, like a fast declining cash balance against a fast growing liabilities balance or expenses exceeding revenue. While some of these things are common among new and high growth companies, it's not the place for a new investor with a small bankroll. A micro-cap company (penny stocks are in this group) will receive rounds of financing via issuing preferred convertible shares which may include options on more shares. For a company worth $20mm a $5mm financing round can materially change the finances of a company, and will likely dilute your holdings in common stock. Small growth companies need new financing frequently to fund their growth strategies. Revenue went up, great... why? Did you open another store? Did you open another sales office? Did the revenue increase this quarter based on substantially the same operation that existed last quarter or have you increased the capacity of your operation? If you increased the capacity of your operation what was the cost of the increase and did revenue increase as expected? Can you expect revenue to continue to grow at this rate or was it a one time windfall from an unusual order? Sure, there are spectacular gains to be had in penny stocks. XYZ Pharma Research (or whatever) goes from $0.05 to $0.60 and you've turned your $1,000 in to $12,000. This is a really unlikely event... Buying penny stocks is akin to buying lottery tickets. Unless you are a high ranking employee at the company capable of making decisions, or one of the investors buying the preferred shares mentioned in point 3, or are one of the insiders of a pump and dump scam on the stock, penny common stocks are not a place to invest. One could argue that even a company insider should probably avoid buying common stock. Just to illustrate the points above, you mention: Doing some really heavy research into this stock has made me question the whole penny stock market. Based on your research what is the enterprise value of the company? What were the gross proceeds of the last financing round, how many shares were issued and were there any warrants attached? What do you perceive to be heavy research? What background do you have in finance/accounting to give weight to your ability to perform such research? Crawl. Walk. Then run. Don't kid yourself in to thinking that since you have some level of education you understand the contracts involved in enterprise finance.", "title": "" }, { "docid": "499811", "text": "Shorting Stocks: Borrowing the shares to sell now. Then buying them back when the price drops. Risk: If you are wrong the stock can go up. And if there are a lot of people shorting the stock you can get stuck in a short squeeze. That means that so many people need to buy the stock to return the ones they borrowed that the price goes up even further and faster. Also whoever you borrowed the stock from will often make the decision to sell for you. Put options. Risk: Put values don't always drop when the underlying price of the stock drops. This is because when the stock drops volatility goes up. And volatility can raise the value of an option. And you need to check each stock for whether or not these options are available. finviz lists whether a stock is optional & shortable or not. And for shorting you also need to find a broker that owns shares that they are willing to lend out.", "title": "" }, { "docid": "107377", "text": "The answer to your question as asked is no. Call options, even those issued by the company, cannot create new shares unless they are employee stock options. Company-issued warrants, on the other hand, can create new shares.", "title": "" }, { "docid": "312811", "text": "\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \"\"actually\"\" and \"\"imaginary\"\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \"\"issuance (retirement) of stock\"\" or the like, so when shares are sold, it is \"\"issuance\"\"; when a company buys back their shares, it's called \"\"retirement\"\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \"\"equity\"\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \"\"common stock\"\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \"\"basic weighted average\"\" and \"\"diluted weighted average\"\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\"", "title": "" }, { "docid": "275199", "text": "I think George's answer explains fairly well why the brokerages don't allow this - it's not an exchange rule, it's just that the brokerage has to have the shares to lend, and normally those shares come from people's margin, which is impossible on a non-marginable stock. To address the question of what the alternatives are, on popular stocks like SIRI, a deep In-The-Money put is a fairly accurate emulation of an actual short interest. If you look at the options on SIRI you will see that a $3 (or higher) put has a delta of -$1, which is the same delta as an actual short share. You also don't have to worry about problems like margin calls when buying options. The only thing you have to worry about is the expiration date, which isn't generally a major issue if you're buying in-the-money options... unless you're very wrong about the direction of the stock, in which case you could lose everything, but that's always a risk with penny stocks no matter how you trade them. At least with a put option, the maximum amount you can lose is whatever you spent on the contract. With a short sale, a bull rush on the stock could potentially wipe out your entire margin. That's why, when betting on downward motion in a microcap or penny stock, I actually prefer to use options. Just be aware that option contracts can generally only move in increments of $0.05, and that your brokerage will probably impose a bid-ask spread of up to $0.10, so the share price has to move down at least 10 cents (or 10% on a roughly $1 stock like SIRI) for you to just break even; definitely don't attempt to use this as a day-trading tool and go for longer expirations if you can.", "title": "" }, { "docid": "21975", "text": "\"In an IPO (initial public offering) or APO (additional public offering) situation, a small group of stakeholders (as few as one) basically decide to offer an additional number of \"\"shares\"\" of equity in the company. Usually, these \"\"shares\"\" are all equal; if you own one share you own a percentage of the company equal to that of anyone else who owns one share. The sum total of all shares, theoretically, equals the entire value of the company, and so with N shares in existence, one share is equivalent to 1/Nth the company, and entitles you to 1/Nth of the profits of the company, and more importantly to some, gives you a vote in company matters which carries a weight of 1/Nth of the entire shareholder body. Now, not all of these shares are public. Most companies have the majority (51%+) of shares owned by a small number of \"\"controlling interests\"\". These entities, usually founding owners or their families, may be prohibited by agreement from selling their shares on the open market (other controlling interests have right of first refusal). For \"\"private\"\" companies, ALL the shares are divided this way. For \"\"public\"\" companies, the remainder is available on the open market, and those shares can be bought and sold without involvement by the company. Buyers can't buy more shares than are available on the entire market. Now, when a company wants to make more money, a high share price at the time of the issue is always good, for two reasons. First, the company only makes money on the initial sale of a share of stock; once it's in a third party's hands, any profit from further sale of the stock goes to the seller, not the company. So, it does little good to the company for its share price to soar a month after its issue; the company's already made its money from selling the stock. If the company knew that its shares would be in higher demand in a month, it should have waited, because it could have raised the same amount of money by selling fewer shares. Second, the price of a stock is based on its demand in the market, and a key component of that is scarcity; the fewer shares of a company that are available, the more they'll cost. When a company issues more stock, there's more shares available, so people can get all they want and the demand drops, taking the share price with it. When there's more shares, each share (being a smaller percentage of the company) earns less in dividends as well, which figures into several key metrics for determining whether to buy or sell stock, like earnings per share and price/earnings ratio. Now, you also asked about \"\"dilution\"\". That's pretty straightforward. By adding more shares of stock to the overall pool, you increase that denominator; each share becomes a smaller percentage of the company. The \"\"privately-held\"\" stocks are reduced in the same way. The problem with simply adding stocks to the open market, getting their initial purchase price, is that a larger overall percentage of the company is now on the open market, meaning the \"\"controlling interests\"\" have less control of their company. If at any time the majority of shares are not owned by the controlling interests, then even if they all agree to vote a certain way (for instance, whether or not to merge assets with another company) another entity could buy all the public shares (or convince all existing public shareholders of their point of view) and overrule them. There are various ways to avoid this. The most common is to issue multiple types of stock. Typically, \"\"common\"\" stock carries equal voting rights and equal shares of profits. \"\"Preferred stock\"\" typically trades a higher share of earnings for no voting rights. A company may therefore keep all the \"\"common\"\" stock in private hands and offer only preferred stock on the market. There are other ways to \"\"class\"\" stocks, most of which have a similar tradeoff between earnings percentage and voting percentage (typically by balancing these two you normalize the price of stocks; if one stock had better dividends and more voting weight than another, the other stock would be near-worthless), but companies may create and issue \"\"superstock\"\" to controlling interests to guarantee both profits and control. You'll never see a \"\"superstock\"\" on the open market; where they exist, they are very closely held. But, if a company issues \"\"superstock\"\", the market will see that and the price of their publicly-available \"\"common stock\"\" will depreciate sharply. Another common way to increase market cap without diluting shares is simply to create more shares than you issue publicly; the remainder goes to the current controlling interests. When Facebook solicited outside investment (before it went public), that's basically what happened; the original founders were issued additional shares to maintain controlling interests (though not as significant), balancing the issue of new shares to the investors. The \"\"ideal\"\" form of this is a \"\"stock split\"\"; the company simply multiplies the number of shares it has outstanding by X, and issues X-1 additional shares to each current holder of one share. This effectively divides the price of one share by X, lowering the barrier to purchase a share and thus hopefully driving up demand for the shares overall by making it easier for the average Joe Investor to get their foot in the door. However, issuing shares to controlling interests increases the total number of shares available, decreasing the market value of public shares that much more and reducing the amount of money the company can make from the stock offering.\"", "title": "" } ]
PLAIN-694	biomarkers	[ { "docid": "MED-4738", "text": "BACKGROUND: Isothiocyanates (ITCs), hydrolysis products from glucosinolates, are a family of biologically active compounds originating from cruciferous vegetables. Many ITCs are assumed to have cancer preventive effects and to further evaluate these potential health effects, reliable biomarkers of ITC exposure are needed. AIM OF THE STUDY: In this study we investigated the ability of urinary ITC excretion to reflect a low or high daily intake of cruciferous vegetables. METHODS: The design was a controlled human crossover study (n = 6). Subjects consumed a self-restricted glucosinolate-free diet 48 h before the study-day where a basic diet supplemented with 80 or 350 g of mixed cruciferous vegetables was consumed. All urine was collected in intervals during the 48 h period after ingestion of the cruciferous vegetables. Total ITC in the cruciferous mixture and total ITC and their metabolites in urine was quantified as the cyclocondensation product of 1,2-bezenedithiol by high performance liquid chromatography. RESULTS: The total urinary excretion of ITCs correlated significantly with the two doses of ITC from diets with high or low cruciferous content (r (s )= 0.90, P < 0.01). The fraction of urinary ITC excreted was 69.02 +/- 11.57% and 74.53 +/- 8.39% of the amounts ingested for 80 and 350 g cruciferous vegetables, respectively. CONCLUSION: The results in this study indicate that the urinary excretion of ITCs, measured by use of the cyclocondesation reaction, is a useful and precise tool that may be used as a biomarker of ITC exposure in population based studies.", "title": "Urinary excretion of total isothiocyanates from cruciferous vegetables shows high dose-response relationship and may be a useful biomarker for isot..." }, { "docid": "MED-4733", "text": "OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish.", "title": "Mercury in human hair as an indicator of the fish consumption." }, { "docid": "MED-4739", "text": "Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.", "title": "Nowhere to hide: Chemical toxicants and the unborn child." }, { "docid": "MED-4735", "text": "BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.", "title": "Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption." }, { "docid": "MED-4736", "text": "OBJECTIVE: Few biomarkers for dietary intake of various food groups have been established. The aim of the present study was to explore whether selenium (Se), iodine, mercury (Hg) or arsenic may serve as a biomarker for total fish and seafood intake in addition to the traditionally used n-3 fatty acids EPA and DHA. DESIGN: Intake of fish and seafood estimated by an FFQ was compared with intake assessed by a 4 d weighed food diary and with biomarkers in blood and urine. SETTING: Validation study in the Norwegian Mother and Child Cohort Study (MoBa). SUBJECTS: One hundred and nineteen women. RESULTS: Total fish/seafood intake (median 39 g/d) calculated with the MoBa FFQ was comparable to intake calculated by the food diary (median 30 g/d, rS = 0.37, P < 0.001). Erythrocyte DHA and blood Hg, Se and arsenic concentrations were positively correlated with intake of fish and seafood, but the association for DHA was weakened by the widespread use of supplements. The main finding was the consistent positive association between the intake of fish/seafood and blood arsenic concentration. In multivariate analyses, blood arsenic was associated with blood Hg and fish and seafood intake. In these models, arsenic turned out to be the best indicator of intake of fish and seafood, both totally and in subgroups of fish/seafood intake. CONCLUSIONS: While DHA reflected the intake of fatty fish and n-3 PUFA supplements, blood arsenic concentration also reflected the intake of lean fish and seafood. Blood arsenic appears to be a useful biomarker for total fish and seafood intake.", "title": "Exploration of biomarkers for total fish intake in pregnant Norwegian women." }, { "docid": "MED-4894", "text": "SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P < 0.001); however, there was no significant correlation between dietary calcium and BMD. Further analysis suggested that whole body BMD, but not lumbar spine or femoral neck BMD, was positively correlated with the ratio of animal protein to vegetable protein. CONCLUSION: These results suggest that, although vegans have much lower intakes of dietary calcium and protein than omnivores, veganism does not have adverse effect on bone mineral density and does not alter body composition.", "title": "Veganism, bone mineral density, and body composition: a study in Buddhist nuns." } ]	[ { "docid": "MED-5193", "text": "BACKGROUND: The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial. OBJECTIVE: We aimed to explore biomarkers of dairy fat intake in plasma and erythrocytes and to assess the hypothesis that higher concentrations of these biomarkers are associated with a greater risk of IHD in US women. DESIGN: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989-1990, 166 incident cases of IHD were ascertained between baseline and 1996. These cases were matched with 327 controls for age, smoking, fasting status, and date of blood drawing. RESULTS: Among controls, correlation coefficients between average dairy fat intake in 1986-1990 and 15:0 and trans 16:1n-7 content were 0.36 and 0.30 for plasma and 0.30 and 0.32 for erythrocytes, respectively. In multivariate analyses, with control for age, smoking, and other risk factors of IHD, women with higher plasma concentrations of 15:0 had a significantly higher risk of IHD. The multivariate-adjusted relative risks (95% CI) from the lowest to highest tertile of 15:0 concentrations in plasma were 1.0 (reference), 2.18 (1.20, 3.98), and 2.36 (1.16, 4.78) (P for trend = 0.03). Associations for other biomarkers were not significant. CONCLUSIONS: Plasma and erythrocyte contents of 15:0 and trans 16:1n-7 can be used as biomarkers of dairy fat intake. These data suggest that a high intake of dairy fat is associated with a greater risk of IHD.", "title": "Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease." }, { "docid": "MED-1511", "text": "Aims Prolonged sedentary time is ubiquitous in developed economies and is associated with an adverse cardio-metabolic risk profile and premature mortality. This study examined the associations of objectively assessed sedentary time and breaks (interruptions) in sedentary time with continuous cardio-metabolic and inflammatory risk biomarkers, and whether these associations varied by sex, age, and/or race/ethnicity. Methods and results Cross-sectional analyses with 4757 participants (≥20 years) from the 2003/04 and 2005/06 US National Health and Nutrition Examination Survey (NHANES). An Actigraph accelerometer was used to derive sedentary time [<100 counts per minute (cpm)] and breaks in sedentary time. Independent of potential confounders, including moderate-to-vigorous exercise, detrimental linear associations (P for trends <0.05) of sedentary time with waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, HOMA-%B, and HOMA-%S were observed. Independent of potential confounders and sedentary time, breaks were beneficially associated with waist circumference and C-reactive protein (P for trends <0.05). There was limited evidence of meaningful differences in associations with biomarkers by age, sex, or race/ethnicity. Notable exceptions were sex-differences in the associations of sedentary time and breaks with HDL-cholesterol, and race/ethnicity differences in the association of sedentary time with waist circumference with associations detrimental in non-Hispanic whites, null in Mexican Americans, and beneficial in non-Hispanic blacks. Conclusion These are the first population-representative findings on the deleterious associations of prolonged sedentary time with cardio-metabolic and inflammatory biomarkers. The findings suggest that clinical communications and preventive health messages on reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk.", "title": "Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003–06" }, { "docid": "MED-5358", "text": "Alkylresorcinols (ARs) are shown to be good biomarkers of consumption of rye and whole-grain wheat products in man. The aim of this pilot study was to investigate AR metabolites as potential biomarkers of breast cancer (BC) risk in Finnish women since intake of cereal fiber and its components has been proposed to reduce this risk through an effect on the enterohepatic circulation of estrogens. This was a cross-sectional and observational pilot study. A total of 20 omnivores, 20 vegetarians, and 16 BC women (6-12 mo after operation) were investigated on 2 occasions 6 mo apart. Dietary intake (5-days record), plasma/urinary AR metabolites [3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA)] and plasma/urinary enterolactone were measured. The groups were compared using nonparametric tests. We observed that plasma DHBA (P = 0.007; P = 0.03), plasma DHPPA (P = 0.02; P = 0.01), urinary DHBA (P = 0.001; P = 0.003), urinary DHPPA (P = 0.001; P = 0.001), and cereal fiber intake (P = 0.007; P = 0.003) were significantly lower in the BC group compared to the vegetarian and omnivore groups, respectively. Based on measurements of AR metabolites in urine and in plasma, whole-grain rye and wheat cereal fiber intake is low in BC subjects. Thus, urinary and plasma AR metabolites may be used as potential biomarkers of BC risk in women. This novel approach will likely also facilitate studies of associations between rye and whole-grain wheat cereal fiber intake and other diseases. Our findings should, however, be confirmed with larger subject populations.", "title": "Plasma and urinary alkylresorcinol metabolites as potential biomarkers of breast cancer risk in Finnish women: a pilot study." }, { "docid": "MED-4206", "text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.", "title": "Vegetarian diets and public health: biomarker and redox connections." }, { "docid": "MED-4687", "text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.", "title": "Vegetarian diets and public health: biomarker and redox connections." }, { "docid": "MED-2411", "text": "The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.", "title": "Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis" }, { "docid": "MED-1682", "text": "Background The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products. Methods We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair. Results Plasma vitamin C increased after supplementation as did resistance towards H2O2-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation. Conclusion Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.", "title": "Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection" }, { "docid": "MED-2523", "text": "Background The ‘Blood-Type’ diet advises individuals to eat according to their ABO blood group to improve their health and decrease risk of chronic diseases such as cardiovascular disease. However, the association between blood type-based dietary patterns and health outcomes has not been examined. The objective of this study was to determine the association between ‘blood-type’ diets and biomarkers of cardiometabolic health and whether an individual's ABO genotype modifies any associations. Methods Subjects (n = 1,455) were participants of the Toronto Nutrigenomics and Health study. Dietary intake was assessed using a one-month, 196-item food frequency questionnaire and a diet score was calculated to determine relative adherence to each of the four ‘Blood-Type’ diets. ABO blood group was determined by genotyping rs8176719 and rs8176746 in the ABO gene. ANCOVA, with age, sex, ethnicity, and energy intake as covariates, was used to compare cardiometabolic biomarkers across tertiles of each ‘Blood-Type’ diet score. Results Adherence to the Type-A diet was associated with lower BMI, waist circumference, blood pressure, serum cholesterol, triglycerides, insulin, HOMA-IR and HOMA-Beta (P<0.05). Adherence to the Type-AB diet was also associated with lower levels of these biomarkers (P<0.05), except for BMI and waist circumference. Adherence to the Type-O diet was associated with lower triglycerides (P<0.0001). Matching the ‘Blood-Type’ diets with the corresponding blood group did not change the effect size of any of these associations. No significant association was found for the Type-B diet. Conclusions Adherence to certain ‘Blood-Type’ diets is associated with favorable effects on some cardiometabolic risk factors, but these associations were independent of an individual's ABO genotype, so the findings do not support the ‘Blood-Type’ diet hypothesis.", "title": "ABO Genotype, ‘Blood-Type’ Diet and Cardiometabolic Risk Factors" }, { "docid": "MED-2276", "text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.", "title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans." }, { "docid": "MED-2830", "text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.", "title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks." }, { "docid": "MED-1389", "text": "BACKGROUND & AIMS: Metabolic syndrome (MetS), in which a non-classic feature is an increase in systemic oxidative biomarkers, presents a high risk of diabetes and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet) is associated with a reduced risk of MetS. However, the effect of the MedDiet on biomarkers for oxidative damage has not been assessed in MetS individuals. We have investigated the effect of the MedDiet on systemic oxidative biomarkers in MetS individuals. METHODS: Randomized, controlled, parallel clinical trial in which 110 female with MetS, aged 55-80, were recruited into a large trial (PREDIMED Study) to test the efficacy of the traditional MedDiet on the primary prevention of CVD. Participants were assigned to a low-fat diet or two traditional MedDiets (MedDiet + virgin olive oil or MedDiet + nuts). Both MedDiet group participants received nutritional education and either free extra virgin olive oil for all the family (1 L/week), or free nuts (30 g/day). Diets were ad libitum. Changes in urine levels of F2-Isoprostane (F2-IP) and the DNA damage base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) were evaluated at 1-year trial. RESULTS: After 1-year urinary F2-IP decreased in all groups, the decrease in MedDiet groups reaching a borderline significance versus that of the Control group. Urinary 8-oxo-dG was also reduced in all groups, with a higher decrease in both MedDiet groups versus the Control one (P < 0.001). CONCLUSIONS: MedDiet reduces oxidative damage to lipids and DNA in MetS individuals. Data from this study provide evidence to recommend the traditional MedDiet as a useful tool in the MetS management. Registered under Clinical Trials.gov Identifier no. NCT00123456. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "title": "The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial." }, { "docid": "MED-4097", "text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.", "title": "Green Tea and Breast Cancer" }, { "docid": "MED-3866", "text": "Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.", "title": "Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design" }, { "docid": "MED-4553", "text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.", "title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?" }, { "docid": "MED-3921", "text": "BACKGROUND: To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). RESULTS: HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). CONCLUSION: The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.", "title": "Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects." }, { "docid": "MED-4978", "text": "Human risk assessment of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the diet may be improved by conducting biomonitoring studies comparing metabolism in humans and rodents. Eleven volunteers ingested a meal of cooked chicken containing 4 -OH-PhIP and PhIP in amounts of 0.6 and 0.8microg/kg, respectively and urine was collected for the next 16h. The large number of PhIP metabolites was by treatment of the urine samples with hydrazine hydrate and hydrolytic enzymes reduced to three substances, 4'-OH-PhIP, PhIP and 5-OH-PhIP of which the first is a biomarker for detoxification and the last a biomarker for activation. The eleven volunteers eliminated large amounts of 4'-OH-PhIP in the urine. The majority of which could be accounted for by the presence of 4'-OH-PhIP in the fried chicken, showing that PhIP only to a small extent (11%) was metabolised to 4'-OH-PhIP. A larger fraction of the PhIP exposure, 38%, was recovered as PhIP and the largest fraction (51%) was recovered as 5-OH-PhIP suggesting that PhIP in humans to a large extent is metabolised to reactive substances. In rats, less than 1% of the dose of PhIP was eliminated as 5-OH-PhIP, suggesting that human cancer risk from exposure to PhIP is considerable higher than risk estimations based on extrapolation from rodent bioassays.", "title": "Biomonitoring of urinary metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) following human consumption of cooked chicken." }, { "docid": "MED-1711", "text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.", "title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer" }, { "docid": "MED-2226", "text": "BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.", "title": "Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults." }, { "docid": "MED-3833", "text": "Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women.", "title": "Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)" }, { "docid": "MED-3841", "text": "Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women.", "title": "Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)" }, { "docid": "MED-4973", "text": "Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for assessing human exposure to PAHs. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) uses OH-PAHs to establish reference range concentrations for the US population, and to set benchmarks for future epidemiologic and biomonitoring studies. For the years 2001 and 2002, 22 OH-PAH metabolites were measured in urine specimens from 2748 NHANES participants. Percentages of samples with detectable levels ranged from nearly 100% for metabolites of naphthalene, fluorene, phenanthrene, and pyrene, to less than 5% for metabolites from parent compounds with higher molecular weight such as chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The geometric mean for 1-hydroxypyrene (1-PYR)--the most commonly used biomarker for PAH exposure--was 49.6 ng/L urine, or 46.4 ng/g creatinine. Children (ages 6-11) generally had higher levels than did adolescents (ages 12-19) or adults (ages 20 and older). Model-adjusted, least-square geometric means for 1-PYR were 87, 53 and 43 ng/L for children, adolescents (ages 12-19) and adults (ages 20 years and older), respectively. Log-transformed concentrations for major detectable OH-PAHs were significantly correlated with each other. The correlation coefficients between 1-PYR and other metabolites ranging from 0.17 to 0.63 support the use of 1-PYR as a useful surrogate representing PAH exposure.", "title": "Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population." }, { "docid": "MED-5087", "text": "Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted. (c) 2008 Wiley-Liss, Inc.", "title": "Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study." }, { "docid": "MED-1063", "text": "BACKGROUND: The results of some epidemiologic studies conducted by using questionnaires suggest that dietary fat composition influences diabetes risk. Confirmation of this finding with use of a biomarker is warranted. OBJECTIVE: We prospectively investigated the relation of plasma cholesterol ester (CE) and phospholipid (PL) fatty acid composition with the incidence of diabetes mellitus. DESIGN: In 2909 adults aged 45-64 y, plasma fatty acid composition was quantified by using gas-liquid chromatography and was expressed as a percentage of total fatty acids. Incident diabetes (n = 252) was identified during 9 y of follow-up. RESULTS: After adjustment for age, sex, baseline body mass index, waist-to-hip ratio, alcohol intake, cigarette smoking, physical activity, education, and parental history of diabetes, diabetes incidence was significantly and positively associated with the proportions of total saturated fatty acids in plasma CE and PL. The rate ratios of incident diabetes across quintiles of saturated fatty acids were 1.00, 1.36, 1.16, 1.60, and 2.08 (P = 0.0013) in CE and 1.00, 1.75, 1.87, 2.40, and 3.37 (P < 0.0001) in PL. In CE, the incidence of diabetes was also positively associated with the proportions of palmitic (16:0), palmitoleic (16:1n-7), and dihomo-gamma-linolenic (20:3n-6) acids and inversely associated with the proportion of linoleic acid (18:2n-6). In PL, incident diabetes was positively associated with the proportions of 16:0 and stearic acid (18:0). CONCLUSIONS: The proportional saturated fatty acid composition of plasma is positively associated with the development of diabetes. Our findings with the use of this biomarker suggest indirectly that the dietary fat profile, particularly that of saturated fat, may contribute to the etiology of diabetes.", "title": "Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study." }, { "docid": "MED-2076", "text": "BACKGROUND: Berries are a particularly rich source of polyphenols. They also contain other bioactive substances, such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods (eg, cocoa, tea, and red wine) may induce beneficial changes in pathways related to cardiovascular health. Whether the consumption of berries has similar effects is unknown. OBJECTIVE: We aimed to investigate the effects of berry consumption on hemostatic function, serum lipids, and blood pressure (BP). DESIGN: Middle-aged unmedicated subjects (n = 72) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind, randomized, placebo-controlled intervention trial. RESULTS: Berry consumption inhibited platelet function as measured with a platelet function analyzer (using collagen and ADP as platelet activator) [changes: 11% and -1.4% in the berry and control groups, respectively; P = 0.018, analysis of covariance (ANCOVA)]. Plasma biomarkers of platelet activation, coagulation, and fibrinolysis did not change during the intervention. Serum HDL-cholesterol concentrations increased significantly more (P = 0.006, ANCOVA) in the berry than in the control group (5.2% and 0.6%, respectively), but total cholesterol and triacylglycerol remained unchanged. Systolic BP decreased significantly (P = 0.050, ANCOVA); the decrease mostly occurred in subjects with high baseline BP (7.3 mm Hg in highest tertile; P = 0.024, ANCOVA). Polyphenol and vitamin C concentrations in plasma increased, whereas other nutritional biomarkers (ie, folate, tocopherols, sodium, and potassium) were unaffected. CONCLUSION: The consumption of moderate amounts of berries resulted in favorable changes in platelet function, HDL cholesterol, and BP. The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease.", "title": "Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol." }, { "docid": "MED-2386", "text": "OBJECTIVE Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes. RESEARCH DESIGN AND METHODS We used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Associations of mercury exposure with incident diabetes were assessed using Cox proportional hazards. RESULTS During mean ± SD follow-up of 19.7 ± 7.0 years, 1,010 new cases of diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 μg/g in men and 0.76 μg/g in women, corresponding to exposures ∼3.5-fold and 2-fold higher than the U.S. Environmental Protection Agency reference dose. In multivariable analyses, toenail mercury concentrations were not associated with higher incidence of diabetes in women, men, or both cohorts combined. Comparing the highest to lowest quintile of exposure, the hazard ratio (95% CI) for incident diabetes was 0.86 (0.66–1.11) in women, 0.69 (0.42–1.15) in men, and 0.77 (0.61–0.98) in the combined cohorts. Findings were similar when more extreme categories (deciles) of mercury were compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age. CONCLUSIONS These findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.", "title": "Methylmercury Exposure and Incident Diabetes in U.S. Men and Women in Two Prospective Cohorts" }, { "docid": "MED-4059", "text": "2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.", "title": "Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans." }, { "docid": "MED-4458", "text": "Background Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine with keto-enol tautomerase activity, rises rapidly in response to inflammation, and is elevated in many chronic diseases. Isothiocyanates, such as sulforaphane from broccoli, are very potent inactivators of MIF tautomerase activity. A simple rapid method for determining this activity in tissues and body fluids may therefore be valuable for assessing severity of inflammation and efficacy of intervention. Methods Existing spectrophotometric assays of MIF, based on conversion of methyl L-dopachrome to methyl 5,6-dihydroxyindole-2-carboxylate and associated loss of absorption at 475 nm, lack sensitivity. Assay sensitivity and efficiency were markedly improved by reducing the nonenzymatic rate, by lowering pH to 6.2, replacing phosphate (which catalyzes the reaction) with Bis-Tris buffer, and converting to a microtiter plate format. Results A structure-potency study of MIF tautomerase inactivation by isothiocyanates showed that sulforaphane, benzyl, n-hexyl, and phenethyl isothiocyanates were especially potent. MIF tautomerase could be readily quantified in human urine concentrated by ultrafiltration. This activity comprised: (i) a heat-labile, sulforaphane-inactivated macromolecular fraction (presumably MIF) that was concentrated during ultrafiltration; (ii) a flow-through fraction, with constant activity during filtration, that was heat-stable, and insensitive to sulforaphane. Administration of the sulforaphane precursor glucoraphanin to human volunteers almost completely abolished urinary tautomerase activity, which was recovered over many hours. Conclusions A simple, rapid, quantitative MIF tautomerase assay has been developed as a potential biomarker for assessing inflammatory severity and effectiveness of intervention. Impact An improved assay for measuring MIF tautomerase activity and its applications are described.", "title": "Inactivation of Tautomerase Activity of Macrophage Migration Inhibitory Factor by Sulforaphane: A Potential Biomarker for Anti-inflammatory Intervention" }, { "docid": "MED-3444", "text": "Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in \"low-risk\" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in \"high-risk\" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.", "title": "Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study." }, { "docid": "MED-5012", "text": "This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.", "title": "The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol." }, { "docid": "MED-1338", "text": "Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.", "title": "Milk intake and risk of mortality and fractures in women and men: cohort studies" } ]
2455	Gift card fraud: To whom to report? How to recover funds? Is the party which issued me the card liable?	[ { "docid": "596284", "text": "Question 1: Who do I report such fraud to? Walmart, or their card processor. They may be in their right to require the original purchaser to do the report. Generally, credit card and debit card fraud must be reported to the bank within 60 days of the statement for them to take responsibility. I don't see why gift cards would be different. You can also report it to the police, but I believe you'll be asked to file a report in the jurisdiction where the card was used. Again - time is of the essence, and there's nothing much they could do with your report now. Question 2: How can I recover the $100 value of my Walmart gift card? At this point, 2.5 years later when the card was used to buy prepaid cards, there's no way to catch the thief and recover the funds. Had you reported it promptly, Wlamart could have block the prepaid cards sold or track their usage, but now is too late. Question 3: Is Citibank in any way liable? (The gift card was fraudulently used shortly after---within the same month---I received it from Citibank.) I doubt it unless you can show a pattern. It could be someone working for the Citibank, someone working for the USPS, or someone just stole a bunch of numbers and waited until they became activated.", "title": "" }, { "docid": "129034", "text": "Have you checked to see if anything else went missing? Walmart says that because I was not the original purchaser of the gift card, they could not help me directly Just to build on what @littleadv already gave you, my personal experience on this is that none of the companies that you'll likely be dealing with in a situation like this will be falling over themselves to help you out. Unless it also helps them for some reason, or if they're compelled by consumer laws. If you think you should be protected from this sort of thing happening, feel free to reference the FCRA to see if you might get any consumer protections. But just from what you've said here, it doesn't sound like you do. So if anything else went missing (or even if not), it might have been someone working for Citi, who may have had access to more of your personal information than just your card. ID theft is unfortunately common, as a fairly easy crime to commit, a hard one to protect yourself against, and a very hard one to prosecute. When did you last check your credit report?", "title": "" }, { "docid": "478124", "text": "Citibank just sent me a $100 check. Here's how I got it:", "title": "" } ]	[ { "docid": "456887", "text": ">> Hey! Do you mind giving your credit card to the waiter... > I'm not especially fond of that, but it's easy to report fraud to the bank and most of the time the bank will reverse the charges. No kidding! Of course, even I give credit cards to waiters. What do I care? As you said, you are not liable to any fraud on your credit card. None at all!!!! It's only Merchant, not the credit card company, that pay the price for fraud... and you pay higher prices to cover for losses from fraud. > The PIN situation is different because a mugging is life-threatening. Nonsense! Mugging at the ATM is so rare, each ATM has a camera. In any case, I am not talking about using PIN to withdraw money! I am talking about PIN to authorize charges on a credit card or ATM card. >> We already determined that nobody even care about signatures or check them. > You can't use a stolen card at an ATM with a signature. Huh? You totally got it wrong what I said, or, you argue for the sake of argument. I am saying that cards that require you to enter a PIN cannot be used used when stolen or copied. Yes or no? On the other hand, cards that require signature can be used when stolen or copied because signature is a worthless method to validate the charge. Yes or no? LASTLY, my Costco credit card has a picture of me on it. Question for you, since for some reason you argue so much against PINs: Wouldn't a picture on the card better than a signature? Yes or no? Do you see? There are so many ways to make this system so much more secure and fraud proof... but, ON PURPOSE, the credit card companies don't want that... because they are not liable for fraud. Simple as that.", "title": "" }, { "docid": "5191", "text": "Credit card fraud protection (by law), credit card cash back programs (provided by most CC issuers), and debit card fees (commonly imposed by the merchant). The crux is that with CC transactions, a small percentage is remitted to the issuing bank. Since the banks are already making money hand over fist on CC's, they incentivize people to use them. CC security is also lax because the merchant is responsible for fraudulent charges instead of the bank. If the merchant fails to check a signature, they are held liable for all charges if the card holder reports a fraudulent transaction.", "title": "" }, { "docid": "298729", "text": "\"I completely agree with @littleadv in favor of using the credit card and dispute resolution process, but I believe there are more important details here related to consumer protection. Since 1968, US citizens are protected from credit card fraud, limiting the out-of-pocket loss to $50 if your card is lost, stolen, or otherwise used without your permission. That means the bank can't make you pay more than $50 if you report unauthorized activity--and, nicely, many credit cards these days go ahead and waive the $50 too, so you might not have to pay anything (other than the necessary time and phone calls). Of course, many banks offer a $50 cap or no fees at all for fraudulent charges--my bank once happily resolved some bad charges for me at no loss to me--but banks are under no obligation to shield debit card customers from fraud. If you read the fine print on your debit card account agreement you may find some vague promises to resolve your dispute, but probably nothing saying you cannot be held liable (the bank is not going to lose money on you if they are unable to reverse the charges!). Now a personal story: I once had my credit card used to buy $3,000 in stereo equipment, at a store I had never heard of in a state I have never visited. The bank notified me of the surprising charges, and I was immediately able to begin the fraud report--but it took months of calls before the case was accepted and the charges reversed. So, yes, there was no money out of my pocket, but I was completely unable to use the credit card, and every month they kept on piling on more finance fees and late-payment charges and such, and I would have to call them again and explain again that the charges were disputed... Finally, after about 8 months in total, they accepted the fraud report and reversed all the charges. Lastly, I want to mention one more important tool for preventing or limiting loss from online purchases: \"\"disposable\"\", one-time-use credit card numbers. At least a few credit card providers (Citibank, Bank of America, Discover) offer you the option, on their websites, to generate a credit card number that charges your account, but under the limits you specify, including a maximum amount and expiration date. With one of these disposable numbers, you can pay for a single purchase and be confident that, even if the number were stolen in-transit or the merchant a fraud, they don't have your actual credit card number, and they can never charge you again. I have not yet seen this option for debit card customers, but there must be some banks that offer it, since it saves them a lot of time and trouble in pursuing defrauders. So, in short: If you pay with a credit card number you will not ever have to pay more than $50 for fraudulent charges. Even better, you may be able to use a disposable/one-time-use credit card number to further limit the chances that your credit is misused. Here's to happy--and safe--consumering!\"", "title": "" }, { "docid": "286992", "text": "\"Is there a solution here that would allow me to provide him with a debit card in his name that I could fund, that wouldn't have foreign transaction fees associated with it (I'd probably be okay with a small fixed ATM fee). There are separate issues here. There is no law limiting bank accounts to U.S. citizens, but most banks will not open an account for a non-citizen outside their declared service area. There are substantial legal liabilities to the bank in allowing it, whether a citizen or non-citizen. The difficulty will be compliance with the Patriot Act. This is an extension of the older \"\"Know Your Customer\"\" doctrine. It is improbable that the bank could comply with the Act without the potential customer being physically present. You would have to check with your bank in advance as to their policies. Banks are not required to accept a customer outside their policies. As to waiving the foreign transaction fee, that is very improbable. Although a handful of institutions do this in specific cases it is uncommon because the bank isn't actually charging the fee, they are passing it along. With a credit card they collect interest and waiving the fee can be thought of as a reduction in interest income, that isn't possible on a debit card. You would want to make sure you have a scrupulously honest nephew. You could be held criminally liable for any actions he takes at both the state and the federal level. U.S. law is global. A citizen who commits a crime in any country of the world can be charged for it in the United States. By being on the account you can acquire any liabilities that are created as an accomplice. This is a bigger issue at the federal level because 4,000 federal laws do not require criminal intent. Some do not require you to even know the action happened. Unlike state law which generally requires you intended to commit a crime and had to be aware of it, federal law often does not. It is also not adequate that the action is legal in Russia if it would be illegal in the United States. If I get a card in my name, and give it to him to use to withdraw money from ATMs, is that legal? What problems might that cause? It is legal, but you are now strictly liable for its use. See the above answer. It would probably get shut down anyway when they phone you and asked: \"\"are you in Russia right now?\"\" The bank is still liable for you giving away the card. The bank may close out all your accounts and submit a currency transaction report on you to the Treasury for possible money laundering. Wire the money. Plan out how much and when, but just wire it.\"", "title": "" }, { "docid": "407757", "text": "There's no need for joint accounts to transfer money between you. You can always transfer money to him in Israel to his Israeli account. Having joint account will pose a couple of issues. If the account is in Israel - you will be liable for FBAR/FATCA reports. If the account is in the US - your son will be liable for similar reports in Israel. Joint account also means there's an ambiguity about what belongs to whom and is transferred in what direction. You'll have issues with gift tax reporting/liabilities. Your son can open a USD account in Israel and you can wire money there or send him checks (that would take longer). Or, you can wire money directly to his ILS account.", "title": "" }, { "docid": "581889", "text": "First thing to do when you notice a credit card fraud is to call the respective banks who issues the credit card and most banks immediately (as far as my experience goes - twice) they will cancel the credit card and issue a new card with different number. Your credit card account will remain the same, no effect on credit score as the account is still active, its just the credit card number is changed. If you are more concerned about Identity Theft, there are two further options you can pursue. Place a Fraud Alert : Ask 1 of the 3 credit reporting companies to put a fraud alert on your credit report. They must tell the other 2 companies. An initial fraud alert can make it harder for an identity thief to open more accounts in your name. The alert lasts 90 days but you can renew it. - as per Federal Trade Commission Credit Freeze : If you’re concerned about identity theft, those reported mega-data breaches, or someone gaining access to your credit report without your permission, you might consider placing a credit freeze on your report. - as per Federal Trade Commission", "title": "" }, { "docid": "454951", "text": "\"Does the money lending between us need to be reported in our tax reports? No. Will he be taxed more because of lending the money to me? Yes. Will I be taxed more because of borrowing the money from him? No. How shall we report it so as to minimize our taxes? You cannot. What is reported on your tax returns is the income. A loan is not an income, so nothing gets reported. However, when you repay the loan, assuming it has interest, the lender has income: the interest. Interest income is reported on schedule B of the regular (1040/1040A) tax return (or, in the case of non-resident for tax purposes, on line 9 of 1040NR). It is taxed as ordinary income, and since you're both foreigners - the lender should look into the treaty provisions that might be relevant. Generally it is not exempt from taxable income based on treaty exemptions for students (which is only for earned income), but there might be other rules in the treaty regarding interest income. If there's no (fair market or higher) interest, then there's \"\"assumed\"\" interest at the IRS mandated rates, which is considered a gift. If it amounts to more than the yearly gift exemption, the lender may be liable for gift tax (depending on the lender's and your status, and again - see treaties). \"\"Loan\"\" without an obligation to repay and without actual repaying will also be considered a gift for tax purposes. If the lender has no intentions of having the loan repaid (i.e.: making a gift), it will be better to pay your tuition bills instead of actually giving you the money: tuition is exempt from gift tax. Talk to a CPA/EA licensed in your state for a proper tax advice on this issue.\"", "title": "" }, { "docid": "404833", "text": "I actually just did that with my Chase Freedom card. They rotate categories every 3 months, and from April-June it was 5% back at grocery stores. So I bought a ton of gas cards and got my 5% back. Next I figured out I would be clever and buy a ton of store gift cards (grocery gift cards) right at the end of the quarter, then use those in the future to purchase gas cards. Well, I just tried that a couple days ago and discovered the store refuses to sell a gift card if you're paying with a gift card! So now I'm stuck with $1,000 in grocery cards until I use them in actual grocery purchases haha One of the things about this grocery store is they partner with a gas station on their rewards program. They offer 10 cents off a gallon with every $100 spent in store, and they double it to 20 cents off a gallon if you buy $100 in gift cards. Then on the back of the receipt is a coupon for 10 cents off per gallon -- which they double on Tuesdays. Unfortunately I think I'm one of the only people that takes this much advantage of the program :-/ Side note: I actually just changed the billing cycle of my Chase Freedom card to end on the 24th of the month. That way I can charge a bunch of rewards in the final 6-7 days of the quarter. And if I have a $0 balance on the 24th, my bill isn't due for 7 weeks -- interest free! And Chase Freedom has never cared if you purchase gift cards with their quarterly rewards program. I also gave them a courtesy email giving the specific store and $$$ amount that was going to be charged, and of course they still called me with a 'fraud alert'...", "title": "" }, { "docid": "447478", "text": "I don't know of any that are comparable to credit cards. There's a reason for that. Debit cards, being newer, have a much lower interchange rate. Since collecting on debt is risky and less predictable, rewards / miles are paid from those interchange fees. This means with a debit card there's less money to pay you with. So what can you do? Assuming your credit isn't terrible, you can just open a credit card account and pay in full for purchases by the grace period. I don't know how all cards work, but my grace period allows me to pay in full by the billing date (roughly a month from purchase) and incur no finance charges. In effect, I get a small 30 day loan with no interest, and a cash back incentive (I dislike miles). You're also less liable for fraud via CC than debit.", "title": "" }, { "docid": "277039", "text": "You need to find out exactly how the two accounts are titled. If an account is an UGMA (Uniform Gifts to Minors Act) account that is in your name with your mother/father as custodian, then you are entitled to all the money in the account when you become an adult. If the account is indeed a UGMA account, the bank is supposed to not let the custodian operate the account once the child becomes an adult, but this does not always happen. There was a question earlier on money.SE (which I cannot find at this time) in which the 25-year-old person asking the question claimed that his father was still buying and selling shares in his UGMA brokerage account and the IRS was asking why the profits and losses from these transactions were not being reported on the 25-year-old's tax return. Money in an UGMA account is not supposed to be used for payment of household expenses, food, etc. which is the parent's responsibility during the minority, but this can well be abused. As to whether money was taken out and then restored (or possibly not restored, as you seem to suspect), it is possible to sue the custodian for improper handling of the UGMA account and recover the funds, but whether one wants to sue a parent over what might be a relatively small sum is another matter. Consider whether most of what is recovered might go to pay legal fees or other costs of the recovery process, and will likely ruin a family relationship. If the accounts are titled as joint accounts, then either party can empty the account without informing the other. But doing so would need information about the account number etc. which you may not have. For tax purposes, there is also the issue of whose Social Security Number is listed on the account, yours or your parent's. See also this answer for a view of what happens from the other side.", "title": "" }, { "docid": "325904", "text": "In addition to what has been said, gift cards with a credit card logo (which is what I am assuming you mean here) do not have an address associated with them. That means that if you try to use one at a merchant that users address verification (common in online purchases), the transaction will fail. In my experience with an American Express branded gift card, I was able to call the number on the back and they added an address to the card so that it would work. It seemed like this was a common and well known issue. Because the gift card is not associated with any person, no verification is needed to add that address, you can give them any address you want. Also I believe that the card numbers in use for gift cards are specific, that is you could tell that a card is a gift card based on the number alone. That means it is likely possible for a merchant to reject those gift cards while still accepting other cards from that network. This is likely for certain transactions. For example, a hotel or car rental agency requires a credit card for incidentals, and it's likely that the system itself will outright reject a gift card even if it has enough on it for the initial hold. As for debit cards, I think there are far fewer issues with acceptance, other than the aforementioned hold issues described in another answer.", "title": "" }, { "docid": "520205", "text": "Patience is the key here, I hate to say! There are five factors to FICO credit scores: Payment history is adversely affected by late payments - so always pay on time, otherwise your report will be haunted for seven years! 👻 Credit utilization has to do with how much of your available credit is currently in use - lower is better, but 0% isn't good either because they want to see that you're using credit. 10% or less is a good goal, and try to keep any single card balance to 30% or less when its statement close date rolls around. Credit history is based on the average age of all of your accounts, cards or otherwise, the older the better. Don't close either of your other cards (because that would cause your average account age to fall), and make sure to use the store card at least occasionally, because lenders sometimes decide to close unused lines of credit. Credit mix has to do with the different types of credit you hold and is why your bank's website suggested taking out a loan. It also has to do with the number of accounts overall; I've never found a satisfactory answer for what the sweet spot is, but I suspect it's in the 6-12 range? You wouldn't want to get several new ones at the same time because... New credit is affected by the credit inquiries (hard pulls) that occur when you apply for new cards or loans. Inquiries stay on your report for two years before falling off. This is almost certainly where your score dropped. You also mentioned not knowing if some hospital bills are still affecting your score. You'll want to review your credit reports and find out, plus checking your credit reports regularly is a really great habit to get into because errors (and fraud) can and do happen. There are three credit reporting agencies: Experian, Equifax, and TransUnion, and you'll want to review all three. You can get one free report from each of them every year: https://www.usa.gov/credit-reports It can take a couple of months for a new credit account to show up on your credit report, so your score should recover and go even higher once that happens. Sit tight, as annoying as that is!", "title": "" }, { "docid": "30299", "text": "\"As indicated in comments, this is common practice in the US as well as EU. For example, in this Fox Business article, a user had basically the same experience: their card was replaced but without the specific merchant being disclosed. When the reporter contacted Visa, they were told: \"\"We also believe that the public interest is best served by quickly notifying financial institutions with the information necessary to protect themselves and their cardholders from fraud losses. Even a slight delay in notification to financial institutions could be costly,” the spokesperson said in an e-mail statement. “Visa works with the breached entity to collect the necessary information and provides payment card issuers with the affected account numbers so they can take steps to protect consumers through independent fraud monitoring, and if needed, reissuing cards. The most critical information needed is the affected accounts, which Visa works to provide as quickly as possible.” What they're not saying, of course, is that it's in Visa's best interests that merchants let Visa know right away when a leak occurs, without having to think about whether it's going to screw that merchant over in the press. If the merchant has to consider PR, they may not let the networks know in as timely of a fashion - they may at least wait until they've verified the issue in more detail, or even wait until they've found who to pin it on so they don't get blamed. But beyond that, the point is that it's easier for the network (Visa/Mastercard/etc.) to have a system that's just a list of card numbers to submit to the bank for re-issuing; nobody there really cares which merchant was at fault, they just want to re-issue the cards quickly. Letting you know who's at fault is separate. There's little reason for the issuing bank to ever know; you should find out from the merchant themselves or from the network (and in my experience, usually the former). Eventually you may well find out - the article suggest that: [T]he situation is common, but there is some good news: consumers do in many cases find out the source of the breach. But of course doesn't go into detail about numbers.\"", "title": "" }, { "docid": "265453", "text": "\"With regard to your edit (although I didn't downvote): one way to reduce the security risk is to separate the payment from the ability to drain your account. A considerable part of the security risk is inherent in giving people a number which is directly linked to a bank account where you keep all your money. If you don't want that risk, don't do that. Instead of (or in addition to) trying to reduce the chance of fraud, you can reduce the impact of fraud, even if it occurs, by not paying for things using the details of an account where you have all your money. Trying to protect against fraud while keeping all your money in the account is sort of like carrying around thousands of dollars in cash in your wallet and then worrying about how to defend against robbery. Yes, you can carry a weapon or hire a bodyguard, but it's probably simpler to just not carry that much money in the first place. You already mentioned one solution with your option #1, which is to just keep a small amount of money in a separate account and use that for online payments. Assuming you can easily transfer money in and out of this account via online banking, this effectively is what you say you want in your edit: you log in to your bank online, but rather than \"\"informing it\"\" you're about to make a payment, you just transfer money in. You'll probably have to keep a small amount of money in the account to keep it open, but if this is an important issue for you, that shouldn't be that big a deal. Another solution is a credit card. With a credit card, you simply make the payment online. In the US, if the merchant (or someone else stealing the info) makes fraudulent charges, the credit card company assumes the liability and the consumer suffers only the inconvenience of having to get a new card issued. I don't know what the UK laws are regarding credit vs. debit fraud, but some sites I found seem to suggest that credit cards have fraud protection in the UK as well. This is probably worth looking into if you are concerned about fraud.\"", "title": "" }, { "docid": "89161", "text": "\"You ask about the difference between credit and debit, but that may be because you're missing something important. Regardless of credit/debit, there is value in carrying two different cards associated with two different accounts. The reason is simply that because of loss, fraud, or your own mismanagement, or even the bank's technical error, any card can become unusable for some period of time. Exactly how long depends what happened, but just sending you a new card can easily take more than one business day, which might well be longer than you'd like to go without access to any funds. In that situation you would be glad of a credit card, and you would equally be glad of a second debit card on a separate account. So if your question is \"\"I have one bank account with one debit card, and the only options I'm willing to contemplate are (a) do nothing or (b) take a credit card as well\"\", then the answer is yes, take a credit card as well, regardless of the pros or cons of credit vs debit. Even if you only use the credit card in the event that you drop your debit card down a drain. So what you can now consider is the pros and cons of a credit card vs managing an additional bank account -- unless you seriously hate one or more of the cons of credit cards, the credit card is likely to win. My bank has given me a debit card on a cash savings account, which is a little scary, but would cover most emergencies if I didn't have a credit card too. Of course the interest rate is rubbish and I sometimes empty my savings account into a better investment, so I don't use it as backup, but I could. Your final question \"\"can a merchant know if I give him number of debit or credit card\"\" is already asked: Can merchants tell the difference between a credit card and embossed debit card? Yes they can, and yes there are a few things you can't (or might prefer not to) do with debit. The same could even be said of Visa vs. Mastercard, leading to the conclusion that if you have a Visa debit you should look for a Mastercard credit. But that seems to be less of an issue as time goes on and almost everywhere in Europe apparently takes both or neither. If you travel a lot outside the EU then you might want to be loaded down with every card under the sun, and three different kinds of cash, but you'd already know that without asking ;-)\"", "title": "" }, { "docid": "481648", "text": "For me, it is mostly for the fraud protection. If I have a debit card and someone makes a fraudulent charge the money is removed from my bank account. From my understanding, I can then file a fraud complaint with the bank to recover my money. However, for some period of time, the money is missing from my bank account. I've heard conflicting stories of money being returned quickly while the complaint is undergoing investigation as well as money being tied up for several days/weeks. It may depend on the bank. With a credit card, it is the banks money that is tied up.", "title": "" }, { "docid": "571875", "text": "It is totally legal but it just has to be reported like income. Granted the IRS will probably not catch it. I work for a large company I get little gift cards all the time and they add the dollar value as income for taxes on my paycheck. It is a little annoying because I think it is kind of shit that a dollar value of a gift card is treated as the same value as real money, but they are amazon gift cards so better than cash to me.", "title": "" }, { "docid": "540325", "text": "You need to report the interest expense, assuming the loans were for your business: You need to report interest expense (only interest, principle is not an expense just as the loan proceeds are not income). The interest expense goes to the appropriate line on your Schedule C or E (depending on whether you used the loan for the online business or the rental). People whom you borrowed from must also report the interest as income to them on their Schedule B. You cannot deduct the interest expense if they don't report it as interest income. If you didn't take the loans for your business then the interest is not deductible. You don't need to report anything. People who lent you money still have to report the interest you paid to them as income on Schedule B. If you paid no interest (free loan) or below/above market interest to a related party (family member), then the imputed interest is considered income to them and gift to you. They need to report it on their Schedule B, and depending on amounts - on a gift tax return. For $1K to $10K loans there probably will be no need in gift tax returns, the exemption is for $14K per year per person. If the imputed interest rules may apply to you, better talk to a licensed tax adviser on how to proceed.", "title": "" }, { "docid": "480664", "text": "\"There are Cyber Security and Reporting Standards which Financial Service Provider (Banks and Financial services where customers deposit and/or transact fiat currency) You can find a comprehensive list on Wikipedia under Cyber security standards Depending on the geographic location there might be local Govt requirements such as reporting issues, data security etc. Concerning point 1. We have to differ between a fraudulent customer and an attacker on the banks infrastructure. Fraudulent customers / customers that have been compromised by third parties are identified with but not limited to credit scores and merchant databases or data from firms specialized in \"\"Fraud Prevention\"\". Attackers (Criminals that intend to steal, manipulate or spy on data) are identified/prevented/recorded by but not limited to IDS solutions and attacker databases. For firms that get compensation by insurances the most important thing is the compilant with law and have records of everything, they rather focus on recording data to backtrack attackers than preventing attacks. Concerning point 2. For you as customer the local law and deposit insurance are the most important things. Banks are insured and usually compensate customers on money theft. The authentication and PIN / TAN methods are most crucial but standard - these authentication methods consist of one password and one offline part such as a TAN from a paperletter or a RSA generator or card reader. WRAPUP: Financial institutions have to comply with local law and meet international standards. Banks use highly advanced Intrusion detection and fraud prevention which logically must be based on databases. For the average joe customer there is seldom high risk to lose deposits even if the attackers gains full access to the bank account but this depends a lot on the country you reside in. Concerning targeted attacks:\"", "title": "" }, { "docid": "353615", "text": "It depends on: In Canada, Ontario, Manitoba, Alberta and Nova Scotia have each enacted legislation to stop gift cards/certificates from expiring. Cards issued before the effective date are still subject to the old rules. The legislation came into effect: There are several common themes: There are still some unusual exemptions such as mall gift cards in Ontario, Manitoba: Ontario is the first jurisdiction in Canada to regulate gift cards. [...] Mall cards (e.g. Eaton Centre gift card) will be covered by the expiry date ban and the new disclosure rules. However, these cards can temporarily maintain their current fee structure while the provincial government examines options on how to best regulate these types of cards. This will allow more time to develop an approach that strikes the right balance for consumers and businesses. For specific details see the appropriate link.", "title": "" }, { "docid": "89403", "text": "Apparently it is up to the credit card company on how they want to report your available balance. Another disadvantage to the no-limit credit card may not be apparent to most people, but it is something noted by organizations like The Motley Fool, which is expert in many issues of finance and investment. Part of your credit score, about 30%, considers the amount of money you have borrowed, and the limit on your present credit cards. A no-limit credit card company may report your limit as $0 if you have not used the card, or they may report a maximum limit available to you. They may not, nor are they obligated, to report times when you put tons of expenses on a credit card and then paid them off. While some companies will report your timely payments and paid off amounts, others simply report an extremely low limit. For instance if you spent $100 US Dollars (USD), your limit might be considered $100 USD, or it may merely be reported as zero. You’ll need to check with a credit card company on how they report payments and limits on a no-limit credit card before you obtain one. Some people who are scrupulous are paying off their cards at the end of each month suffer major losses to their credit score, without even realizing it, if their spending ability is rated at zero, or their payments don’t count toward showing credit worthiness. Source", "title": "" }, { "docid": "450547", "text": "\"Leaving the issue of purchasing gift cards aside, xeroxing the coupons and reusing them is fraud. Your statement that \"\"well Target should have made unique coupon codes, they have more knowledge so it's on them\"\" opens a very dangerous path. If someone makes copies of dollar bills (but generates new, fake serial numbers since those are unique) it shouldn't be fraud because the government should have known better? If you read the actual thread (plus it's mentioned in the article) there are discussions of timing \"\"raids\"\" to catch cashier shift changes, people going from Target to Target, people wearing disguises, etc. How is that not clearly people knowing that what they were doing was fraudulent?\"", "title": "" }, { "docid": "277964", "text": "Like email and spam, fighting creditcard fraud is a cat and mouse game, with technology and processes constantly being developed to reduce fraud. The CVV on the back of the card is just one more layer of security. Requiring the CVV generally requires you to physically have access to the card. CVV should not be stored by any merchant. This frustrates card skimming fraud as the CVV is not present in the track data and fraud caused by database compromises. You should never use your PIN online. MC/VISA both have implementations of 3D-Secure (SecureCode for MC and Verified by VISA) which require a password / code to confirm card ownership. Depends on both Issuer and Merchant implementing the standard. Regarding not needing a PIN at the airport, some low value transactions no longer need PINs, depending on the Issuer and Scheme (VISA/MC). MasterCard PayPass or VISA PayWave enable low value contactless transactions without PIN. In Australia, the maximum value for a contactless transactions is $100 AUD. At some merchants (McDonalds for example) a PIN is not required for for meals purchased with VISA (at least, for the cheeseburger I bought there as a test). This makes sense - if you don't need a PIN for a contactless purchase, why do you need it for a chip based purchase? So - why allow PIN free transactions? On average customers report stolen credit cards / wallet very quickly and the losses are correspondingly small. As card issuers are always online, cards can be cancelled very quickly after being reported lost / stolen. Finally, by performing transactions for just a few cents or pennies, the merchant (Spotify) can likely validate you are the owner of the card as you'd need access to your online bank to confirm the transactions. PayPal do this with bank account to confirm ownership. (Unless I've misunderstood your statement).", "title": "" }, { "docid": "345697", "text": "\"It all comes down to how the loan itself is structured and reported - the exact details of how they run the loan paperwork, and how/if they report the activity on the loan to one of the credit bureaus (and which one they report to). It can go generally one of three ways: A) The loan company reports the status to a credit reporting agency on behalf of both the initiating borrower and the cosigner. In this scenario, both individuals get a new account on their credit report. Initially this will generally drop related credit scores somewhat (it's a \"\"hard pull\"\", new account with zero history, and increased debt), but over time this can have a positive effect on both people's credit rating. This is the typical scenario one might logically expect to be the norm, and it effects both parties credit just as if they were a sole signor for the loan. And as always, if the loan is not paid properly it will negatively effect both people's credit, and the owner of the loan can choose to come after either or both parties in whatever order they want. B) The loan company just runs the loan with one person, and only reports to a credit agency on one of you (probably the co-signor), leaving the other as just a backup. If you aren't paying close attention they may even arrange it where the initial party wanting to take the loan isn't even on most of the paperwork. This let the person trying to run the loan get something accepted that might not have been otherwise, or save some time, or was just an error. In this case it will have no effect on Person A's credit. We've had a number of question like this, and this isn't really a rare occurrence. Never assume people selling you things are necessarily accurate or honest - always verify. C) The loan company just doesn't report the loan at all to a credit agency, or does so incorrectly. They are under no obligation to report to credit agencies, it's strictly up to them. If you don't pay then they can report it as something \"\"in collections\"\". This isn't the typical way of doing business for most places, but some businesses still operate this way, including some places that advertise how doing business with them (paying them grossly inflated interest rates) will \"\"help build your credit\"\". Most advertising fraud goes unpunished. Note: Under all of the above scenarios, the loan can only effect the credit rating attached to the bureau it is reported to. If the loan is reported to Equifax, it will not help you with a TransUnion or Experian rating at all. Some loans report to multiple credit bureaus, but many don't bother, and credit bureaus don't automatically copy each other. It's important to remember that there isn't so much a thing as a singular \"\"consumer credit rating\"\", as there are \"\"consumer credit ratings\"\" - 3 of them, for most purposes, and they can vary widely depending on your reported histories. Also, if it is only a short-term loan of 3-6 months then it is unlikely to have a powerful impact on anyone's credit rating. Credit scores are formulas calibrated to care about long-term behavior, where 3 years of perfect credit history is still considered a short period of time and you will be deemed to have a significant risk of default without more data. So don't expect to qualify for a prime-rate mortgage because of a car loan that was paid off in a few months; it might be enough to give you a score if you don't have one, but don't expect much more. As always, please remember that taking out a loan just to improve credit is almost always a terrible idea. Unless you have a very specific reason with a carefully researched and well-vetted plan that means that it's very important you build credit in this specific way, you should generally focus on establishing credit in ways that don't actually cost you any money at all. Look for no fee credit cards that you pay in full each month, even if you have to start with credit-building secured card plans, and switch to cash-value no-fee rewards cards for a 1-3% if you operate your financial life in a way that this doesn't end up manipulating your purchasing decisions to cost you money. Words to the wise: \"\"Don't let the credit score tail wag the personal financial dog!\"\"\"", "title": "" }, { "docid": "277477", "text": "The details of credit score calculation tend to change periodically, but the fundamentals are mostly consistent. Pay your bills, keep your average account age high, overpay your credit card minimums, and keep your overall debt low. And do soft pulls on your credit report to see what's happening. First, the simplest route: pay all your bills early or on time. Automatic deduction may be useful in this regard, especially for bills with predictable amounts. A corollary to this tip is to never leave an unpaid bill. What often happens to young people is in the course of moving around they leave the final bill unpaid and it gets reported to collections. Make sure you follow up online with all bills, even after canceling the service. Second, average account age and oldest account age matter. Open an account like a credit card and never close it, so you'll have an older account (hopefully a zero-fee card). Try to keep other accounts open rather than closing them (no need to cancel a zero-fee credit card) so your average account age stays higher. A card that works on internal systems (like a gift card) is not going to show up on a credit report; a card that works like any VISA/MC is likely going to show up. The rule of thumb is if they need your SSN to run a credit check for the application, then the card will appear on a credit report. You can pull your credit report to find out if the card is listed (you may have to allow time for lag before the card appears, but I'm not sure how long that might be). Third, a tip for extra credit score is to pay more than the minimum required on credit card bills. You can achieve this by either using your credit card at least once a month or by leaving a small hanging balance each month so there's always something to overpay next month. Credit card reporting will be either: unpaid, underpaid, minimum paid, or overpaid. Minimum payment helps your score and overpayment helps more. If you can use your credit card every month, that will give you something to overpay every month. Otherwise, you can leave a small debt left on the card but still pay over the monthly minimum. However, your total debt load, especially debt carried on your cards, counts against your score; aim for less than 10% of your limit. Finally, of course, is to pull your credit report periodically. You need to know what others are seeing. Since debt load utilization matters, make sure the reported card maximum is correct on your credit report. Talk to your bank or account issuer if the limit is wrong. If a collection appears, then you need to handle it. Often you can negotiate with the collector, but be careful to negotiate how they will report the resolution. You want them to agree to remove any negative information (either in exchange for payment or because of a mistake). Failing that, you want them to mark it paid in full or satisfied in full; letting them notate your score that you only partially paid is what you want to avoid, since it most signals someone with cash flow problems and credit issues. They control their reporting to credit bureaus, so if the person on the phone demurs, ask to speak to their supervisor or someone with negotiating authority. Try to get any agreements in writing. Remember that your total debt load is a factor in your credit score. Home loans and student loans do affect credit score. If you take on a smaller home loan, then it will affect your credit less harshly (and leave you with smaller monthly payments).", "title": "" }, { "docid": "57229", "text": "Your clients should not send you 1099-MISC if they paid with a credit card. You can refer them to this text in the instructions for the form 1099-MISC: Payments made with a credit card or payment card and certain other types of payments, including third party network transactions, must be reported on Form 1099-K by the payment settlement entity under section 6050W and are not subject to reporting on Form 1099-MISC. See the separate Instructions for Form 1099-K. By sending out the 1099-MISC, your clients are essentially saying that they paid you directly (check or cash) in addition to the payment they made with a credit card (which will be reported on 1099-K). In case of an audit, you'll have trouble convincing the IRS that it didn't happen. I suggest asking the clients not to do this to you, since it may cost you significant amounts to fight the IRS later on. In any case, you report on your tax return what you really got, not what the 1099 says. If you have two 1099's covering the same income - there's no legal obligation to report the income twice. You do not have to pay twice the tax just because you have stupid clients. But you may have troubles explaining it to the IRS, especially if you're dealing with cash in your business. If you want to avoid matching issues, consider reporting all the 1099s, and then subtracting the duplicates and attaching a statement (the software will do it automatically when you add the description in the miscellaneous item) about what it is.", "title": "" }, { "docid": "571567", "text": "I think that a prepaid card would have more risk for loss than a traditional credit card. I've had a various credit cards for about the last 20 years. In all that time, I haven't lost a penny due to fraud. Of course, I've had some fraudulent charges show up, I've had merchants charge too much, and I've had my card number stolen. In every case, my bank has been able to undo any damage and issue me a new card number, if necessary. I really don't spend any time worrying about credit card security, other than checking my statement each month. Security is the bank's problem, not mine. Prepaid cards are often anonymous. If you are using an anonymous card, how can the bank verify that you are the owner of the card and that you did not make a certain charge? I think, with this type of card, you are very much at risk for losing whatever you have loaded on the card to fraudulent charges.", "title": "" }, { "docid": "183660", "text": "I've had a card cloned 15 years ago and used to buy over 5k of goods in another country. So the inconvenience of having a card closed and re-issued is quite annoying even though the charges were reversed and I was made whole. But these days most CC fraud isn't from a card scanned by a waiter and cloned then used elsewhere. Mostly it is poorly secured databases or point of sale terminal malware. The latter is getting curtailed by chipped cards and the largest source of fraud is now online transactions (so called card not present) where the merchant has your CC number. If their system is breached the bad guys have a wealth of card numbers they sell in an E-bay like site on the dark web. This is where the Citi virtual CC comes in handy. Here's how it works to protect the bank and the hassles you go through when a card as to be re-issued. Citi's virtual CCs let you generate an actual credit card, complete with security code and expiration date. What is unique is that once the virtual CC is used it can only be used subsequently by that same merchant and is declined by any other. You can also set a total limit on what the merchant can charge as well as an expiration date. I use them for all my online accounts because they are, for all practical purposes, immune to the malware that steals CC info. Even if somehow the virtual CC is used before the merchant makes the initial charge that locks in the CC to their account the charge can be reversed without closing your actual card which has a different number. You can manage multiple Citi virtual CCs and view charge status, close, or adjust limits over time so managing them is quite easy with no risk to your primary account.", "title": "" }, { "docid": "574060", "text": "\"Context: My parents overseas (Japan) sent me a little over $100,000 to cover an expensive tuition payment and moderate living expenses in 2014. They are not US residents, Green card holders or citizens. They did not remit the tuition payment directly to the school. I am a resident (for tax). This is enough to answer yes. That's basically the set of requirements for filing: you received >$100K from a non-US person and you yourself are a US person. You have to report it, and unless it is taxable income - it is a gift. Taxable income is reported on the form 1040, gifts are reported on the form 3520. The fact that in Japan it is not considered a gift is irrelevant. Gift tax laws vary between countries, some (many) don't have gift taxes at all. But the reporting requirement is based on the US law and the US definition of \"\"gift\"\". As I said above, if it is not a gift per the US law, then it is taxable income (and then you report all of it regardless of the amount and pay taxes). Had they paid directly to the institution, you wouldn't need to count it as income/gift to you because you didn't actually receive the money (so no income) and it went directly to cover your qualified education expenses (so no gift), but this is not the case in your situation. Whether or not this will be reported by the IRS back to Japan - I don't know, but it was probably already reported to the authorities in Japan by the banks through which the transfers went through. As to whether it will trigger an audit - doesn't really matter. It was, most likely, reported to the IRS already by the receiving banks in the US, so not reporting it on your tax return (either as income or on form 3520) may indeed raise some flags.\"", "title": "" }, { "docid": "13656", "text": "The first thing I assess when looking at new credit cards is whether it has no annual fee, the second thing I look at is how long the interest free period is. I always pay my credit card off in full just before the due date. Any rewards program is a bonus. My main credit card is with CBA, I have a credit limit of $20K and pay no annual fee. I get a bonus point for every $ I spend on it, for which I exchange for store gift cards to help with my everyday spending. Approximately 3500 point would get me a $25 gift card. But my main reward with the card is the interest I save by keeping my own money in a Home Loan Offset account whilst I spend with the Bank's money. Then I pay the full amount off by the due date so I do not pay any interest on the credit card. I only use my credit cards for purchases I would usually make anyway and to pay bills, so my spending would be the same with or without a credit card. I can usually save over $500 each year off my Home Loan interest and get about $350 worth of gift cards each year. If I didn't have any Home Loans then I would keep my money in a high interest depost account so I would be increasing my interest payments each year. Sure you can probably get credit cards with more generous rewards programs, but how much are you paying each year in annual fees, and if you don't have an interest free period and you don't pay off all the amount due each month how much are you paying in interest on the card? This is what you need to way up when looking at rewards programs on offer. Nothing is for free, well almost nothing !", "title": "" } ]
9522	Should I take out a bigger mortgage, or pay a greater cash deposit?	[ { "docid": "587358", "text": "The answer to your question depends on your answer to this question: Would you be willing to take out a loan at that interest rate and invest that money straight into stocks? That's basically what you're planning to do. You leverage your stock investment, which is a valid and often used way to improve returns. Better returns ALWAYS come with more risk. Depending on your location there might be a tax advantage to a mortage, which you can take into account.", "title": "" }, { "docid": "215149", "text": "At a minimum, I would save 20-30k, because you need to have both a safety net and some money for home repairs. Very few people move into a house and then do zero repairs - painting, usually, at a minimum, and there's almost always something that comes up pretty soon after. Even if you're buying a condo, you'll want to be sure you can fix anything that needs fixing within that first year or two. Beyond that, you have to decide based on your risk tolerance and your other details, like your income. Taking a smaller mortgage means a guaranteed 3% to 4% return, right now. That's not quite what you'll probably get on the market over the long term, but how did your investments do last year? My 401(k) was down slightly... In order to do better than that 3-4%, you're going to have to invest in stocks (or ETFs or similar), meaning you could have 10+% swings potentially year over year, which if that's your only (extra) 50k might be more than you can tolerate. If you're very risk tolerant and mostly looking to make money over the long term, then it may be worth it to you. But if a larger mortgage makes it harder to pay the monthly payments (a meaningfully smaller buffer), or if your job is such that you might end up having to sell those investments at a loss to cover your mortgage for a few months because you (didn't make enough\|got laid off\|etc.), then you may want the smaller mortgage to make that less of a risk (though still setting aside the safety net in something minimally risky).", "title": "" } ]	[ { "docid": "322825", "text": "\"Here in the UK, the rule of thumb is to keep a lot of equity in your home if you can. I assume here that you have a lot of savings you're considering using. If you only have say 10% of the house price you wouldn't actually have a lot of choice in the matter, the mortgage lender will penalise you heavily for low deposits. The practical minimum is 5%, but for most people a 95% mortgage is just silly (albeit not as silly as the 100% or greater mortgages you could get pre-2008), and you should take serious individual advice before considering it. According to Which, the average in the UK for first-time buyers is 20% (not the best source for that data I confess, but a convenient one). Above 20% is not at all unusual. You'll do an affordability calculation to figure out how much you can borrow, which isn't at all the same as how much you should borrow, but does get you started. Basically you, decide how much a month you can spend on mortgage payments. The calculation will let you put every penny into this if you choose to, but in practice you'll want some discretionary income so don't do that. decide the term of the mortgage. For a young first-time buyer in the UK I think you'd typically take a 25-year term and consider early repayment options rather than committing to a shorter term, but you don't have to. Mortgage lenders will offer shorter terms as long as you can afford the payments. decide how much you're putting into a deposit make subtractions for cost of moving (stamp duty if applicable, fees, removals aka \"\"people to lug your stuff\"\"). receive back a number which is the house price you can pay under these constraints (and of course a breakdown of what the mortgage principle would be, and the interest rate you'll pay). This step requires access to lender information, since their rates depend on personal details, deposit percentage, phase of the moon, etc. Our mortgage advisor did multiple runs of the calculation for us for different scenarios, since we hadn't made up our minds entirely. Since you have not yet decided how much deposit to make, you can use multiple calculations to see the effect of different deposits you might make, up to a limit of your total savings. Putting up more deposit both increases the amount you can borrow for a given monthly payment (since mortgage rates are lower when the loan is a lower proportion of house value), and of course increases the house price you can afford. So unless you're getting a very high return on your savings, £1 of deposit gets you somewhat more than £1 of house, and the calculation will tell you how much more. Once you've chosen the house you want, the matter is even simpler: do you prefer to put your savings in the house and borrow less and make lower payments, or prefer to put your savings elsewhere and borrow more and make higher payments but perhaps have some additional income from the savings. Assuming you maintain a contingency fund, a lower mortgage is generally considered a good investment in the UK, but you need to check what's right for you and compare it to other investments you could make. The issue is complicated by the fact that residential property prices are rising quite quickly in most areas of the UK, and have been for a long time, meaning that highly-leveraged property investment appears to be a really good idea. This leads to the imprudent, but tempting, conclusion that you should buy the biggest house you can possibly afford and watch its value rises. I do not endorse this advice personally, but it's certainly true that in a sharply rising house market it's easier to get away with buying a bigger house than you need, than it is to get away with it in a flat or falling market. As Stephen says, an offset mortgage is a no-brainer good idea if the rate is the same. Unfortunately in the UK, the rate isn't the same (or anyway, it wasn't a couple of years ago). Offset mortgages are especially good for those who make a lot of savings from income and for any reason don't want to commit all of those savings to a traditional mortgage payment. Good reasons for not wanting to do that include uncertainty about your future income and a desire to have the flexibility to actually spend some of it if you fancy :-)\"", "title": "" }, { "docid": "92038", "text": "\"When you compare the costs of paying your current mortgage with the rental income from the flat, you're not really comparing like with like. Firstly, the mortgage payments are covering both interest and capital repayments, so some of the 8k is money that is adding to your net worth. Secondly, the value of the flat (130k) is much more than the outstanding mortgage (80k) so if you did sell the flat and pay off the mortgage, you'd have 50k left in cash that could be invested to provide an income. The right way to compare the two options is to look at the different costs in each scenario. Let's assume the bigger house will cost 425k as it makes the figures work out nicely. If you buy the bigger house with a bigger mortgage, you will need to borrow 50k more so will end up with a mortgage of 130k, and you will still have the 8k/year from the flat. Depending on your other income, you might have to pay tax on the 8k/year - e.g. at 40% if you're a higher-rate taxpayer, leaving you with 4.8k/year. If you sell the flat, you'll have no mortgage repayments to make and no income from the flat. You'll be able to exactly buy the new house outright with the 50k left over after you repay the mortgage, on top of your old house. You'd also have to pay some costs to sell the flat that you wouldn't have to with the bigger mortgage, but you'd save on the costs of getting a new mortgage. They probably aren't the same, but let's simplify and assume they are. If anything the costs of selling the flat are likely to be higher than the mortgage costs. Viewed like that, you should look at the actual costs to you of having a 130k mortgage, and how much of that would be interest. Given that you'll be remortgaging, at current mortgage rates, I'd expect interest would only be 2-3%, i.e around 2.5k - 4k, so significantly less than the income from the flat even after tax. The total payment would be more because of capital repayment, but you could easily afford the cashflow difference. You can vary the term of the mortgage to control how much the capital repayment is, and you should easily be able to get a 130k mortgage on a 425k house with a very good deal. So if your figure of 8k rent is accurate (considering void periods, costs of upkeep etc), then I think it easily makes sense to get the bigger house with the bigger mortgage. Given the tax impact (which was pointed out in a comment), a third strategy may be even better: keep the flat, but take out a mortgage on it in exchange for a reduced mortgage on your main house. The reason for doing it that way is that you get some tax relief on the mortgage costs on an investment property as long as the income from that property is higher than the costs, whereas you don't on your primary residence. The tax relief used to just be at the same tax rate you were paying on the rental income, i.e. you could subtract the mortgage costs from the rental income when calculating tax. It's gradually being reduced so it's just basic rate tax relief (20%) even if you pay higher-rate tax, but it still could save you some money. You'd need to look at the different mortgage costs carefully, as \"\"buy-to-let\"\" mortgages often have higher interest rates.\"", "title": "" }, { "docid": "583918", "text": "\"Ultimately you are as stuck as all other investors with low returns which get taxed. However there are a few possible mitigations. You can put up to 15k p.a. into a \"\"normal\"\" ISA (either cash or stocks & shares, or a combination) if your target is to generate the depost over 5 years you should maximise the amount you put in an ISA. Then when you come to buy, you cash in that part needed to top up your other savings for a deposit - i.e. keep the rest in for long term savings. The help to buy ISA might be helpful, but yes there is a limit on the purchase price which in London will restrict you. Several banks are offering good interest on limited sums in current accounts - Santander is probably the best you can get 3% (taxed) on up to 20K - this is a good \"\"safe\"\" return. Just open a 123 Account, arrange to pay out a couple of DDs and pay in £500 a month (you can take the £500 straight out again). I think Lloyds and TSB also offer similar but on much smaller ammounts. Be warned this strategy taken to the limit will involve some complexity checking your various accounts each month. After that you will end up trading better returns for greater risk by using more volatile stock market investments rather than cash deposits.\"", "title": "" }, { "docid": "271110", "text": "\"To add to what other have stated, I recently just decided to purchase a home over renting some more, and I'll throw in some of my thoughts about my decision to buy. I closed a couple of weeks ago. Note that I live in Texas, and that I'm not knowledgeable in real estate other than what I learned from my experiences in the area when I am located. It depends on the market and location. You have to compare what renting will get you for the money vs what buying will get you. For me, buying seemed like a better deal overall when just comparing monthly payments. This is including insurance and taxes. You will need to stay at a house that you buy for at least 5-7 years. You first couple years of payments will go almost entirely towards interest. It takes a while to build up equity. If you can pay more towards a mortgage, do it. You need to have money in the bank already to close. The minimum down payment (at least in my area) is 3.5% for an FHA loan. If you put 20% down, you don't need to pay mortgage insurance, which is essentially throwing money away. You will also have add in closing costs. I ended up purchasing a new construction. My monthly payment went up from $1200 to $1600 (after taxes, insurance, etc.), but the house is bigger, newer, more energy efficient, much closer to my work, in a more expensive area, and in a market that is expected to go up in value. I had all of my closing costs (except for the deposit) taken care of by the lender and builder, so all of my closing costs I paid out of pocket went to the deposit (equity, or the \"\"bank\"\"). If I decide to move and need to sell, then I will get a lot (losing some to selling costs and interest) of the money I have put in to the house back out of it when I do sell, and I have the option to put that money towards another house. To sum it all up, I'm not paying a difference in monthly costs because I bought a house. I had my closing costs taking care of and just had to pay the deposit, which goes to equity. I will have to do maintenance myself, but I don't mind fixing what I can fix, and I have a builder's warranties on most things in the house. To really get a good idea of whether you should rent or buy, you need to talk to a Realtor and compare actual costs. It will be more expensive in the short term, but should save you money in the long term.\"", "title": "" }, { "docid": "163216", "text": "\"In the US, the title company usually collects all money being paid by parties to the sale (including the buyer, seller, and mortgage companies) and then pays out money where its due to the respective parties (the seller, and possibly mortgage companies, housing inspectors, etc.) If you have equity, meaning that you sold your house for a price greater than what you owed on your mortgage, you'll typically get them money from the title company, but they are really passing through money that they got from the buyer (less whatever fees are going to the title company itself and other third parties involved). One misconception, however, is that if you paid off part of your mortgage over time that you automatically \"\"have equity.\"\" That's really only true if you find a buyer willing to pay a price greater than what's left on your mortgage. When housing prices decline, it's possible that you as the seller may need to bring a check to closing and do not get any money back. (They buyer is presumably bringing a bigger check, but you would need to make up the difference between what the buyer pays and what you still owe on your mortgage.)\"", "title": "" }, { "docid": "503171", "text": "Some large merchants do not give discounts for cash payments as this does not work out any cheaper for them, vs Credit Card payments. In Credit Card typically fees given to all the 3 parties (Merchant bank, Issuer Bank and Visa) would be around 3%. If cash payment is made, and the amounts are large (say at Walmart / K-Mart they have to deposit such cash at Banks, Have a provision to Storing Cash at Stores, People to count the cash. So essentially they will have to pay for Cash Officer to count, Bigger Safe to store, Transport & Security & Insurance to take Cash to Bank Plus Banks charge around 1% charge for counting the large cash being deposited. This cash would be in local branch where as the operations are centralized and Walmart/K-Mart would need the money in central account, it takes time to get it transferred to a central account, and there is a fee charged by Bank to do this automatically. On the other hand, smaller merchants would like cash as they are operated stand-alone and most of their purchases are also cash. Hence they would tend to give a discount for cash payment if any.", "title": "" }, { "docid": "278846", "text": "\"It sounds like you are isolated and in a small town. Without the true ability to bank, perhaps you should move. As an alternative you could do some kind of online banking. Most banks offer the ability to deposit via mobile phone and you could obtain cash by using remote ATMs or writing checks for an amount over your purchase at the grocery store. How are you paid? If via direct deposit, that makes mobile banking even easier. Did your read your premise out loud? Using Game Stop as a bank is just silly. Are you banned from banks because of not paying child support or some other legal obligation? If so just \"\"face the music\"\". I know people that are over 40 and owed a relatively small amount of child support and the result of they lost out on order of magnitudes greater income. It was just a short-sighted move that cost them far more than if they just obeyed the court order. It would be smarter to use a check cashing store, like AmScott, to do your banking. They will cash checks for a fee, issue money orders, or even allow you to pay some bills directly through them. Never, ever use them to cash a hot check or for short term financing but using them or Walmart, or the Grocery store is a much better option than Game Stop.\"", "title": "" }, { "docid": "93518", "text": "\"It may seem weird but interest rates are set by a market. Risk is a very large component of the price that a saver will accept to deposit their money in a bank but not the only one. Essentially you are \"\"lending\"\" deposited cash to the bank that you put it in and they will lend it out at a certain risk to themselves and a certain risk to you. By diversifying who they lend to (corporations, home-buyers each other etc.) the banks mitigate a lot of the risk but lending to the bank is still a risky endeavour for the \"\"saver\"\" and the saver accepts a given interest rate for the amount of risk there is in having the money in that particular bank. The bank is also unable to diversify away all possible risk, but tries to do the best job it can. If a bank is seen to take bigger risks and therefore be in greater risk of failing (having a run on deposits) it must have a requisitely higher interest rates on deposits compared to a lower risk bank. \"\"Savers\"\" therefore \"\"shop around\"\" for the best interest rate for a given level of risk which sets the viable interest rate for that bank; any higher and the bank would not make a profit on the money that it lends out and so would not be viable as a business, any lower and savers would not deposit their money as the risk would be too high for the reward. Hence competition (or lack of it) will set the rate as a trade off between risk and return. Note that governments are also customers of the banking industry when they are issuing fixed income securities (bonds) and a good deal of the lending done by any bank is to various governments so the price that they borrow money at is a key determinant of what interest rate the bank can afford to give and are part of the competitive banking industry whether they want to be or not. Since governments in most (westernised) countries provide insurance for deposits the basic level of (perceived) risk for all of the banks in any given country is about the same. That these banks lend to each other on an incredibly regular basis (look into the overnight or repo money market if you want to see exactly how much, the rates that these banks pay to and receive from each other are governed by interbank lending rates called Libor and Euribor and are even more complicated than this answer) simply compounds this effect because it makes all of the banks reliant on each other and therefore they help each other to stay liquid (to some extent). Note that I haven't mentioned currency at all so far but this market in every country applies over a number of currencies. The way that this occurs is due to arbitrage; if I can put foreign money into a bank in a country at a rate that is higher than the rate in its native country after exchange costs and exchange rate risk I will convert all of my money to that currency and take the higher interest rate. For an ordinary individual's savings that is not really possible but remember that the large multinational banks can do exactly the same thing with billions of dollars of deposits and effectively get free money. This means that either the bank's interest rate will fall to a risk adjusted level or the exchange rate will move. Either of those moves will remove the potential for making money for nothing. In this case, therefore it is both the exchange rate risk (and costs) as well as the loan market in that country that set the interest rate in foreign currencies. Demand for loans in the foreign currency is not a major mover for the same reason. Companies importing from foreign entities need cash in foreign currencies to pay their bills and so will borrow money in other currencies to fulfil these operations which could come from deposits in the foreign currency if they were available at a lower interest rate than a loan in local currency plus the costs of exchange but the banks will be unwilling to loan to them for less than the highest return that they can get so will push up interest rates to their risk level in the same way that they did in the market before currencies were taken into account. Freedom of movement of foreign currencies, however, does move interest rates in foreign currencies as the banks want to be able to lend as much of currencies that are not freely deliverable as they can so will pay a premium for these currencies. Other political moves such as the government wanting to borrow large amounts of foreign currency etc. will also move the interest rate given for foreign currencies not just because loaning to the government is less risky but also because they sometimes pay a premium (in interest) for being able to borrow foreign currency which may balance this out. Speculation that a country may change its base interest rate will move short term rates, and can move long term rates if it is seen to be a part of a country's economic strategy. The theory behind this is deep and involved but the tl;dr answer would be the standard \"\"invisible hand\"\" response when anything market or arbitrage related is involved. references: I work in credit risk and got a colleague who is also a credit risk consultant and economist to look over it. Arbitrage theory and the repo markets are both fascinating so worth reading about!\"", "title": "" }, { "docid": "111580", "text": "\"The simplest argument for overpayment is this: Let's suppose your fixed rate mortgage has an interest rate of 4.00%. Every £1 you can afford to overpay gives you a guaranteed effective return of 4.00% gross. Yes your monthly mortgage payment will stay the same; however, the proportion of it that's paying off interest every month will be less, and the amount that's actually going into acquiring the bricks and mortar of your home will be greater. So in a sense your returns are \"\"inverted\"\" i.e. because every £1 you overpay is £1 you don't need to keep paying 4% a year to continue borrowing. In your case this return will be locked away for a few more years, until you can remortgage the property. However, compared to some other things you could do with your excess £1s, this is a very generous and safe return that is well above the average rate of UK inflation for the past ten years. Let's compare that to some other options for your extra £1s: Cash savings: The most competitive rate I can currently find for instant access is 1.63% from ICICI. If you are prepared to lock your money away until March 2020, Melton Mowbray Building Society has a fixed rate bond that will pay you 2.60% gross. On these accounts you pay income tax at your marginal rate on any interest received. For a basic rate taxpayer that's 20%. If you're a higher rate taxpayer that means 40% of this interest is deducted as tax. In other words: assuming you pay income tax at one of these rates, to get an effective return of 4.00% on cash savings you'd have to find an account paying: Cash ISAs: these accounts are tax sheltered, so the income tax equation isn't an issue. However, the best rate I can find on a 4 year fixed rate cash ISA is 2.35% from Leeds Building Society. As you can see, it's a long way below the returns you can get from overpaying. To find returns such as that you would have to take a lot more risk with your money – for example: Stock market investments: For example, an index fund tracking the FTSE 100 (UK-listed blue chip companies) could have given you a total return of 3.62% over the last 3 years (past performance does not equal future returns). Over a longer time period this return should be better – historical performance suggests somewhere between 5 to 6% is the norm. But take a closer look and you'll see that over the last six months of 2015 this fund had a negative return of 6.11%, i.e. for a time you'd have been losing money. How would you feel about that kind of volatility? In conclusion: I understand your frustration at having locked in to a long term fixed rate (effectively insuring against rates going up), then seeing rates stay low for longer than most commentators thought. However, overpaying your mortgage is one way you can turn this situation into a pretty good deal for yourself – a 4% guaranteed return is one that most cash savers would envy. In response to comments, I've uploaded a spreadsheet that I hope will make the numbers clearer. I've used an example of owing £100k over 25 years at an unvarying 4% interest, and shown the scenarios with and without making a £100/month voluntary overpayment, assuming your lender allows this. Here's the sheet: https://www.scribd.com/doc/294640994/Mortgage-Amortization-Sheet-Mortgage-Overpayment-Comparison After one year you have made £1,200 in overpayments. You now owe £1,222.25 less than if you hadn't overpaid. After five years you owe £6,629 less on your mortgage, having overpaid in £6,000 so far. Should you remortgage at this point that £629 is your return so far, and you also have £6k more equity in the property. If you keep going: After 65 months you are paying more capital than interest out of your monthly payment. This takes until 93 months without overpayments. In total, if you keep up £100/month overpayment, you pay £15,533 less interest overall, and end your mortgage six years early. You can play with the spreadsheet inputs to see the effect of different overpayment amounts. Hope this helps.\"", "title": "" }, { "docid": "131635", "text": "\"Like Dheer said, the demand for shorter term money is greater than for longer term money, precisely because the banks don't want to have to pay big interest rates for long periods. Banks borrow short term and lend long term - so they take money from you for one year, and lend it away as a 20 year mortgage. After a year, they take money for another year. Since short term rates tend to be higher than longer term rates, they make money off the \"\"spread\"\" (or the different between the rate they lend and the rate they borrow). In this scenario, banks should pay higher for longer term deposits, but overall banks realize that interest rates will go up and down, and they don't want to lock the \"\"up\"\" for a longer term. Since banks believe that rates will come down in the 1-2 year period, they offer good rates only till the 1 year period and disincentivize longer term deposits by offering lower rates. If you look at the interbank or money markets, trading of very short term bulk money shows that for the 10-15 day periods, the interest rates being offered are 10% or so, while for one year it's just 9.5%. The market believes that interest rates will go down in the one year time frame - but you never really know since this is just a bunch of people that believe so. Eventually, if rates continue to go up, the demand at the longer term will also go up, because it will become obvious that the rate pressure continues to be strong. If you do want higher rates for the long term, check out State bank of India bonds that are currently trading on the NSE (you can buy them if you have a brokerage account) They are just about as safe as SBI Fixed Deposits, and the rate being offered is around 9.3%, for a 10-15 year term. Hope that helps!\"", "title": "" }, { "docid": "249054", "text": "\"You have 1998-2011 income-contingent student loans, where the interest rate is the lower of (1% + base rate) or RPI (retail price inflation). For the next few years the it's likely to be (1% + base rate) as interest rates stay low and inflation shoots up. These loans only need to be repaid in proportion to your salary, and if they aren't repaid for long enough (e.g. the holder takes a career break for children) they are written off. So all-in-all, they are pretty good debt to have: low interest rate, and you might not have to repay them ever. It's likely that your mortgage will have a significantly higher rate than the student loan, so you'd be better off reducing your mortgage. Also, the higher deposit might mean you can get a lower interest rate on the whole mortgage because the lender will see you as a lower risk, so the return from \"\"investing\"\" it in your mortgage would be even greater than the raw interest rate. Having the student loan outstanding might make some difference to the \"\"affordability\"\" check for your mortgage payments, but lenders will be very familiar with how they work. Reducing your mortgage payments with the higher deposit should easily counterbalance that. Your own suggestion is to invest the £30K in a \"\"reasonably safe portfolio\"\" making 5%. There'll inevitably be some risk in that - 5% is a relatively high return in today's climate - but if you're willing to take that risk, you can investigate the effect on your mortgage to see if it's worth it or not.\"", "title": "" }, { "docid": "375877", "text": "There is really much simpler explanation for the interest rate differences in different countries. It is the interest rate arbitrage. It is a very well explored economic concept, so you can look it up on the Internet, in case you want to know more. 1) Interest rates for the same currency in different countries Basically, as one smart person here pointed out, there is only one price of money in free market economy. It happens, because investors can move their money unrestrictedly anywhere in the World to capitalize on the local interest rates advantage. For instance, if I can take a loan in the USA at 3-4% annual interest and receive 5-6% annual income on my dollar deposit in Russia, I would take a loan in the US and open a deposit in Russia to enjoy a risk free interest rate differential income of 2% (5-6% - 3-4% ~ 2%). So, would any reasonable person. However, in real World very few banks in Russia or anywhere would pay you an an interest rate higher than it can borrow money at. It'd probably lose money if it'd do so. Anyways, the difference between the risk free rate and interest rate on the dollar deposit can be attributed to the risk premium of this particular bank. The higher expected return, the greater risk premium. If there is a positive difference in the interest rates on the dollar deposits in different countries, it will almost entirely accounted for the risk premium. It is generally much riskier to keep money in, say Russian bank, than American. That's why investors want greater return on their dollar deposits in Russian banks than in American. Of course, if you'd want to park your USD in Russian bank you'd also have to consider transaction costs. So, as you may have already guessed, there is no free lunch. 2) Interest rates in different currencies for different countries If we are talking about the interest rates in different sovereign currencies, it is a somewhat similar concept, only there is more risk if you keep money in local currency (risk premium is much higher). Probably, the biggest component of this risk is inflation (that is only attributed to the prices in local currency). For that reason, current interest rates on deposits in Russian Rubles are at 10-12%, but only 1-3% in the US Dollars. An economic concept that discusses this phenomenon in great detail is Interest Rate Parity. Hope this was helpful. P.S. It doesn't look quite realistic that you can get an 8% annual income for USD deposit in Russia with the interest rates in the U.S. being at 1-2%. At present moment, a 30-year mortgage annual interest rate in the US is at ~2-3% and an annual interest rates for dollar deposits in Sberbank (one of the safest Russian banks = very little risk premium) is at 1-3%. So, arbitrage is impossible.", "title": "" }, { "docid": "386994", "text": "The main reason for paying your mortgage off quickly is to reduce risk should a crisis happen. If you don't have a house payment, you have much higher cash flow every month, and your day-to-day living expenses are much lower, so if an illness or job loss happens, you'll be in a much better position to handle it. You should have a good emergency fund in place before throwing extra money at the mortgage so that you can cover the bigger surprises that come along. There is the argument that paying off your mortgage ties up cash that could be used for other things, but you need to be honest with yourself: would you really invest that money at a high enough rate of return to make up your mortgage interest rate after taxes? Or would you spend it on other things? If you do invest it, how certain are you of that rate of return? Paying off the mortgage saves you your mortgage interest rate guaranteed. Finally, there is the more intangible aspect of what it feels like to be completely debt free with no payments whatsoever. That feeling can be a game-changer for people, and it can free you up to do things that you could never do when you're saddled with a mortgage payment every month.", "title": "" }, { "docid": "60981", "text": "So if I understand your plan right, this will be your situation after the house is bought: Total Debt: 645,000 Here's what I would do: Wait until your house sells before buying a new one. That way you can take the equity from that sale and apply it towards the down payment rather than taking a loan on your retirement account. If something happens and your house doesn't sell for as mush as you think it will, you'll lose out on the gains from the amount you borrow, which will more than offset the interest you are paying yourself. AT WORST, pay off the 401(k) loan the instant your sale closes. Take as much of the remaining equity as you can and start paying down student loans. There are several reasons why they are a higher priority than a mortgage - some are mathematical, some are not. Should I look to pay off student loans sooner (even if I refi at a lower rate of 3.5% or so), or the mortgage earlier ... My thoughts are that the student loans follow me for life, but I can always sell and buy another home So you want this baggage for the rest of your life? How liberating will it be when you get that off your back? How much investing are you missing out on because of student loan payments? What happens if you get lose your license? What if you become disabled? Student loans are not bankruptable, but you can always sell the asset behind a mortgage or car loan. They are worse than credit card debt in that sense. You have no tangible asset behind it and no option for forgiveness (unless you decide to practice in a high-need area, but I don't get the sense that that's your path). The difference in interest is generally only a few payment' worth over 15 years. Is the interest amortized the same as a 15 year if I pay a 30 year mortgage in 15 years? Yes, however the temptation to just pay it off over 30 years is still there. How often will you decide that a bigger car payment, or a vacation, or something else is more important? With a 15-year note you lock in a plan and stick to it. Some other options:", "title": "" }, { "docid": "107350", "text": "The common opinion is an oversimplification at best. The problem with buying a house using cash is that it may leave you cash-poor, forcing you to take out a home equity loan at some point... which may be at a higher rate than the mortgage would have been. On the other hand, knowing that you have no obligation to a lender is quite nice, and many folks prefer eliminating that source of stress. IF you can get a mortgage at a sufficiently low rate, using it to leverage an investment is not a bad strategy. Average historical return on the stock market is around 8%, so any mortgage rate lower than that is a relatively good bet and a rate MUCH lower (as now) is that much better a bet. There is, of course, some risk involved and the obligation to make mortgage payments, and your actual return is reduced by what you're paying on the mortage... but it's still a pretty good deal. As far as investment vehicles: The same answers apply as always. You want a rate of return higher than what you're paying on the mortgage, preferably market rate of return or better. CDs won't do it, as you've found. You're going to have to increase the risk to increase the return. That does mean picking and maintaining a diversified balance of investments and investment types. Working with index funds makes diversifying within a type easy, but you're probably going to want both stocks and bonds, rebalancing between them when they drift too far from your desired mix. My own investments are a specific mix with one each of bond fund, large cap fund, small cap fund, REIT, and international fund. Bonds are the biggest part of that, since they're lowest risk, but the others play a greater part in producing returns on the investments. The exact mix that would be optimal for you depends on your risk tolerance (I'm classified as a moderately aggressive investor), the time horizon you're looking at before you may be forced to pull money back out of the investments, and some matters of personal taste. I've been averaging about 10%, but I had the luxury of being able to ride out the depression and indeed invest during it. Against that, my mortgage is under 4% interest rate, and is for less than 80% of the purchase price so I didn't need to pay the surcharge for mortgage insurance. In fact, I borrowed only half the cost of the house and paid the rest in cash, specifically because leveraging does involve some risk and this was the level of risk I was comfortable with. I also set the duration of the loan so it will be paid off at about the same time I expect to retire. Again, that's very much a personal judgement. If you need specific advice, it's worth finding a financial counselor and having them help you run the numbers. Do NOT go with someone associated with an investment house; they're going to be biased toward whatever produces the most income for them. Select someone who is strictly an advisor; they may cost you a bit more but they're more likely to give you useful advice. Don't take my word for any of this. I know enough to know how little I know. But hopefully I've given you some insight into what the issues are and what questions you need to ask, and answer, before making your decisions.", "title": "" }, { "docid": "235055", "text": "\"> My issue understanding this is I've been told that banks actually don't hold 10% of the cash and lend the other 90% but instead hold the full 100% in cash and lend 900%. Is this accurate? That's the money multiplier effect being poorly described. You take a loan out, but that loan eventually makes its way to other banks as cash deposits, which then are loaned out, and go to other banks, and loaned, etc., so that the economy is \"\"running\"\" on 10x cash, where 1x is in physical cash, and the other 9x is in this deposit-loan-deposit phenomenon. > The issue I see with it is that it becomes exponential growth that is uncapped. Not true. If there is $1B outstanding \"\"physical\"\" cash (the money supply) with a 10% reserve, then the maximum amount of \"\"money\"\" flowing through is $1B / 10% = $10B. This assumes EVERYTHING legally possible is loaned out or saved in the banking system. As such, it represents a cap. If you have an Excel spreadsheet handy, you can easily model this out in four columns. Label the first row as follows: Deposit, Reserve, Cash Reserve, Loan Amount A2 will be your money supply. For simplicity, put $100. B2, your reserve column, will be 10%. C2 should be =A2 * B2, which will be the cash reserve in the bank. D2 should be A2 - C2, which is the new loan amount extended. A3 should be = D2, as the loans extended from the last step become deposits in the next. B3 = B2. Now, drag the formulas down, say, 500 rows. If you then sum the \"\"deposits\"\" column, it'll total $1,000. The cash reserve will total $100, and the loan amount will be $900. Thus, there is a cap.\"", "title": "" }, { "docid": "554087", "text": "What could a small guy with $100 do to make himself not poor To answer the question directly, not much. Short of investing in something at the exact moment before it goes bananas, then reinvesting into a bigger stock and bigger etc, it's super high risk. A better way is to sacrifice some small things, less coffee, less smokes, less going out partying so that instead of having $100, you have $100 a week. This puts you into a situation where you can save enough to become a deposit on an appreciating asset (choose your own asset class, property in AU for me). Take out a loan for as much as you can for your $100 a week payment and make it interest only with an offset against it, distributions from shares can either be reinvested or put into the offset or in the case of property, rent can be put against the offset, pretty soon you end up with a scenario where you have cash offsetting a loan down to nothing but you still have access to the cash, invest into another place and revalue your asset, you can take out any equity that has grown and put that also into your offset. Keep pulling equity and using the money from the offset as deposits on other assets (it kind of works really well on property) and within 15 years you can build an empire with a passive income to retire on. The biggest thing the rich guys get that the poor guys don't is that debt is GOOD, use someone else's money to buy an appreciating asset then when you pay it back eventually, you own the growth. Use debt to buy more debt for exponential growth. Of course, you need to also invest your time to research what you are investing in, you need to know when you make the decision to buy that it will appreciate, it's no good just buying off a tip, you may as well drop your money on the horses if you want to play it like that. Fortunately, one thing we all have in common regardless of our money is time, we have time which we can invest.", "title": "" }, { "docid": "585823", "text": "When discussing buying a home I often hear people say they like having a mortgage because they get the benefit of writing off the interest. I assume this is the United States. You need to also consider that many people can take the standard deduction of about $12k for married couples filing jointly, so even if they itemize the interest, it would only make sense to 'write it off' if you are able to itemize deductions greater than the standard deduction: Source: http://www.forbes.com/sites/kellyphillipserb/2013/10/31/irs-announces-2014-tax-brackets-standard-deduction-amounts-and-more/ So some people will input the mortgage interest and other related deductions into the computer only to find out that their itemized deductions don't add up. Where it benefits people sometimes is if they have medical bills which are greater than 10% of their income in addition to the mortgage interest. So it benefits them to itemize. There are other major sources of itemization but medical bills are very common. Other common items are auto registration taxes or interest from student loans. It is going to be situation dependent, but if you are within a few years of paying off the mortgage it would make sense to make micropayments to accelerate the payoff date. If you have 30 years to go, it would make more sense to generate an emergency fund, pay off a car, or save up for other things in life than worry about paying off a mortgage. Take the benefit of deducting the mortgage interest if you can, but I imagine that many people would be surprised to hear that it's not always black and white.", "title": "" }, { "docid": "554814", "text": "\"I don't follow the numbers in your example, but the fundamental question you're asking is, \"\"If I can borrow money for a low cost, and if I think I can invest it and receive returns greater than that cost, should I do it?\"\" It doesn't matter where that money comes from, a mortgage that's bigger than it needs to be, a credit card teaser rate, or a margin line from your stock broker. The answer is \"\"maybe\"\" - depending on the certainty you have about the returns you'd receive on your investments and your tolerance for risk. Only you can answer that question for yourself. If you make less than your mortgage rates on the investments, you'll wish you hadn't! As an aside, I don't know anything about Belgian tax law, but in US tax law, your deductions can be limited to the actual value of the home. Your law may be similar and thus increase the effective mortgage interest rate.\"", "title": "" }, { "docid": "40003", "text": "The cost to the store is small. They may have to pay a slightly greater fee because the transaction is now bigger. They do need additional cash on hand. Even though the majority of transactions are electronic (credit/debit) or check, the local grocery store still seems to have significant cash on hand. This is seen as a customer service. If there is a 2% fee the $50 advance costs them $1 for the minority of customers that take advantage of it. After more than 10 years of doing this they have figured this into the cost of groceries. Of course the credit card company could also waive the fee to store. My credit card online statement does tell me how much cash back was received. The line says date, store, amount ($40.00 cash over and $123.45 purchases) $163.45 total. Therefore the credit card company knows that cash back was used.", "title": "" }, { "docid": "503742", "text": "\"I have been a landlord in Texas for just over 3 years now. I still feel like a novice, but I will give you the benefit of my experience. If you are relying on rental properties for current income versus a long term return you are going to have to do a good job at shopping for bargains to get monthly cash flow versus equity growth that is locked up in the property until you sell it. If you want to pull a lot of cash out of a property on a regular basis you probably are going to have to get into flipping them, which is decidedly not passive investing. Also, it is easy to underestimate the expenses associated with rental properties. Texas is pretty landlord friendly legally, however it does have higher than usual property taxes, which will eat into your return. Also, you need to factor in maintenance, vacancy, tenant turnover costs, etc. It can add up to a lot more than you would expect. If you are handy and can do a lot of repairs yourself you can increase your return, but that makes it less of a passive investment. The two most common rules I have heard for initially evaluating whether an investment property is likely to be cash flow positive are the 1% and 50% rules. The 1% rule says the expected monthly rent needs to be 1% or greater of the purchase price of the house. So your hypothetical $150K/$10K scenario doesn't pass that test. Some people say this rule is 2% for new landlords, but in my experience you'd have to get lucky in Texas to find a house priced that competitively that didn't need a lot of work to get rents that high. The 50% rule says that the rent needs to be double your mortgage payment to account for expenses. You also have to factor in the hassle of dealing with tenants, the following are not going to happen when you own a mutual fund, but are almost inevitable if you are a landlord long enough: For whatever reason you have to go to court and evict a tenant. A tenant that probably lost their job, or had major medical issues. The nicest tenant you ever met with the cutest kids in the world that you are threatening to make homeless. Every fiber of your being wants to cut them some slack, but you have a mortgage to pay and can't set an expectation that paying the rent on time is a suggestion not a rule. or the tenant, who seemed nice at first, but now considers you \"\"the man\"\" decides to fight the eviction and won't move out. You have to go through a court process, then eventually get the Sheriff to come out and forcibly remove them from the property, which they are treating like crap because they are mad at you. All the while not paying rent or letting you re-let the place. The tenant isn't maintaining the lawn and the HOA is getting on your butt about it. Do you pay someone to mow the grass for them and then try to squeeze the money out of the tenant who \"\"never agreed to pay for that\"\"? You rent to a college kid who has never lived on their own and has adopted you as their new parent figure. \"\"The light in the closet went out, can you come replace the bulb?\"\" Tenants flat out lying to your face. \"\"Of course I don't have any pets that I didn't pay the deposit for!\"\" (Pics all over facebook of their kids playing with a dog in the \"\"pet-free\"\" house)\"", "title": "" }, { "docid": "6339", "text": "Should I use the profit to pay down student loans or just roll it into my next house in order to have a lower mortgage amount? Calculate the amount of interest in each scenario, where the two scenarios are: Use extra cash to pay down student loans, take out a full mortgage. Use extra cash to make a big down payment on the next house, keep paying down student loans at normal rate. In both scenarios the student loan rate will stay the same. However in the second scenario you may get a lower interest rate from making a larger down payment. So then calculate the total interest resulting from each scenario: student loan rateXremaining student loan balance=student loan interest new mortgage rateXnew mortgage balance=mortgage interest scenario 1 interest = student loan interest+mortgage interest student loan rateXstudent loan balance = student loan interest new mortgage rate with large down paymentXnew mortgage balance after large down payment = mortgage interest scenario 2 interest = student loan interest+mortgage interest Whichever scenario's interest is lower will save money.", "title": "" }, { "docid": "127601", "text": "Peace of mind is the key to your question. Just before the US housing bust of 2007, I had someone try to convince me to take all the equity from my house which was overvalued in an overheated market. The idea was to put that money in the stock market for a bigger return than the interest on the house. Many people did that and found themselves out of jobs as the economy crashed. Unfortunately, they couldn't sell their homes because they owed more than they were worth. I never lost a night of sleep over the money I didn't make in the stock market. I did manage to trade up to a house twice the size by buying another when the housing market bottomed out, but waiting for a market recovery to sell the smaller house. The outcome of my good fortune is a very nice house with no mortgage worth about 1/3 of my total net worth. That's probably a larger percentage than most money managers would recommend, but it is steadily decreasing because now, all the money that would go to a mortgage payment instead gets deposited in retirement accounts, and it still has 30 years to grow before I start drawing it down. I almost don't remember the burden of a mortgage hanging over my head each month. Almost.", "title": "" }, { "docid": "174308", "text": "\"I'll start by focussing on the numbers. I highly recommend you get comfortable with spreadsheets to do these calculations on your own. I assume a $200K loan, the mortgage for a $250K house. Scale this up or down as appropriate. For the rate, I used the current US average for the 30 and 15 year fixed loans. You can see 2 things. First, even with that lower rate to go 15 years, the payment required is 51% higher than with the 30. I'll get back to that. Second, to pay the 30 at 15 years, you'd need an extra $73. Because now you are paying at a 15 year pace, but with a 30 year rate. This is $876/yr to keep that flexibility. These are the numbers. There are 2 camps in viewing the longer term debt. There are those who view debt as evil, the $900/mo payment would keep them up at night until it's gone, and they would prefer to have zero debt regardless of the lifestyle choices they'd need to make or the alternative uses of that money. To them, it's not your house as long as you have a mortgage. (But they're ok with the local tax assessor having a statutory lien and his hand out every quarter.) The flip side are those who will say this is the cheapest money you'll ever see, and you should have as large a mortgage as you can, for as long as you can. Treat the interest like rent, and invest your money. My own view is more in the middle. Look at your situation. I'd prioritize In my opinion, it makes little sense to focus on the mortgage unless and until the first 5 items above are in place. The extra $459 to go to 15? If it's not stealing from those other items or making your cash flow tight, go for it. Keep one subtle point in mind, risk is like matter and energy, it's not created or destroyed but just moved around. Those who offer the cliche \"\"debt creates risk\"\" are correct, but the risk is not yours, it's the lender's. Looking at your own finances, liquidity is important. You can take the 15 year mortgage, and 10 years in, lose your job. The bank still wants its payments every month. Even if you had no mortgage, the tax collector is still there. To keep your risk low, you want a safety net that will cover you between jobs, illness, new babies being born, etc. I've gone head to head with people insisting on prioritizing the mortgage payoff ahead of the matched 401(k) deposit. Funny, they'd prefer to owe $75K less, while that $75K could have been deposited pretax (so $100K, for those in the 25% bracket) and matched, to $200K. Don't make that mistake.\"", "title": "" }, { "docid": "72168", "text": "The prime rate is the interest rate banks use amongst themselves to lend money to each other only. It is used as the basis (sometimes) for what interest rate banks charge you. The prime rate is based loosely on the Fed rate. There is a committee that meets regularly to set this and other industry interest rates. http://en.wikipedia.org/wiki/Prime_rate I am not 100% positive the following is totally accurate The banks keep our deposits and pay us interest for doing so. They are paying us interest because they take yours, mine and everybody elses deposits as a large lump sum and invest that money. Sometimes as business loans, sometimes as mortgages and sometimes as credit card. The banks have a book of business that will be EXACTLY how much credit they have extended to everybody. But they do not keep that amount of cash in the vaults, only some smaller percentage of that large amount. When I use my credit card and they need to transfer money to amazon.com, if they don't happen to have enough cash that day, they will just borrow from another bank that does, and the interest rate they pay to do so is the prime rate. Since they are paying interest on the money they borrow to pay the debt I charged because they told me my credit was worth so much (...???...) they charge me a little bit more than that. Hence your credit card or mortgage's APR being based on the prime rate. I THINK that is what they do If I am wrong leave a comment and I will update, or the mods can.", "title": "" }, { "docid": "234286", "text": "\"If you are investing in a mortgage strictly to avoid taxes, the answer is \"\"pay cash now.\"\" A mortgage buys you flexibility, but at the cost of long term security, and in most cases, an overall decrease in wealth too. At a very basic level, I have to ask anyone why they would pay a bank a dollar in order to avoid paying the government 28 - 36 cents depending on your tax rate. After all, one can only deduct interest- not principal. Interest is like rent, it accrues strictly to the lender, not equity. In theory the recipient should be irrelevant. If you have a need to stiff the government, go ahead. Just realize you making a banker three times as happy. Additionally the peace of mind that comes from having a house that no banker can take away from you is, at least for me, compelling. If I have a $300,000 house with no mortgage, no payments, etc. I feel quite safe. Even if my money is tied up in equity, if a serious situation came along (say a huge doctors bill) I always have the option of a reverse mortgage later on. So, to directly counter other claims, yes, I'd rather have $300k in equity then $50k in equity and $225k in liquid assets. (Did you notice that the total net worth is $25k less? And that's even before one considers the cash flow implication of a continuing mortgage. I have no mortgage, and I'm 41. I have a lot of net worth, but the thing that I really like is that I have a roof over my head that no on e can take away from me, and sufficient savings to weather most crises). That said, a mortgage is not about total cost. It is about cash flow. To the extent that a mortgage makes your cash flow situation better, it provides a benefit- just not one that is quantifiable in dollars and cents. Rather, it is a risk/reward situation. By taking a mortgage even when you have the cash, you pay a premium (the interest rate) in order to have your funds available when you need it. A very simple strategy to calculate and/or minimize this risk would be to invest the funds in another investment. If your rate of return exceeds the interest rate minus any tax preference (e.g. 4% minus say a 25% deduction = 3%), your money is better off there, obviously. And, indeed, when interest rates are only 4%, it may may be possible to find that. That said, in most instances, a CD or an inflation protected bond or so won't give you that rate of return. There, you'd need to look at stocks- slightly more risky. When interest rates are back to normal- say 5 or 6%, it gets even harder. If you could, however, find a better return than the effective interest rate, it makes the most sense to do that investment, hold it as a hedge to pay off the mortgage (see, you get your security back if you decide not to work!), and pocket the difference. If you can't do that, your only real reason to hold the cash should be the cash flow situation.\"", "title": "" }, { "docid": "403077", "text": "they may be willing to issue mortgages with smaller deposits, but may take longer to make a decision That cannot be farther from the truth. If you are getting a mortgage on a smaller deposit, you will be paying a higher interest rate. Time to take a decision depends very much on your credit situation, earnings, spending and the amount of loan you want to avail of. advantages and disadvantages compared to banks today Nothing specifically that is obvious. You deposits are guaranteed by FSCS, which is primarily everybody's biggest concern. One thing I did observe was they generally have saving accounts which pay better than the big banks, but that is for one to compare and find out. In ownership structure you own a part of the building society because you are a member by having an account(bank/mortgage) with them. Not the case with a big bank though unless you own any shares. You can make a case for the difference of the big bank's multiple business as compared to a building society.", "title": "" }, { "docid": "413169", "text": "My question is, how do you rebuild a home, without the money to rebuild the home? I ignorantly thought that was why we paid for insurance. The reason that you have insurance is so as to keep the mortgage lender from losing money. That's why you buy the insurance through the mortgage lender and they get paid. Without the insurance, you'd have no home but still have a mortgage. You'd either have to pay off a mortgage with no house or have to declare bankruptcy to shed the mortgage. You essentially have two paths. If you (or the builder/suppliers) can afford to float the cost, you can rebuild the original house. You'll eventually get the $161,000 and can pay off the builder and suppliers. This may involve taking out a construction mortgage to refinance the original mortgage. Presumably the construction mortgage would be with a different lender. The other path is that you can sell the existing property as is, and use the insurance and proceeds to pay off the existing mortgage. Then you'd have no house and no mortgage. You start over and buy a house with a mortgage. It's possible that your insurance payoff isn't enough to pursue either path. Then your option is to get the insurer to make a bigger payoff. This may involve suing them. Note that you may be able to talk the government into suing the insurer for you. They do have regulators who can review things. If you can't get government action, there are lawyers who will do the suing and take their fees out of their winnings.", "title": "" }, { "docid": "356388", "text": "\"Derivatives derive their value from underlying assets. This is expressed by the obligation of at least one counterparty to trade with the other counterparty in the future. These can take on as many combinations as one can dream up as it is a matter of contract. For futures, where two parties are obligated to trade at a specific price at a specific date in the future (one buyer, one seller), if you \"\"short\"\" a future, you have entered into a contract to sell the underlying at the time specified. If the price of the future moves against you (goes up), you will have to sell at a loss. The bigger the move, the greater the loss. You go ahead and pay this as well as a little extra to be sure that you satisfy what you owe due to the future. This satisfaction is called margin. If there weren't margin, people could take huge losses on their derivative bets, not pay, and disrupt the markets. Making sure that the money that will trade is already there makes the markets run smoothly. It's the same for shorting stocks where you borrow the stock, sell it, and wait. You have to leave the money with the broker as well as deposit a little extra to be sure you can make good if the market moves to a large degree against you.\"", "title": "" }, { "docid": "497075", "text": "I'm of the belief that you should always put 20% down. The lower interest rate will save you thousands over the life of the loan. Also PMI is no different then burning that much cash in the fireplace every month. From Wikipedia Lenders Mortgage Insurance (LMI), also known as Private mortgage insurance (PMI) in the US, is insurance payable to a lender or trustee for a pool of securities that may be required when taking out a mortgage loan. It is insurance to offset losses in the case where a mortgagor is not able to repay the loan and the lender is not able to recover its costs after foreclosure and sale of the mortgaged property. You are basically paying money each month for the bank to be insured against you not paying your mortgage. But in actuality the asset of the condo should be that insurance. Only you can decide if you are comfortable with having $50k in liquidity or not. It sounds like a good cushion to me but I don't know the rest of your expenses.", "title": "" } ]
PLAIN-1984	rash	[ { "docid": "MED-5128", "text": "BACKGROUND: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE: We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. DESIGN: Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995. RESULTS: Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant. CONCLUSIONS: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.", "title": "Low vitamin B-12 status and risk of cognitive decline in older adults." }, { "docid": "MED-2016", "text": "BACKGROUND: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet. METHODS: A market basket of products identified by name brand, weight or package size for both regular wheat-based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed. RESULTS: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P <or= 0.05). Bread and pasta was twice as expensive as their wheat-based counterparts. Cost was affected more by shopping venue than geographic location. CONCLUSIONS: This study demonstrated that gluten-free foods have poor availability and are more expensive than their gluten-containing counterparts. The impact of these findings on dietary compliance and the quality of life needs to be addressed.", "title": "Economic burden of a gluten-free diet." }, { "docid": "MED-5131", "text": "The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.", "title": "Vitamin B12 sources and bioavailability." }, { "docid": "MED-2037", "text": "Celiac disease is an immune-mediated inflammatory disorder of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals. Over the past several years, the concept of non-celiac gluten sensitivity (NCGS) has gained significant interest from the scientific community and mass media and the number of individuals embracing a gluten-free diet is rapidly growing. This condition is characterized by gastrointestinal or extraintestinal symptoms that respond to gluten withdrawal without evidence for underlying celiac disease or wheat allergy. Symptoms display significant overlap with the irritable bowel syndrome. Many important factors regarding this relatively novel condition remain to be elucidated; no discriminative markers to support a diagnosis of gluten sensitivity have been identified yet and its pathogenesis remains obscure. Here we review the current knowledge on NCGS, and outline potential pathogenic pathways of different gluten related disorders in order to gain clues about the pathophysiology of this novel condition.", "title": "Non-celiac gluten sensitivity. Is it in the gluten or the grain?" }, { "docid": "MED-1317", "text": "A high intake of whole grain foods is associated with reduced risk of colon cancer, but the mechanism underlying this protection has yet to be elucidated. Chronic inflammation and associated cyclooxygenase-2 (COX-2) expression in the colon epithelium are causally related to epithelial carcinogenesis, proliferation, and tumor growth. We examined the effect of avenanthramides (Avns), unique polyphenols from oats with anti-inflammatory properties, on COX-2 expression in macrophages, colon cancer cell lines, and on proliferation of human colon cancer cell lines. We found that Avns-enriched extract of oats (AvExO) had no effect on COX-2 expression, but it did inhibit COX enzyme activity and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide-stimulated mouse peritoneal macrophages. Avns (AvExO, Avn-C, and the methylated form of Avn-C (CH3-Avn-C)) significantly inhibited cell proliferation of both COX-2-positive HT29, Caco-2, and LS174T, and COX-2-negative HCT116 human colon cancer cell lines, CH3-Avn-C being the most potent. However, Avns had no effect on COX-2 expression and PGE(2) production in Caco-2 and HT29 colon cancer cells. These results indicate that the inhibitory effect of Avns on colon cancer cell proliferation may be independent of COX-2 expression and PGE(2) production. Thus, Avns might reduce colon cancer risk through inhibition of macrophage PGE(2) production and non-COX-related antiproliferative effects in colon cancer cells. Interestingly, Avns had no effect on cell viability of confluence-induced differentiated Caco-2 cells, which display the characteristics of normal colonic epithelial cells. Our results suggest that the consumption of oats and oat bran may reduce the risk of colon cancer not only because of their high fiber content but also due to Avns, which attenuate proliferation of colonic cancer cells.", "title": "Avenanthramides inhibit proliferation of human colon cancer cell lines in vitro." }, { "docid": "MED-2027", "text": "Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance. © 2014 American Society for Parenteral and Enteral Nutrition.", "title": "Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity." }, { "docid": "MED-1312", "text": "The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.", "title": "Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin." }, { "docid": "MED-5132", "text": "Vitamin B12 deficiency anemia may have psychiatric manifestations preceding the hematological symptoms. Although a variety of symptoms are described, there are only sparse data on the role of vitamin B12 in depression. We report a case of vitamin B12 deficiency presenting with recurrent episodes of depression.", "title": "Role of vitamin B12 in depressive disorder--a case report." }, { "docid": "MED-2013", "text": "As the gluten-free diet (GFD) gains in popularity with the general public, health practitioners are beginning to question its real health benefits. For those patients with celiac disease (CD), the GFD is considered medical nutrition therapy, as well as the only proven treatment that results in improvements in symptomatology and small bowel histology. Those with wheat allergy also benefit from the GFD, although these patients often do not need to restrict rye, barley, and oats from their diet. Gluten sensitivity is a controversial subject, where patients who have neither CD nor wheat allergy have varying degrees of symptomatic improvement on the GFD. Conditions in this category include dermatitis herpetiformis (DH), irritable bowel syndrome (IBS), and neurologic diseases such as gluten-sensitive ataxia and autism. It is important for patients and healthcare practitioners to understand the differences between these conditions, even though they may all respond to a GFD. Patients with CD can experience comorbid nutrition deficiencies and are at higher risk for the development of cancers and other autoimmune conditions. Those with wheat allergy and gluten sensitivity are thought not to be at higher risk for these complications. Defining the symptoms and biochemical markers for gluten-sensitive conditions is an important area for future investigations, and high-quality, large-scale randomized trials are needed to prove the true benefits of the GFD in this evolving field.", "title": "Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad." }, { "docid": "MED-1313", "text": "Current treatment modalities for epidermal growth factor (EGFR)-positive cancers have recently included the use of antibodies and small-molecule tyrosine-kinase inhibitors (TKI). A significant limiting step in the use of these agents is dermatological toxicity, frequently in the form of an acneiform eruption. Present management modalities for this toxicity are largely ineffective. Colloidal oatmeal lotion demonstrates multiple anti-inflammatory properties with known effects on arachidonic acid, cytosolic phospholipase A2 and tumour necrosis factor-alpha pathways, along with an excellent side-effect profile. Treatment with colloidal oatmeal was applied to 11 patients with a rash induced by cetuximab, erlotinib, panitumumab and sorafenib. Of the 10 assessable patients, 6 had complete response and 4 partial response, giving a response rate of 100% with no associated toxicities. Treatment with colloidal oatmeal lotion is efficient in controlling the rash associated with EGFR and multiple TKI, and allows continuation of the antineoplastic treatment.", "title": "Effect of treatment with a colloidal oatmeal lotion on the acneform eruption induced by epidermal growth factor receptor and multiple tyrosine-kina..." }, { "docid": "MED-1316", "text": "Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses. In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available. Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams. Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003. Its preparation is also standardized by the United States Pharmacopeia. The many clinical properties of colloidal oatmeal derive from its chemical polymorphism. The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat. The presence of different types of phenols confers antioxidant and anti-inflammatory activity. Some of the oat phenols are also strong ultraviolet absorbers. The cleansing activity of oat is mostly due to saponins. Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.", "title": "Colloidal oatmeal: history, chemistry and clinical properties." }, { "docid": "MED-5129", "text": "BACKGROUND: Vitamin B(12) deficiency can occur in individuals with dietary patterns that exclude animal foods and patients who are unable to absorb vitamin B(12 )in food. MATERIAL AND METHOD: Our clinic serves a high-income population living in Southern Israel. We hypothesize that a tendency to decrease of level of vitamin B(12) in our population is caused by a premeditated decrease in consumption of animal products. We analyzed 512 medical histories of patients undergoing blood tests for vitamin B(12) level for various reasons. RESULT: The level of vitamin B(12) in 192 patients (37.5%) was less than 250 pg/ml. CONCLUSION: As a result of media information disseminating the relationship between meat, cholesterol and cardiovascular diseases, consumption of meat, particularly beef, has decreased. Changes in life style among segments of the population with high socioeconomic level, on one hand, and the existence of poverty, on the other, are two main factors in the decreasing consumption of animal products. This causes a decrease in the level of vitamin B(12) in the general population, and as a consequence, this will increase pathology due to vitamin B(12) deficiency. In lieu of these possible developments and in order to prevent serious health problems, vitamin B(12) fortification should be seriously considered and discussed. (c) 2007 S. Karger AG, Basel.", "title": "Modern society and prospects of low vitamin B12 intake." }, { "docid": "MED-5130", "text": "Although cobalamin deficiency is widely known and usually presents with hematologic and neuropsychiatric manifestations, the psychiatric symptoms are not usually the predominant manifestation. We describe a young single male vegetarian who developed a cobalamin-induced psychotic episode without preceding neurologic manifestations and without any hematologic symptoms. He recovered after a short course of antipsychotics and oral cobalamin supplementation and remained asymptomatic and functionally independent at 1 year of follow-up.", "title": "Schizophrenia-like psychotic episode precipitated by cobalamin deficiency." }, { "docid": "MED-1314", "text": "The use of epidermal growth factor receptor (EGFR) inhibitors for the treatment of solid tumours is increasing. However, the tolerability profile for EGFR-inhibitors, such as the monoclonal antibody cetuximab and the tyrosine kinase inhibitor erlotinib, is characterised by a unique group of skin reactions dominated by an acneiform eruption, xerosis, eczema and changes in the hair and nails. The possibility that this skin toxicity correlates with anti-tumour activity offers the potential to titrate dosing on a case-by-case basis. These skin effects may constitute a significant obstacle to treatment compliance. Accordingly, there is a need for consistent, multi-disciplinary management strategies that will allow patients to receive the recommended dosages of such targeted therapies. The eruption responds well to some acne therapies and xerosis can be controlled by standard emollients. Here we present an overview of the treatment options for skin reactions that are available today, and evaluate some of the ways in which the treatment of such EGFR-inhibitor-related skin reactions may be improved in the future. Evidence-based studies are needed to determine the best way to manage these effects.", "title": "The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies." }, { "docid": "MED-2033", "text": "BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this \"new\" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms \"wheat (hyper)sensitivity,\" \"wheat allergy,\" \"wheat intolerance,\" \"gluten (hyper)sensitivity,\" and \"gluten intolerance,\" and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.", "title": "Non-celiac gluten sensitivity: literature review." }, { "docid": "MED-5135", "text": "Vitamin B(12) deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B(12) deficiency can be difficult when the typical macrocytic anaemia is absent. We report the case of a 10-month-old female diagnosed with West syndrome associated with vitamin B(12) deficiency but without macrocytic anaemia caused by nutritional inadequacy in the mother. The patient's motor skills and cognitive development were normal until she was 9 months old, when she began to exhibit a series of sudden flexions of the head, trunk, arms, and legs. She was exclusively breast-fed and had received no vitamin supplementation. Results of electroencephalography (EEG) indicated modified hypsarrhythmia and the patient was diagnosed as having West syndrome. Synthetic adrenocorticotropic hormone was administered and although her spasms had resolved, the patient remained apathic and could not sit without assistance. EEG results indicated generalized slow activity. After she was diagnosed as having vitamin B(12) deficiency, parenteral treatment with vitamin B(12) was initiated. Her symptoms resolved and EEG was completely normal. When she was 20 months old she exhibited an age-appropriate developmental and neurological profile. To our knowledge, this is the first report of West syndrome as a presenting symptom of vitamin B(12) deficiency.", "title": "West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia." }, { "docid": "MED-1311", "text": "Although Erbitux (cetuximab) has proven therapeutic benefit in the clinical setting, the molecular determinants predicting responsiveness to this agent are still not very well understood. Here, we assessed the relationship between basal total and activated (pY1068) epidermal growth factor receptor (EGFR) levels in a tumor and the responsiveness to cetuximab monotherapy or combination-based treatment using human xenograft models. Cetuximab treatment alone (0.25-1 mg/mouse/injection, q3d, i.p.) effectively delayed the growth of GEO and L2987 tumors by a minimum of 10 days corresponding to log cell kill values of >or=1.0. Borderline activity was seen in the A549 and WiDr xenografts. However, cetuximab failed to show any significant antitumor activity in the HT29, HCT116, LOVO, Colo205, LX-1, HCC70, and N87 models. All of the studied tumors had detectable yet variable levels of EGFR. For combination regimens, cetuximab (1 mg/mouse/injection, q3dx5, i.p.) and cisplatin (4.5 mg/kg/injection, q3dx5, i.v.) proved to be significantly more efficacious than individual monotherapies in the cisplatin-refractory yet cetuximab-responsive GEO tumor model (P < 0.001). However, no therapeutic enhancement was observed in the cisplatin and cetuximab weakly responsive A549 xenograft. Similarly, combinations of CPT-11 (48 mg/kg/injection, q3dx5, i.v.) with cetuximab (1 mg/mouse/injection, q3dx5, i.p.) failed to show any improvements over individual monotherapies in the cetuximab resistant/weakly responsive HT29, A549, and WiDr models. We conclude that preclinical activity associated with cetuximab monotherapy does not correlate directly with relative basal levels of total or activated (pY1068) EGFR in a tumor. Moreover, robust single-agent activity by cetuximab may be the best predictor for this agent to potentiate chemotherapy-mediated antitumor activities.", "title": "Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth facto..." }, { "docid": "MED-1315", "text": "PURPOSE: The EGFR-independent activation of the RAS/RAF/MEK/MAPK pathway is one of the resistance mechanisms to cetuximab. EXPERIMENTAL DESIGN: We have evaluated, in vitro and in vivo, the effects of BAY 86-9766, a selective MEK1/2 inhibitor, in a panel of human colorectal cancer cell lines with primary or acquired resistance to cetuximab. RESULTS: Among the colorectal cancer cell lines, five with a KRAS mutation (LOVO, HCT116, HCT15, SW620, and SW480) and one with a BRAF mutation (HT29) were resistant to the antiproliferative effects of cetuximab, whereas two cells (GEO and SW48) were highly sensitive. Treatment with BAY 86-9766 determined dose-dependent growth inhibition in all cancer cells, including two human colorectal cancer cells with acquired resistance to cetuximab (GEO-CR and SW48-CR), with the exception of HCT15 cells. Combined treatment with cetuximab and BAY 86-9766 induced a synergistic antiproliferative and apoptotic effects with blockade in the MAPK and AKT pathway in cells with either primary or acquired resistance to cetuximab. The synergistic antiproliferative effects were confirmed using other two selective MEK1/2 inhibitors, selumetinib and pimasertib, in combination with cetuximab. Moreover, inhibition of MEK expression by siRNA restored cetuximab sensitivity in resistant cells. In nude mice bearing established human HCT15, HCT116, SW48-CR, and GEO-CR xenografts, the combined treatment with cetuximab and BAY 86-9766 caused significant tumor growth inhibition and increased mice survival. CONCLUSION: These results suggest that activation of MEK is involved in both primary and acquired resistance to cetuximab and the inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance in patients with colorectal cancer. ©2014 American Association for Cancer Research.", "title": "Primary and acquired resistance of colorectal cancer cells to anti-EGFR antibodies converge on MEK/ERK pathway activation and can be overcome by co..." }, { "docid": "MED-2014", "text": "BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.", "title": "Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease." }, { "docid": "MED-5134", "text": "This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.", "title": "Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition." }, { "docid": "MED-5133", "text": "We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.", "title": "[Floppy baby with macrocytic anemia and vegan mother]." } ]	[ { "docid": "MED-2361", "text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.", "title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York." }, { "docid": "MED-2759", "text": "A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.", "title": "Vomiting from multivitamins: a potential drug interaction." }, { "docid": "MED-2360", "text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.", "title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness." }, { "docid": "MED-2052", "text": "The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV) treatment regimens has made treatment more effective and patient management more complex. Shepherding patients through a full course of HCV therapy requires motivation and involvement on the part of the patient and the physician. Indeed, physician inexperience and lack of confidence in guiding patients through the challenges of treatment appears to be a primary reason for early discontinuation of therapy. Among the many complications of HCV treatment that must be managed efficiently and effectively are depression and other psychiatric disorders; hematologic abnormalities including DAA- and ribavirin-associated anemia and peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug eruptions, including telaprevir-associated rash; and weight loss. Practical considerations in management of these common complications are offered. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA live continuing medical education course held in New York in June 2012.", "title": "Managing adverse effects and complications in completing treatment for hepatitis C virus infection." }, { "docid": "MED-2815", "text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin, a component of turmeric: from farm to pharmacy." }, { "docid": "MED-824", "text": "OBJECTIVE: To compare the clinical results and reproductive outcome in obese women with polycystic ovary syndrome (PCOS) following dietary intervention or treatment with metformin. METHODS: Forty-six patients with PCOS were studied prospectively in Prince Rashed Hospital, Irbid, Jordan, between January 2003 and April 2005. The women were randomly divided into 2 groups: Group 1 (n=24) was prescribed with 1200-1400 kcal/day diet (25% proteins, 25% fat, and 50% carbohydrates plus 25-30 gm of fiber per week). Group 2 (n=22) was assigned to take 850 mg of metformin twice in a continuous manner. Both treatments continued for 6 months. Clinical and biochemical data, before and after both treatments along with the reproductive outcome were compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups in terms of age, body mass index (BMI) and duration of infertility. Both groups had a significant improvement after treatment in the menstrual cyclicity (66.7% and 68.2% versus 12.5% and 18.2%) and significant reduction in BMI (mean of 27.4 and 27.8 versus 32.2 and 31.9), luteinizing hormone levels (7.9+/-1.7 and 6.9+/-1.8 versus 11.8+/-2.2 and 11.5+/-1.8), and androgen (testosterone, androstenedione, dehydroepiandrosterone sulfate) concentration. The clinical, biochemical, and reproductive outcome including menstrual cycle pattern, ovulation, and pregnancy rates were similar in both groups after treatment. CONCLUSION: Amelioration of hyperinsulinemia and hyperandrogenemia with dietary intervention or metformin treatment improves significantly the clinical features and reproductive function in overweight PCOS women.", "title": "Dietary intervention versus metformin to improve the reproductive outcome in women with polycystic ovary syndrome. A prospective comparative study." }, { "docid": "MED-1820", "text": "Background This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. Methodology/Principal Findings PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. Conclusions/Significance Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.", "title": "Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis" }, { "docid": "MED-2030", "text": "Background Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86.", "title": "An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity" }, { "docid": "MED-4197", "text": "Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.", "title": "Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation." }, { "docid": "MED-4133", "text": "BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.", "title": "Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study." }, { "docid": "MED-1247", "text": "Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective.", "title": "Antiemetic activity of volatile oil from Mentha spicata and Mentha × piperita in chemotherapy-induced nausea and vomiting" }, { "docid": "MED-1098", "text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.", "title": "Intake of dioxins and related compounds from food in the U.S. population." }, { "docid": "MED-2432", "text": "It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.", "title": "The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century." }, { "docid": "MED-2448", "text": "A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.", "title": "Clinical efficacy of apple polyphenol for treating cedar pollinosis." }, { "docid": "MED-2608", "text": "The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma longa) on the mutagenicity of several environmental mutagens were investigated in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our observations indicate that curcumin may alter the metabolic activation and detoxification of mutagens.", "title": "In vitro antimutagenicity of curcumin against environmental mutagens." }, { "docid": "MED-886", "text": "BACKGROUND: Both hempseed oil (HO) and flaxseed oil (FO) contain high amounts of essential fatty acids (FAs); i.e. linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), but almost in opposite ratios. An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes. It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile. AIM OF THE STUDY: To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids, plasma glucose and insulin, and haemostatic factors in healthy humans. METHODS: Fourteen healthy volunteers participated in the study. A randomised, double-blind crossover design was used. The volunteers consumed HO and FO (30 ml/day) for 4 weeks each. The periods were separated by a 4-week washout period. RESULTS: The HO period resulted in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters (CE) and triglycerides (TG) as compared with the FO period (P < 0.001), whereas the FO period resulted in a higher proportion of ALA in both serum CE and TG as compared with the HO period (P < 0.001). The proportion of arachidonic acid in CE was lower after the FO period than after the HO period (P < 0.05). The HO period resulted in a lower total-to-HDL cholesterol ratio compared with the FO period (P = 0.065). No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids, plasma glucose, insulin or hemostatic factors. CONCLUSIONS: The effects of HO and FO on the profile of serum lipids differed significantly, with only minor effects on concentrations of fasting serum total or lipoprotein lipids, and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors.", "title": "Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors." }, { "docid": "MED-4799", "text": "To determine the presence of Clostridium difficile, we sampled cooked and uncooked meat products sold in Tucson, Arizona. Forty-two percent contained toxigenic C. difficile strains (either ribotype 078/toxinotype V [73%] or 027/toxinotype III [NAP1 or NAP1-related; 27%]). These findings indicate that food products may play a role in interspecies C. difficile transmission.", "title": "Clostridium difficile in Retail Meat Products, USA, 2007" }, { "docid": "MED-2315", "text": "Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.", "title": "Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)" }, { "docid": "MED-4701", "text": "BACKGROUND: Vinegar reduces postprandial glycemia (PPG) in healthy adults. This study investigated the vinegar dosage (10 vs. 20 g), timing (during mealtime vs. 5 h before meal) and application (acetic acid as vinegar vs. neutralized salt) for reducing PPG. METHODS: Four randomized crossover trials were conducted in adults (n = 9-10/trial) with type 2 diabetes (1 trial) or without diabetes (3 trials). All trials followed the same protocol: a standardized meal the evening prior to testing, an overnight fast ( 1 10 h) and 2-hour glucose testing following consumption of a bagel and juice test meal (3 trials) or dextrose solution (1 trial). For each trial, PPG was compared between treatments using area-under-the-curve calculations 120 min after the meal. RESULTS: Two teaspoons of vinegar ( 10 g) effectively reduced PPG, and this effect was most pronounced when vinegar was ingested during mealtime as compared to 5 h before the meal. Vinegar did not alter PPG when ingested with monosaccharides, suggesting that the antiglycemic action of vinegar is related to the digestion of carbohydrates. Finally, sodium acetate did not alter PPG, indicating that acetate salts lack antiglycemic properties. CONCLUSIONS: The antiglycemic properties of vinegar are evident when small amounts of vinegar are ingested with meals composed of complex carbohydrates. In these situations, vinegar attenuated PPG by 20% compared to placebo. 2009 S. Karger AG, Basel.", "title": "Examination of the antiglycemic properties of vinegar in healthy adults." }, { "docid": "MED-3355", "text": "OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.", "title": "Recent fat intake modulates fat taste sensitivity in lean and overweight subjects." }, { "docid": "MED-4667", "text": "Cows with isolation of Staphylococcus aureus approximately 1 week after calving and milk yield, somatic cell count (SCC), clinical mastitis (CM), and culling risk through the remaining lactation were assessed in 178 Norwegian dairy herds. Mixed models with repeated measures were used to compare milk yield and SCC, and survival analyses were used to estimate the hazard ratio for CM and culling. On average, cows with an isolate of Staph. aureus had a significantly higher SCC than culture-negative cows. If no post-milking teat disinfection (PMTD) was used, the mean values of SCC were 42,000, 61,000, 68,000 and 77,000 cells/ml for cows with no Staph. aureus isolate, with Staph. aureus isolated in 1 quarter, in 2 quarters and more than 2 quarters respectively. If iodine PMTD was used, SCC means were 36,000; 63,000; 70,000 and 122,000, respectively. Primiparous cows testing positive for Staph. aureus had the same milk yield curve as culture-negative cows, except for those with Staph. aureus isolated in more than 2 quarters. They produced 229 kg less during a 305-d lactation. Multiparous cows with isolation of Staph. aureus in at least 1 quarter produced 94-161 kg less milk in 2nd and >3rd parity, respectively, and those with isolation in more than 2 quarters produced 303-390 kg less than multiparous culture-negative animals during a 305-d lactation. Compared with culture-negative cows, the hazard ratio for CM and culling in cows with isolation of Staph. aureus in at least 1 quarter was 2.0 (1.6-2.4) and 1.7 (1.5-1.9), respectively. There was a decrease in the SCC and in the CM risk in culture-negative cows where iodine PMTD had been used, indicating that iodine PMTD has a preventive effect on already healthy cows. For cows testing positive for Staph. aureus in more than 2 quarters at calving, iodine PMTD had a negative effect on the CM risk and on the SCC through the remaining lactation.", "title": "Association between isolation of Staphylococcus aureus one week after calving and milk yield, somatic cell count, clinical mastitis, and culling th..." }, { "docid": "MED-5004", "text": "BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.", "title": "Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford." }, { "docid": "MED-5192", "text": "High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.", "title": "A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland)." }, { "docid": "MED-3163", "text": "Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARγ), and PPARγ coactivators PGC1α and PGC1β only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.", "title": "Antioxidants prevent health-promoting effects of physical exercise in humans" }, { "docid": "MED-2252", "text": "Studies suggested the intake of Cd from diet can be approximately equivalent to that from smoking. Moreover, a mutual metabolic influence between Cd and nutrients has been reported. The purpose of this study was to evaluate the relationship between blood cadmium concentration (BCdC) and food consumption, nutrients intake (Ca, Fe, Zn, vitamin C, and vitamin D), tobacco smoking, and some other variables (age, body mass index, and residence) in 243 adults living in the Italian island of Sardinia (Sassari Province). Specifically, we hypothesized that offal consumption contributes to Cd intakes and blood levels. The BCdC was quantified by graphite furnace atomic absorption spectrometry, and information on personal data was collected through questionnaires. Smoke significantly contributed to the BCdC (P < .001). Nonsmoker subjects who eat offal showed significantly higher BCdC (P = .04). Moreover, slightly higher BCdCs were also observed in nonsmoker subjects who eat rice, fish, and bread. The BCdC positively correlated with age of subjects (r = 0.144; P = .025) and offal daily intake in nonsmokers (r = 0.393; P < .001). The intake of Ca was negatively correlated (r = -0.281; P = .001) with the BCdC in females. The multiple linear regression analysis showed smoking > consumption of offal > body mass index ≈ age as the most important risk factors for the BCdC in the selected population. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Diet and nutrients are contributing factors that influence blood cadmium levels." }, { "docid": "MED-3506", "text": "BACKGROUND: A reduced rectal perceptual threshold has been reported in patients with irritable bowel syndrome (IBS), but this phenomenon may be induced by a comorbid psychological state. We evaluated the rectal pain threshold at baseline and after conditioning (repetitive rectal painful distention: RRD) in patients with IBS or functional abdominal pain syndrome (FAPS), which is an abdominal pain disorder, and in healthy controls, and determined whether rectal hypersensitivity is a reliable marker for IBS. METHODS: The rectal sensory threshold was assessed by a barostat. First, a ramp distention of 40 ml/min was induced, and the threshold of pain and the maximum tolerable pressure (mmHg) were measured. Next, RRD (phasic distentions of 60-s duration separated by 30-s intervals) was given with a tracking method until the subjects had complained of pain six times. Finally, ramp distention was induced again, and the same parameters were measured. The normal value was defined by calculating the 95% confidence intervals of controls. RESULTS: Five or six of the seven IBS patients showed a reduced rectal pain threshold or maximum tolerable pressure, respectively, at baseline. In all patients with IBS, both thresholds were reduced after RRD load, but they were reduced in none of the patients with FAPS. RRD significantly reduced both thresholds in the IBS group (P < 0.05), but it had no effect in the control or FAPS groups. CONCLUSIONS: Rectal hypersensitivity induced by RRD may be a reliable marker for IBS. Conditioning-induced visceral hypersensitivity may play a pathophysiologic role in IBS.", "title": "Repetitive rectal painful distention induces rectal hypersensitivity in patients with irritable bowel syndrome." }, { "docid": "MED-3295", "text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.", "title": "Cancer and Noncancer Mortality Among American Seafood Workers" }, { "docid": "MED-4824", "text": "In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.", "title": "4. Chronic pancreatitis and pancreatic cancer, lifestyle-related diseases." }, { "docid": "MED-4181", "text": "Exposure of pregnant women to organochlorine (OC) pesticides largely derives from contaminated food, but environmental, occupational, and domestic factors have also been implicated. We investigated the presence of nine OC residues in the umbilical cord blood of newborns in Southern Spain and analyzed the relationship of this exposure with maternal and pregnancy variables, including maternal adherence to the Mediterranean Diet (MD). OCs were detected in 95% of umbilical cord blood samples from the 318 mothers, who had a mean degree of adherence to the MD of 56.77 (SD: 16.35) (range, 0-100). The MD prioritizes consumption of vegetable and fruit over meat and dairy products, and OCs are generally lipophilic molecules that accumulate in foods of animal origin. Consumption of meat, fish, and dairy products was associated with dichlorodiphenyldichloroethylene (DDE) in umbilical cord serum, and dairy product intake with lindane. Vegetable consumption was also associated with lindane and fruit intake with endosulfan I. We found no significant association between MD adherence and the presence of OC residues in serum. However, closer adherence to the MD may offer greater protection against OC exposure because of its reduced content in meat and dairy products. Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "title": "Organochlorine pesticides in umbilical cord blood serum of women from Southern Spain and adherence to the Mediterranean diet." }, { "docid": "MED-1551", "text": "In a controlled trial, 21 strict vegetarians were studied prospectively for eight weeks: a two-week control period of the usual vegetarian diet was followed by four weeks, during which 250 g of beef was added isocalorically to the daily vegetarian diet and then by two weeks of the control diet. Plasma high-density lipoprotein-cholesterol did not change during the study, whereas plasma total cholesterol rose significantly by 19% at the end of the meat-eating period. Systolic blood pressure (BP) increased significantly during the meat eating by 3% over control values, whereas diastolic BP showed no major changes. Plasma renin activity, prostaglandin A and E levels, and urinary kallikrein, norepinephrine, and epinephrine excretions were within normal limits and did not change notably throughout the trial. The study suggests an adverse effect of consumption of beef on plasma lipid and BP levels.", "title": "Effect of ingestion of meat on plasma cholesterol of vegetarians." } ]
4182	What expenses do most people not prepare for that turn into “emergencies” but are not covered by an Emergency Fund?	[ { "docid": "119244", "text": "\"Annual property tax and home insurance come to mind as things that are easily forgotten, but surely the biggest true, \"\"I didn't see that coming,\"\" is a major car repair. There are a number of things that can go wrong with a car with little warning and end up costing a thousand dollars or more. Since most people are dependent upon their car for getting to work, doing anything but fixing or replacing the car is not an option. If you fix it, that's an out of pocket expense that most aren't prepared for. If the car has some age, you might be inclined to replace it, but doing so in a rush costs a lot more than taking your time in such a decision.\"", "title": "" }, { "docid": "420265", "text": "Here's a few. Is this what you're looking for? Also this should probably be a community wiki.", "title": "" }, { "docid": "329217", "text": "Extended illness/disability that prevents you from being able to work. Edit: Leigh Riffel: So, why should this be expected, and how should it be planned for? Some of us may be fortunate enough that this never happens, but I've known enough unlucky people to have seen that it can and does happen. Prepare for it with:", "title": "" }, { "docid": "573067", "text": "While it is true that homeowners insurance will cover emergencies, it is very important to check and make sure that your policy is covering everything that it needs to. A great example is what happened to all of those without flood insurance in Tennessee last year. You may opt not to get additional coverage, but then you should make sure that you are setting aside funds for such a catastrophe.", "title": "" }, { "docid": "143236", "text": "\"Some things are nearly universal, and have been mentioned already. My \"\"favorite\"\" forseeable expenses in this category are: However, I also advocate saving for expenses that are specific to you. Look back on your expenses for the last 12 months, minimum (18 or 24 may be better). Ask yourself these questions: I ask about large expenditures because you may make enough that you can \"\"eat\"\" these lapses in budgeting, as I did for many years. It is not an emergency now, but it turned into an emergency down the road as my spending went out of control. Look at all expenditures over a certain level, say $100 or $200. Some personal examples of expenses that aren't quite so universal, but turned into small emergencies: This last one was rather unexpected. It is the reason why I ask the question \"\"why didn't I budget for it?\"\" These fees and dues are for my professional-level certifications. In my industry, they are \"\"always\"\" paid for by the company. A year ago, they weren't paid by my former employer because they planned to lay me off. This year, they weren't paid by my present employer because I am technically a temporary worker (4 years is temporary?). So, from now on, I plan to save for this expense. If my employer pays my dues, then I stop saving for the expense, but keep the money I've saved.\"", "title": "" }, { "docid": "108814", "text": "The most obvious one these days is unexpected and extended unemployment. If you are living paycheck to paycheck, you are asking for trouble in this economy.", "title": "" }, { "docid": "371624", "text": "The way you ask this is interesting, it implies (quite correctly) that for many, an annual bill for house insurance, property tax, etc, can turn into an emergency. My answer to the true emergency is a breakage that can't be foreseen (although you have to know the furnace isn't going to last forever) or a medical bill that's not covered (our dental is limited and the Mrs root canal can be $1000 out of pocket)", "title": "" }, { "docid": "110732", "text": "insurance premiums My annual car premium always caught me off guard until I set up a dedicated savings account for it.", "title": "" } ]	[ { "docid": "179702", "text": "\"An emergency fund is very well defined, both on this site and across the web. An emergency fund is a cash account where you keep money for emergencies so you don't need to take on debt like a loan or credit cards. Car breaks down? emergency fund can help pay that. Lose your job? The emergency fund is there to pay rent and for groceries until you're back up an running. There are several schools of thought on how much money should be in your emergency fund, but it boils down to how high your risk assessment is. Typically, the average is to have 3 months in cash available at all times (like in a savings account). It'd be better to have more, but that's a typical goal. You're also asking about investments in the comments. An emergency fund should be readily available. If you already have $10K in savings, set aside what you would need to cover a few months of bills into a cash-ready savings account, then invest the rest. Investments sometimes take time, or have penalties, if you withdraw them. Additionally, as @JoeTaxpayer so correctly pointed out, getting into the habit of maintaining a separate emergency fund helps protect your other investments from becoming a crutch and instead used to save up for larger things like a house or, especially, retirement. See also: What expenses should be covered by an emergency fund What should I reserve \"\"emergency savings\"\" for? What expenses do most people not prepare for that turn into \"\"emergencies\"\" but are not covered by an Emergency Fund? Less than a year at my first job out of college, what do I save for first?\"", "title": "" }, { "docid": "406286", "text": "The rule that I know is six months of income, stored in readily accessible savings (e.g. a savings or money market account). Others have argued that it should be six months of expenses, which is of course easier to achieve. I would recommend against that, partially because it is easier to achieve. The other issue is that people are more prone to underestimate their expenses than their income. Finally, if you base it on your current expenses, then budget for savings and have money left over, you often increase your expenses. Sometimes obviously (e.g. a new car) and sometimes not (e.g. more restaurants or clubs). Income increases are rarer and easier to see. Either way, you can make that six months shorter or longer. Six months is both feasible and capable of handling difficult emergencies. Six years wouldn't be feasible. One month wouldn't get you through a major emergency. Examples of emergencies: Your savings can be in any of multiple forms. For example, someone was talking about buying real estate and renting it. That's a form of savings, but it can be difficult to do withdrawals. Stocks and bonds are better, but what if your emergency happens when the market is down? Part of how emergency funds operate is that they are readily accessible. Another issue is that a main goal of savings is to cover retirement. So people put them in tax privileged retirement accounts. The downside of that is that the money is not then available for emergencies without paying penalties. You get benefits from retirement accounts but that's in exchange for limitations. It's much easier to spend money than to save it. There are many options and the world makes it easy to do. Emergency funds make people really think about that portion of savings. And thinking about saving before spending helps avoid situations where you shortchange savings. Let's pretend that retirement accounts don't exist (perhaps they don't in your country). Your savings is some mix of stocks and bonds. You have a mortgaged house. You've budgeted enough into stocks and bonds to cover retirement. Now you have a major emergency. As I understand your proposal, you would then take that money out of the stocks and bonds for retirement. But then you no longer have enough for retirement. Going forward, you will have to scrimp to get back on track. An emergency fund says that you should do that scrimping early. Because if you're used to spending any level of money, cutting that is painful. But if you've only ever spent a certain level, not increasing it is much easier. The longer you delay optional expenses, the less important they seem. Scrimping beforehand also helps avoid the situation where the emergency happens at the end of your career. It's one thing to scrimp for fifteen years at fifty. What's your plan if you would have an emergency at sixty-five? Or later? Then you're reducing your living standard at retirement. Now, maybe you save more than necessary. It's not unknown. But it's not typical either. It is far more common to encounter someone who isn't saving enough than too much.", "title": "" }, { "docid": "343457", "text": "\"What could a small guy with $100 do to make himself not poor? The first priority is an emergency fund. One of the largest expenses of poor people are short-term loans for emergencies. Being able to avoid those will likely be more lucrative than an S&P investment. Remember, just like a loan, if you use your emergency fund, you'll need to refill it. Be smart, and pay yourself 10% interest when you do. It's still less than you'd pay for a payday loan, and yet it means that after every emergency you're better prepared for the next event. To get an idea for how much you'd need: you probably own a car. How much would you spend, if you suddenly had to replace it? That should be money you have available. If you think \"\"must\"\" buy a new car, better have that much available. If you can live with a clunker, you're still going to need a few K. Having said that, the next goal after the emergency fund should be savings for the infrequent large purchases. The emergency fund if for the case where your car unexpectedly gets totaled; the saving is for the regular replacement. Again, the point here is to avoid an expensive loan. Paying down a mortgage is not that important. Mortgage loans are cheaper than car loans, and much cheaper than payday loans. Still, it would be nice if your house is paid when you retire. But here chances are that stocks are a better investment than real estate, even if it's the real estate you live in.\"", "title": "" }, { "docid": "14989", "text": "I know this is heresy but if you have funds for significantly more than 6 months of expenses (let's say 12 months), how risky would it be to put it all into stock index funds? Quite risky as if you do need to dip into it, how fast could you get the cash? Also, do you realize the tax implications when you do sell the shares should you have an emergency? In the worst-case scenario, let's say you have a financial emergency at the same time the stock market crashes and loses half its value. You could still liquidate the rest and have sufficient funds for 6 months. Am I underestimating the risks of this strategy? That's not worst case scenario though. Worst case scenario would be another 9/11 where the markets are closed for nearly a week and you need the money but can't get the funds converted to cash in the bank that you can use. This is in addition to the potential wait for a settlement in the case of using ETFs if you choose to go that way. In the case of money market funds, CDs and other near cash equivalents these can be accessed relatively easily which is part of the point. A staggered approach where some cash is kept in house, some in accounts that can easily accessed and some in other investments may make sense though the breakdown would differ depending on how much risk people are willing to take. If it truly is an emergency fund then the odds of needing it should be very slim, so why live with near zero return on that money? Something to consider is what is called an emergency here? For some people a sudden $1,000 bill to fix their car that just broke down is an emergency. For others, there could be emergency trips to visit family that may have gotten into accidents or gotten a diagnosis that they may pass away soon. Consider what do you want to call an emergency here as chances are you may not be considering all that people would think is an emergency. There is the question of what other sources of money do you have to cover should issues arise.", "title": "" }, { "docid": "362887", "text": "\"Which of these categories are emergency funds meant to cover? Emergency funds are for emergencies, which to me means expenses that are unanticipated and can't be covered out of \"\"normal\"\" cash-flow. Oil changes are not an \"\"emergency\"\" and should be part of your normal budget. Car/house repairs and doctor visits might be an emergency depending on the severity and the urgency (e.g. do I need to fix this now or can I save up and fix it?) For known, predictable expenses that are infrequent (Christmas, birthdays, car insurance, home insurance/taxes if it's not part of your mortgage payment), I use an escrow account. I calculate how much I'll need for all of those things put together over the year and set aside a fixed amount each paycheck to ensure that I have enough to cover each item. You could do something similar for minor doctor visits, car repairs, etc. Estimate how much you might spend and set aside some money each month. If you find you're spending more than you thought, just increase the amount. You can use envelopes for each type of expense, have a separate checking account for those, whatever. The point is to set it aside and make sure you have enough left over to cover your known expenses. The whole point of an emergency fund is to be able to pay cash for emergencies rather than borrowing to pay them and dealing with interest, late fees, etc.\"", "title": "" }, { "docid": "206431", "text": "I know an answer has been accepted, but you need an emergency fund, ideally enough to cover at least 3 months of after-tax basic living expenses. As a free-lancer, 6 months would be even better. This isn't a fun way to tie up your money, but it is a prudent way. What if you lose your job, or decide you want to change your line of work? What if you're told a close family member has only months to live and you want to take significant time off unpaid? What if your car breaks down and you need a new one? What if your freelance business hits a dry patch for a few months? What if you want to move but can't sell your next house quickly? I've known people who had these types of situations come up unexpectedly. Some were financially prepared and had the freedom to make the choices they wanted to make, others didn't and now have regrets. Once you have a basic emergency fund in place, then go for investing with the rest of the money. Best of luck!", "title": "" }, { "docid": "242011", "text": "An emergency fund is about managing risk. What would you do if your furnace, water heater, and cars all broke down at the same time? Being in Michigan, I can imagine that you wouldn't want to take cold showers, heat the entire house by wood fire, and walk to work every day. So how do you manage this risk? What would happen if you lost your job and couldn't find one for a few months? By only having $5k in the bank in an emergency fund, you are putting your family at risk. If these sorts of things happened, you would be in trouble. You would have to borrow money either hurting equity in the home that you have worked hard to build up, or by some other means. You and your spouse should sit down and decide what a good emergency fund looks like for your family. A reserve of 3-6 months of expenses is a good emergency fund. This could cover your family in the event of a lost job while you look for a new one. It would also cover you when Murphy strikes and things break down all at the same time. Once you and your spouse have determined how much you want to set aside, you two must determine how you will get there. Maybe you put in some extra hours at work, maybe you lower the retirement contributions temporarily, maybe you try to pay off the car as quickly as possible then put what you were paying on the car into the emergency fund. It will likely take a mix of things to get you there. You don't have to get it done in a day, a month, or even a year. But once you have that emergency fund fully funded, you will feel better. What may be a catastrophe now will be a minor annoyance with a fully funded emergency fund. Finally, I'd recommend going to your bank and setting up a separate account for this emergency fund. A separate account specifically labeled as your emergency fund. This way you will think twice before spending it on a non-emergency.", "title": "" }, { "docid": "254572", "text": "From a budgeting perspective, the emergency fund is a category in which you've budgeted funds for the unexpected. These are things that weren't able to be predicted and budgeted for in advance, or things that exceeded the expected costs. For example you might budget $150 per month for car maintenance, and typically spend some of it while the rest builds up over time for unexpected repairs, so you have a few hundred available for that. But this month your transmission died and you have a $3,000 bill. You'll then fund most of this out of your emergency fund. This doesn't cover where to store that money though, which leads me to my next point. Emergencies are emergencies because they come without warning, without you having a chance to plan. Thefore the primary things you want in an emergency fund account are stability and quick access. You can structure investments to be whatever you think of as safe or stable but you don't want to be thinking about whether it's a good time to sell when you need the money right now. But the bigger problem is access. When you need the funds on a weekend, holiday, anytime outside of market hours, you're not going to be able to just sell some stocks and go to an ATM. This is the reason why it's recommended to have these funds in a checking or savings account usually. The reason I mentioned the budgeting side first is because I wanted to point out that if you're budgeting well, most of the unexpected expenses you have should have been expected in a sense; you can still plan for something without knowing when or if it will happen. So in the example of a car repair, ideally you're already budgeting for possible repairs, if you own a home you're budgeting for things that would go wrong, budgeting for speeding tickets, for surprise out of pocket medical costs, etc. These then become part of your normal budget: they aren't part of the emergency fund anymore. The bright side about budgeting for something unexpected is that you know what that money is for, and do you likely also know how quickly you'll need it. For example you know if you have unexpected medical costs that happen very quickly, you're not likely you need a bag of cash on a moment's notice. So those last two points lead to the fact that your actual emergency fund, the dollars that are for things you simply could not foresee, will be relatively small. A few thousand dollars or so in most cases. If you've got things structured like this, you'll be happy to have a few grand available at a moment's notice. The bulk of the money you would use for other surprise expenses (or things like 6 months of living expenses) is represented in other specific categories and you already know the timeframe in which you need it (probably enough time that it could be invested, risk to taste). In short: by expecting the unexpected, you can sidestep this issue and not worry so much about missed returns on the emergency fund.", "title": "" }, { "docid": "199971", "text": "\"For me, the emergency fund is meant to cover unexpected, but necessary expenses that I didn't budget for. The emergency fund allows me to pay for these things without going into debt. Let's say that my car breaks down, and I don't have any money in my budget for fixing it. I really need to get my car fixed, so I spend the money from my emergency fund. However, cars break down periodically. If I was doing a better job with my budget, I would allocate some money each month into a \"\"car repair/maintenance\"\" category. (In fact, I actually do this.) With my budgeting software, I can look at how much I've spent on car repairs over the last year, and budget a monthly amount for car repair expenses. Even if I do this, I might end up short if I am unlucky. Emergency fund to the rescue! If I'm budgeting correctly, I don't pay any regular bills out of this fund, as those are expected expenses. Car insurance, life insurance, and property tax are all bills that come on a regular basis, and I set aside money for each of these each month so that when the bill comes, I have the money ready to go. The recommended size of an emergency fund is usually listed as \"\"3 to 6 months of expenses.\"\" However, that is just a rough guideline. As you get better with your budget, you might find that you have a lower probability of needing it, and you can let your emergency fund fall to the lower end of the guideline range. The size of my own emergency fund is on the lower end of this scale. And if I have a true crisis (i.e. extended unemployment, severe family medical event), I can \"\"rob\"\" one of my other savings funds, such as my car replacement fund, vacation fund, etc. Don't be afraid to spend your emergency fund money if you need it. If you have an unexpected, necessary expense that you have not budgeted for, use the emergency fund money. However, your goal should be to get to the point where you never have to use it, because you have adequately accounted for all of the expenses that you can reasonably expect to have in the future.\"", "title": "" }, { "docid": "277529", "text": "\"If you think about it, it's really all one big pot of money. The idea behind an \"\"emergency fund\"\" is that you want to make sure your financial life has stability: it's not going to be suddenly driven into the red, below $0. As long as that doesn't happen, you can figure out how to live your life as you want. The reason we separate out an \"\"emergency fund\"\" is to simplify decision making. In theory, every single purchase you make should include a consideration of how it destabilizes you. Every $100 you spend on groceries is $100 you won't be able to bring to bear if you get fired or have a major accident. In practice, this would be a crippling way of thinking about things. You don't know what emergencies can hit you, nor when they will hit. That's why they're \"\"emergencies.\"\" If you had to think about them all the time, it'd be horrible! You would end up simply not thinking about it (like most people), and then the emergency hits when you don't have enough cash to stay solvent. The purpose of an \"\"emergency fund\"\" is to help make these decisions easier. If you have money set aside for \"\"emergencies\"\" that you only have to think about every now and then, you can make the decisions in the rest of your financial life without too much concern for them. You don't have to worry about that $100 in groceries because you are confident that if an emergency hits, that $100 won't be the straw that broke the camel's back because you have reserves to draw on. So you should define an \"\"emergency fund\"\" in a way which is most helpful for you to remain stable and solvent without having to fret about it too much. For most people, the criteria for tapping that fund is very high, because the goal is to not have to think about it all that much. If you wanted to, you could feel free to lump those \"\"medium predictability\"\" items into the emergency fund, but it just means you have to spend more time and effort thinking about the state of the fund. Every medium predictability purchase has to come with the thought process \"\"what is the state of the emergency fund? Could this purchase meaningfully destabilize my ability to handle emergencies?\"\" Your emergency fund might yo-yo under these extra purchases, which could force you to think about the state of your emergency fund for normal purchases. That'd be bad. Different people might want to think about things different ways. I'm a big-picture guy, so I prefer to think about all of my assets as one big account when I make a lot of my decisions. My wife, on the other hand, prefers not to have to think that way when she makes her purchases. For her, having a very discrete \"\"emergency fund\"\" has great value. For me, it has less. So when I look at the finances, I choose to lump the emergency funds in with, say, the funds to re-do our backyard (something we are looking at doing over the next 2-5 years). For me, that is the most natural way to deal with analyzing the risks -- I just have to be aware of how backyard purchases interact with our safety net. My wife prefers to keep those funds separate in her head, so that she can look at how to spend money on the backyard without thinking about how it affects our emergency readiness. While complicated, it shows that even within a household, it's possible to think about emergency funding two different ways. (it causes minimal headaches, though a fair bit of book-keeping) So define \"\"emergency fund\"\" however suits you and your life best. However, practically speaking, most people find it desirable to not put those medium predictability purchases into the same bucket as emergencies. Those that do find it desirable to put them in the same bucket typically have a personal reason for why that suits their needs better.\"", "title": "" }, { "docid": "451501", "text": "Is my financial status OK? If not, how can I improve it? I'm going to concentrate on this question, particularly the first half. Net income $4500 per month (I'm taking this to be after taxes; correct me if wrong). Rent is $1600 and other expenses are up to $800. So let's call that $2500. That leaves you $2000 a month, which is $24,000 a year. You can contribute up to $18,000 a year to a 401k and if you want to maintain your income in retirement, you probably should. The average social security payment now is under $1200. You have an above average income but not a maximum income. So let's set that at $1500. You need an additional income stream of $900 a month in retirement plus enough to cover taxes. Another $5500 for an IRA (probably a Roth). That's $23,500. That leaves you $500 a year of reliable savings for other purposes. Another $5500 for an IRA (probably a Roth). That's $23,500. That leaves you $500 a year of reliable savings for other purposes. You are basically even. Your income is just about what you need to cover expenses and retirement. You could cover a monthly mortgage payment of $1600 and have a $100,000 down payment. That probably gets you around a $350,000 house, although check property taxes. They have to come out of the $1600 a month. That doesn't seem like a lot for a Bay area house even if it would buy a mansion in rural Mississippi. Perhaps think condo instead. Try to keep at least $15,000 to $27,000 as emergency savings. If you lose your job or get stuck with a required expense (e.g. a major house repair), you'll need that money. You don't have enough income to support a car unless it saves you money somewhere. $500 a year is probably not going to cover insurance, parking, gas, and maintenance. It's possible that you could tighten up your expenses, but in my experience, people are more likely to underestimate their expenses than overestimate. That's why I'm saying $2500 (a little above the high end) rather than $2000 (your low end estimate). If things are stable, wait a year and evaluate. Track your actual spending. Ask yourself if you made any large purchases. Your budget should include an appliance (TV, refrigerator, washer/dryer, etc.) a year. If you're not paying for that now (included in rent?), then you need to allow for it in your ownership budget. I do not consider an ESPP to be a reliable investment vehicle. Consider the Enron possibility. You wake up one day and find out that there is no actual money. Your stock is now worthless. A diversified portfolio can survive this. If you lose your job and your investment, you'll be stuck with just your savings. Hopefully you didn't just tie them up in a house that you might have to sell to take your next job in a different location. An ESPP might work as savings for the house. If something goes wrong, don't buy the house. But it's not retirement or emergency savings. I would say that you are OK but could be better. Get your retirement savings started. That does two things. One, it gives you money for retirement. Two, it keeps you from having extra money now when it is easy to develop expensive habits. An abrupt drop from $4500 in spending to $1200 will hurt. A smooth transition from $2500 to $2500 is what you would like to see. You are behind now, but you have the opportunity to catch up for a few years. Work out how much you'll get from Social Security and how much you need to cover your typical expenses with the occasional emergency. Expect high health care costs in retirement. Medicare covers a lot but not everything, and health care is only getting more expensive. Don't forget to assume higher taxes in the future to help cover that expense and the existing debt. After a few years of catch up contributions, work out your long term plan assuming a reasonable real (after inflation) rate of return. If you can reduce the $23,500 in retirement contributions then, that's OK. But be pessimistic. Most people overestimate good things and underestimate bad things. It's much better to have extra than not enough. A 401k comes with an administrator and your choice of mutual funds. Try for diversification. Some money in bonds (25% to 30%). The remainder in stocks. Look for index funds. Try for a mix of value and growth, as they'll do better at different times. As you approach retirement, you can convert some of that into shorter term, lower yield investments. The rough rule of thumb is to have two to five years of withdrawals in short term investments like money market funds. But that's more than twenty years off. You have more choices with an IRA. In particular, you can choose your own administrator. But I'd keep the same stock/bond mix and stick to index funds if you're not interested in researching the more complex options. You may want to invest your IRA in a growth fund and your 401k in value funds and bonds. Then balance the stock/bond mix across both. When you invest each year, look at the underrepresented funds and add the most to them. So if bonds had a bad year and didn't keep pace, invest in bonds. They're probably cheap. You don't want to rebalance frequently, but once a year might be a good pace. That's about how often you should invest in an IRA, so that can be a good time. I'll let the others answer on the financial advisor part.", "title": "" }, { "docid": "439617", "text": "I think it's wise to account for those inevitable but unpredictable expenses like car/house repairs and abnormal medical bills when deciding on your emergency fund amount. So if you average $100/month for car repairs, and you have a 6-month emergency fund, then part of that fund is $600 for car repairs. If your total annual out of pocket for health insurance is $5,000/year, then emergency fund gets $2,500 and so on. This way, you add cushion to your emergency fund to handle those unpredictable but inevitable expenses without setting up a bunch of separate accounts. It doesn't have to be inflexible either, I know my furnace and air conditioner are way past their expected life, so I'm keeping a larger than normal emergency fund. Ultimately it's personal preference, to me, cash is all the same no matter what account it's in, but other people do best by keeping some logical/physical separation of funds intended for different purposes.", "title": "" }, { "docid": "64453", "text": "I'd be concerned about using CDs (or other non-liquid source) for your emergency fund because you become likely to use debt instead of tapping your emergency fund because you are worried about penalties (which typically only affect interest). This mind set can make you loan the bank money at 1-2% (buy a cd) and borrow money from the bank at 18-25% (credit card). Don't create psychological barriers to using your emergency fund in a true emergency Also, you recommend 3-8 months of expenses. The purpose of an emergency fund is to cover both a loss of income for 3-8 months, or a one time large expense (new roof, new sewer pipe to the house, etc.). A tiered solution solves the loss of income solution, but does not readily address the need for a one time, large emergency. I'd keep all of your emergency fund liquid.", "title": "" }, { "docid": "132839", "text": "\"First check: Do you have all the insurances you need? The two insurances everyone should have are: Another insurance you might want to get is a contents insurance (\"\"Hausratsversicherung\"\"). But if you don't own any super-expensive furniture or artworks, you might also opt to self-insure and cover it with: Priority 2: Emergency fund. Due to the excellent healthcare and welfare system in Germany, this is not as important as in many other countries. But knowing that you have a few thousand € laying around in liquid assets in case something expensive breaks down can really help you sleep at night. If you decide not to pay for contents insurance, calculate what it would cost you if there is a fire in your apartment and you would have to replace everything. That's how large your emergency fund needs to be. You also need a larger emergency fund if you are a homeowner, because as a homeowner there might always be an emergency repair you have to pay for. Priority 3: Retirement. Unless there will be some serious retirement reforms in the next 40 years (and I would not bet on that!), the government-provided pension will not be enough to cover your lifestyle cost. If you don't want to suffer from poverty as a senior citizen you will have to build up a retirement plan now. Check which options your company provides (\"\"Betriebliche Altersvorsorge\"\") and what retirement options you have which give you free money from the government (\"\"Riester-Rente\"\"). Getting professional advise to compare all the options with each other can be really beneficial. Priority 4: Save for a home. In the long-run, owning a home is much cheaper than renting one. Paying of a mortgage is just like paying rent - but with the difference that the money you pay every month isn't spent. Most of it (minus interest and building maintenance costs) stays your capital! At one point you will have paid it off and then you never have to pay rent in your life. It even secures the financial future of your children and grandchildren, who will inherit your home. But few banks will give you a good interest rate if you have no own capital at all. So you should start saving money now. Invest a few hundred € every month in a long-term portfolio. You might also get some additional free money for this purpose from your employer (\"\"Vermögenswirksame Leistungen\"\").\"", "title": "" }, { "docid": "487739", "text": "\"The concept of emergency fund is a matter of opinion. I can tell you the consensus is that one should have 6-9 months worth of expenses kept as liquid cash. This is meant to cover literally all bills that you might encounter during that time. That's a lot of money. There are levels of savings that are shy of this but still responsible. Not enough to cover too much in case of job loss, but enough to cover the busted transmission, the broken water heater, etc. this is still more than many people have saved up, but it's a worthy goal. The doctor visit is probably the lowest level. Even without insurance, the clinic visit should be under $200, and this shouldn't cause you to have to carry that amount beyond the time the bill comes in. The point that shouldn't be ignored is that if you owe money at 18% on a credit card, the emergency fund is costing you money, and is a bit misguided. I'd send every cent I could to the highest rate card and not have more than a few hundred $$ liquid until the cards were at zero. Last - $5K, $10K in the emergency account is great, unless you are foregoing matched 401(k) dollars to do it. All just my opinion. Others here whom I respect might disagree with parts of my answer, and they'd be right. Edit - Regarding the 'consensus 6-9 months' I suggest - From Investopedia - \"\"...using the conservative recommendation to sock away eight months’ worth of living expenses....\"\" The article strongly support my range for the fact that it both cites consensus, yet disagrees with it. From Money Under 30 The more difficult you rank your ability to find a new job, the more we suggest you save — up to a year’s worth of expenses if you think your income would be very difficult to replace. From Bank of America I have no issue with those comfortable with less. A dual income couple who is saving 30% of their income may very well survive one person losing a job with no need to tap savings, and any 'emergency' expense can come from next month's income. That couple may just need this month's bills in their checking account.\"", "title": "" }, { "docid": "426269", "text": "\"You are not wrong - just about anything can be charged and paid off in 30 days with a sale of non-liquid investments. So there are not any emergencies I can think of that require completely liquid funds (cash). For me, the risks are more behavioral than financial: I'm not saying it's a ridiculous, stupid idea, and these are all \"\"what-if\"\"s that can be countered with discipline and wise decisions, but having an emergency fund in cash certainly makes all of this simpler and reduces risk. If you have investments that you would have no hesitation liquidating to cover an emergency, then you can make it work. For most people, the choice is either paying cash, or charging it without having investment funds to pay it off, and they're back in the cycle of paying minimum payments for months and drowning in debt.\"", "title": "" }, { "docid": "85003", "text": "\"I'd lean toward using the $3,000 from the emergency fund although depending on your monthly bills, a $2,000 emergency fund (or even a $5,000 one) may be a bit small. But here are a couple of other options for you: Zero-interest balance transfers: If you have cards and have a zero balance on them, your credit card companies are keen to see you put a balance on them. Find out if they're offering any \"\"12 months no interest on balance transfers\"\" offers (or if any of their rivals is), since of course the car loan is an outstanding balance you can transfer (you're not asking them for cash). Put the $3,000 on that zero-balance transfer option, get rid of the car, and pay the $300/mo to pay down the balance on the card. 10 months later, two months before the end of the free period, you're at zero again — without dipping into your emergency fund. You'll also now have a history with that card company of paying back, which may lead them to attempt to entice you to go into more debt (which you'll resist, of course) by increasing the limit. (If you don't want a higher limit, just tell them to reduce it again.) A $3,000 unsecured loan with no pre-payment penalty provided the math works out. The interest may be expensive (unless you find something with a teaser rate for the first X months), but if you find an option, do the math on it to see if it's actually more expensive than carrying the car payments, insurance, etc. on a depreciating asset. It may not be as expensive as the 20% rate or whatever makes it sound (but again, do the math), and if you apply your $300/mo to it, within (say) 11 months you're clear again — with a nice little paid-back loan on your credit report. Both of these ensure that you still have your emergency fund at your disposal, and both capitalize on the fact that right now, you're probably a good credit risk. If you dip into your emergency fund, and an emergency happens (like loss of a job) and you find yourself short of funds, you may have trouble securing further credit at that point to cover the gap in your emergency fund.\"", "title": "" }, { "docid": "438571", "text": "I would suggest that you use Emergency Funds for things that have a Low likelihood of happening but if they do happen can be devastating. I used to work as a financial advisor and the sugfestion we gave people is to have about 3 months worth of expenses in cash. This was primarily to cover things luke loss of work or some unforseen even that would prevent you from missing work for an extended period of time. Once you have your emergency fund saved do not touch it! Leave it where it is. Then tou can start working on a savings account for those items that are more likely to happen but dont have as much of a negative impact.", "title": "" }, { "docid": "497993", "text": "Duffbeer703 covers most everything. The entire point of an emergency fund IS for it to be liquid. Now I do understand (if you feel your situation requires over 6 months of living expenses): That is a lot of money to have sitting in a statement savings account! Under no circumstances should you take any sort of risk with an emergency fund. However, you COULD do this: Invest some of the assets in a six month, 1 year or 2 year CD if returns were enough to be worthwhile. If you don't need the money, then fine, great. But if you do, you can break a Certificate of Deposit before maturity. There will be a penalty fee. You might lose interest too. But you'll have access to your money, no liquidity risk. So maybe you could put most, say 60% of your rainy day funds in truly liquid assets. The remainder could be in longer term CD's which you hopefully won't need because you'll be back to non rainy day living again.", "title": "" }, { "docid": "489480", "text": "You will find lots of rules of thumb but there is no universal truth to how much you should save. There are factors you DO need to consider though: you should start as early as possible to set money aside for retirement. You should then use a retirement calculator to at least get an understanding of the amount you need to set aside each month to achieve the desired retirement income; your default should be not to spend money and only spend money when you must. Leisure, travel and eating out should come last after you have saved up; you should have funds for different terms. For example, my wife and I have an emergency fund for unexpected expenses or losses in income. The rule of thumb here generally is to have 3-6 months of salary saved up. A longer term fund should be created for larger expenses like buying a car or preparing the cashdown on a property. Finally, the retirement fund which should cover your needs after you have retired.", "title": "" }, { "docid": "386305", "text": "Thank you for your service. My first suggestion since your car is a planned for the near future is keep that amount in savings and just pay cash. There are plenty of attractive offers to entice you to finance your vehicle but there really is no compelling reason to do it considering the savings you have. Second I would keep an additional portion of savings as a rainy day emergency fund. How much is based mostly on what you feel comfortable with. The number of possible emergencies that can come up is limited and your expenses are limited which is normal given your age. This fund might be for something such as emergency travel for a sick family member, cover a deductible for an auto accident, whatever unforseen event might occur (hence the name emergency fund). What investments you are comfortable with will be determined by risk tolerance. While in the military individual stocks that are aggressive risky investments may not be a good idea because of the extra attention they require and you can't really babysit a portfolio while deployed but there are many good low or no cost mutual funds or ETFs that you could get into. I would look into setting up a recurring purchase with a set dollar amount monthly so you will continue to accumulate whatever option you are investing in regularly even if you are deployed. Which fund or ETF you pick will depend on your goals and risk tolerance but you could very easily pick several for diversity. Good luck and thank you again for your service.", "title": "" }, { "docid": "149367", "text": "\"If you have wage income that is reported on a W2 form, you can contribute the maximum of your wages, what you can afford, or $5500 in a Roth IRA. One advantage of this is that the nominal amounts you contribute can always be removed without tax consequences, so a Roth IRA can be a deep emergency fund (i.e., if the choice is $2000 in cash as emergency fund or $2000 in cash in a 2015 Roth IRA contribution, choice 2 gives you more flexibility and optimistic upside at the risk of not being able to draw on interest/gains until you retire or claim losses on your tax return). If you let April 15 2016 pass by without making a Roth IRA contribution, you lose the 2015 limit forever. If you are presently a student and partially employed, you are most likely in the lowest marginal tax rate you will be in for decades, which utilizes the Roth tax game effectively. If you're estimating \"\"a few hundred\"\", then what you pick as an investment is going to be less important than making the contributions. That is, you can pick any mutual fund that strikes your fancy and be prepared to gain or lose, call it $50/year (or pick a single stock and be prepared to lose it all). At some point, you need to understand your emotions around volatility, and the only tuition for this school is taking a loss and having the presence of mind to examine any panic responses you may have. No reason not to learn this on \"\"a few hundred\"\". While it's not ideal to have losses in a Roth, \"\"a few hundred\"\" is not consequential in the long run. If you're not prepared at this time in your life for the possibility of losing it all (or will need the money within a year or few, as your edit suggests), keep it in cash and try to reduce your expenses to contribute more. Can you contribute another $100? You will have more money at the end of the year than investment choice will likely return.\"", "title": "" }, { "docid": "574654", "text": "I would say that, for the most part, money should not be invested in the stock market or real estate. Mostly this money should be kept in savings: I feel like your emergency fund is light. You do not indicate what your expenses are per month, but unless you can live off of 1K/month, that is pretty low. I would bump that to about 15K, but that really depends upon your expenses. You may want to go higher when you consider your real estate investments. What happens if a water heater needs replacement? (41K left) EDIT: As stated you could reduce your expenses, in an emergency, to 2K. At the bare minimum your emergency fund should be 12K. I'd still be likely to have more as you don't have any money in sinking funds or designated savings and the real estate leaves you a bit exposed. In your shoes, I'd have 12K as a general emergency fund. Another 5K in a car fund (I don't mind driving a 5,000 car), 5k in a real estate/home repair fund, and save about 400 per month for yearly insurance and tax costs. Your first point is incorrect, you do have debt in the form of a car lease. That car needs to be replaced, and you might want to upgrade the other car. How much? Perhaps spend 12K on each and sell the existing car for 2K? (19K left). Congratulations on attempting to bootstrap a software company. What kind of cash do you anticipate needing? How about keeping 10K designated for that? (9K left) Assuming that medical school will run you about 50K per year for 4 years how do you propose to pay for it? Assuming that you put away 4K per month for 24 months and have 9K, you will come up about 95K short assuming some interests in your favor. The time frame is too short to invest it, so you are stuck with crappy bank rates.", "title": "" }, { "docid": "355240", "text": "\"In your comment, you said: It just seems a little stupid to me to go and put away money for the explicit purpose of emergencies (presumably in a way that's somehow different from how you would normally save money). Seems better to go and treat the money as you would normally, and then pull whatever you need from the money that you had saved. The problem with that logic is that people save money for many different things. You might save for a vacation, or a new refrigerator, or a new car, or a house, or your kids' college education. If you \"\"pull whatever you need\"\" for such expenses, you may find that when a real emergency occurs, you don't have enough money. The things you used it for may have been legitimate, reasonable expenses, but nonetheless you may later wish you had deferred those expenses until after you had built up a cushion. So the idea of an emergency fund is to designate certain money that is not to be used for \"\"whatever you need\"\", but specifically for unforeseen circumstances. Of course there can be debate about what counts as an emergency, but the main point is to distinguish saving for planned future expenses from saving for unplanned future expenses. Note that this doesn't mean the money has to be in a separate account, or saved in any special \"\"way\"\". It just means the money has to be considered by you as an emergency fund. For some people, it may be psychologically useful to put the emergency fund in a separate account that they never withdraw from. But even if you just have all your money in one savings account and you mentally tell yourself, \"\"I don't want to ever let the balance drop below $10,000, just so I have a safety cushion\"\" then you are effectively designating that $10,000 as an emergency fund.\"", "title": "" }, { "docid": "244692", "text": "\"One can generalize on Traditional vs Roth flavors of accounts, I suggest Roth for 15% money and going pretax to avoid 25% tax. If the student loan is much over 4%, it may make sense to put it right after emergency fund. For emergency fund priority - I'm assuming EF really requires 2 phases, the $2500 broken transmission/root canal bill, and the lose your job, or need a new roof level bills. I'm in favor of doing what let's you sleep well. I'm also quick to point out that if you owe $2500 at 18%, yet have $2500 in your emergency fund, you're really throwing away $450 in interest each year. There's an ongoing debate of \"\"credit card as emergency fund.\"\" No, I don't claim that your cards should be considered an emergency fund, per se, but I would prioritize knocking off the 18% debt as a high priority. Once that crazy interest debt is gone, fund the ER, and find a balance for savings and the next level ER, the 6-9mo of expenses one. One can choose to fund a Roth IRA, but keep the asset out of retirement calculations. It's simply an emergency account returning tax free interest, and if never used, it eventually is retirement money. A Roth permits withdrawal of deposited funds with no tax or penalty, just tracking it each year. This actually rubs some people the wrong way as it sounds like tapping your retirement account for emergencies. For my purpose, it's a tax free emergency fund. Not retirement, unless and until you are saving so much in the 401(k) you need more tax favored retirement money. I wrote an article some time ago, the Roth Emergency Fund which went into a bit more detail. Last - keep in mind, this is my opinion. I can intelligently argue my case, but at some point, it's up to the individual to do what feels right. Paying 18% debt off a bit slower, say 4 years instead of 3, in favor of funding the matched 401(k), to me, you run the numbers, watch the 401(k) balance grow by 2X your pretax deposits, and see that in year 3, your retirement account is jump-started and far, far more than your remaining 18% cards. Those who feel the opposite and wish to be debt free first are going to do what they want. And the truth is, if this lets you sleep better at night, I'm in favor of it.\"", "title": "" }, { "docid": "192811", "text": "\"First, don't save anything in a tax sheltered vehicle. You will be paying so little tax that there will be essentially no benefit to making the contributions, and you'll pay tax when they come out. Tax free compounding for 40 years is terrific, but start that after you're earning more than a stipend. Second, most people recommend having a month's expenses readily available for emergencies. For you, that would be $1500. If you put $100 a month aside, it will take over a year to have your emergency fund. It's easy to argue that you should pick a higher pace, so as to have your emergency money in place sooner. However, the \"\"emergencies\"\" usually cited are things like home repair, car repair, needing to replace your car, and so on. Since you are renting your home and don't have a car, these emergencies aren't going to happen to you. Ask yourself, if your home was destroyed, and you had to replace all your clothes and possessions (including furniture), how much would you need? (Keep in mind any insurance you have.) The only emergency expense I can't guess about is health costs, because I live in Canada. I would be tempted to tell you to get a credit card with a $2000 limit and consider that your emergency fund, just because grad student living is so tight to the bone (been there, and 25 years ago I had $1200 a month, so it must be harder for you now.) If you do manage to save up $1500, and you've really been pinching to do that (walking instead of taking the bus, staying on campus hungry instead of popping out to buy food) let up on yourself when you hit the target. Delaying your graduation by a few months because you're not mentally sharp due to hunger or tiredness will be a far bigger economic hit than not having saved $200 a month for 2 or 3 years. The former is 3-6 months of your new salary, the latter 5-7K. You know what you're likely to earn when you graduate, right?\"", "title": "" }, { "docid": "120706", "text": "I like the way you framed this question. There is no single right answer for what to do with your savings, but there are some choices that are wrong in the sense that they are dominated by other choices you could make. Of the choices you listed, there are two that fall into that category. The ones that seem like a bad idea to me are: Putting it into your Roth 401(k). You can't do this directly anyhow, but you could do it indirectly by increasing your contributions and using the growth fund to cover the hole in your budget, but that's a lot of work for a relatively small gain. You would essentially be exchanging one long-term investment for another long-term investment. You would pay capital gains taxes on the investment when you sell it today, in order to not pay taxes on its earnings when you eventually withdraw it. There is some benefit there, but it's a long way off, not that large, and probably not worth the effort. Things that might change your mind: If your 401(k) was a traditional 401(k) (paying tax at capital gains rate today to get a deduction at your normal income rate is likely to be a win). You're not contributing enough to get the full company match (always try to get that match if you can). Putting it into your emergency fund. Once again, you are likely to pay capital gains tax if you do this, and you will be putting it into an investment that is likely to get a lower return than your current one. It isn't really necessary to incur these costs, since if you encounter an emergency that you can't cover with your existing emergency fund, you could always liquidate the growth fund then, when you know you need it. Now, a growth fund is going to be more volatile than what you would normally want for an emergency fund, but the risk isn't that bad, if you think about it. Say your emergency comes up and you find that the growth fund is down 20% (which would be a pretty horrible run). That's $600 less that you have to deal with the situation. Keep in mind that you already have $2000 (and building) in your current emergency fund. Is that $600 going to make the difference between meeting the need and not? It's not likely. Better to leave the investment where it is and keep building your emergency fund week by week. Things that might change your mind: Your level of risk aversion (if having that money in a more risky investment is keeping you up at night, move it). You face significant job uncertainty (if you have reason to think your job is at risk, it might be a good idea to top off that emergency fund sooner rather than later.) Your other two choices both seem like solid options under the right circumstances. If it were me, I'd leave the investment in place rather than use it to pay off the student loan. The investment is likely (though of course not guaranteed) to earn more than the interest rate even on the highest-rate loan, especially when you consider that the interest on the student loan is probably tax deductible. Moreover, the size of the investment isn't enough to fully repay the loan, so putting it toward the loan won't even improve your cash flow for some time to come. However, there is always a chance that the investment will perform poorly and some people prefer the guaranteed return from paying off the loan. It depends on your personal risk tolerance. The one thing I would recommend is to think of putting the money toward the loan not as a debt repayment, but as a fixed-income investment with a yield equal to your loan's interest rate. If you would still consider buying it then, then go ahead. If not, then stick with what you've got. In my experience people get way too emotional about debt; try to take that emotion out of your decision making if you can.", "title": "" }, { "docid": "178303", "text": "\"Some thoughts: 1) Do you have a significant emergency fund (3-6 months of after-tax living expenses)? If not, you stand to take a significant loss if you have an unexpected need for cash that is tied up in investments. What if you lose/hate your job or your car breaks down? What if a you want to spend some time with a relative or significant other who learns they only have a few months to live? Having a dedicated emergency fund is an important way to avoid downside risk. 2) Lagerbaer has a good suggestion. Given that if you'd reinvested your dividends, the S&P 500 has returned about 3.5% over the last 5 years, you may be able to get a very nice risk-free return. 3) Do you have access to employer matching funds, such as in a 401(k) at work? If you get a dollar-for-dollar match, that is a risk-free pre-tax 100% return and should be a high priority. 4) What do you mean by \"\"medium\"\" volatility? Given that you are considering a 2/3 equity allocation, it would not be at all out of the realm of possibility that your balance could fall by 15% or more in any given year and take several years to recover. If that would spook you, you may want to consider lowering your equity weights. A high quality bond fund may be a good fit. 5) Personally, I would avoid putting money into stocks that I didn't need back for 10 years. If you only want to tie your money up for 2-5 years, you are taking a significant risk that if prices fall, you won't have time to recover before you need your money back. The portfolio you described would be appropriate for someone with a long-term investment horizon and significant risk tolerance, which is usually the case for young people saving for retirement. However, if your goals are to invest for 2-5 years only, your situation would be significantly different. 6) You can often borrow from an investment account to purchase a primary residence, but you must pay that amount back in order to avoid significant taxes and fees, unless you plan to liquidate assets. If you plan to buy a house, saving enough to avoid PMI is a good risk-free return on your money. 7) In general, and ETF or index fund is a good idea, the key being to minimize the compound effect of expenses over the long term. There are many good choices a la Vanguard here to choose from. 8) Don't worry about \"\"Buy low, sell high\"\". Don't be a speculator, be an investor (that's my version of Anthony Bourdain's, \"\"don't be a tourist, be a traveler\"\"). A speculator wants to sell shares at a higher price than they were purchased at. An investor wants to share in the profits of a company as a part-owner. If you can consistently beat the market by trying to time your transactions, good for you - you can move to Wall Street and make millions. However, almost no one can do this consistently, and it doesn't seem worth it to me to try. I don't mean to discourage you from investing, just make sure you have your bases covered so that you don't have to cash out at a bad time. Best of luck! Edit Response to additional questions below. 1) Emergency fund. I would recommend not investing in anything other than cash equivalents (money market, short-term CDs, etc.) until you've built up an emergency fund. It makes sense to want to make the \"\"best\"\" use of your money, but you also have to account for risk. My concern is that if you were to experience one or more adverse life events, that you could lose a lot of money, or need to pay a lot in interest on credit card debt, and it would be prudent to self-insure against some of those risks. I would also recommend against using an investment account as an emergency fund account. Taking money out of investment accounts is inefficient because the commissions/taxes/fees can easily eat up a significant portion of your returns. Ideally, you would want to put money in and not touch it for a long time in order to take advantage of compounding returns. There are also high penalties for early disbursements from retirement funds. Just like you need enough money in your checking account to buy food and pay the rent every month, you need enough money in an emergency fund to pay for things that are a real possibility, even if they are less common. Using a credit card or an investment account is a relatively expensive way to do this. 2) Invest at all? I would recommend starting an emergency fund, and then beginning to invest for retirement. Once your retirement savings are on track, you can begin saving for whatever other goals you may have\"", "title": "" }, { "docid": "68239", "text": "The issue is how likely you will have zero income for six months, and what are your monthly expenses. If you know the maximum medical bill you face that may allow you to save a smaller amount. But you still have to protect for that loss of income. The interuption could be because of job loss, medical emergency, or other family crisis. If I told you that the chances you would face a crisis dropped by 50%, would you decide that the need for an emergency fund went away? Or would you still create a fund? I think the need still exists just to avoid the downside if you aren't prepared.", "title": "" }, { "docid": "122952", "text": "\"The guideline for the size of an emergency fund is just a guideline. I've usually heard it expressed as \"\"3 to 6 months,\"\" but everyone has a different idea of exactly how big it should be. The purpose of the fund is to give you enough cash to be able to pay for unexpected expenses that have come up that you have not budgeted for without you having to borrow money to pay for them. To figure out how big this fund should be, we look at the worst case scenario. Suppose that you lost your job tomorrow. What would you do? Cut your expenses. You'd probably be much more careful how you spend money. Secure health insurance. This would be done by either continuing your employer's policy with COBRA, or by purchasing your own insurance, likely through the Obamacare/ACA market. Keep in mind that most likely your employer is paying for a portion of your insurance now, so this expense will go up quite a bit no matter which option you choose. Look for another job. You'd probably begin your search for a new job immediately. The size of your emergency fund determines how long you will be able to go without income before you need to start a new job. Regarding cutting your expenses, it is up to you how much you would cut. There are things that are easy to cut temporarily (or permanently), such as restaurants, entertainment expenses, vacations, etc. You would probably stop retirement investing until you have income again. The more you cut, the longer your emergency fund would last. Things you don't want to cut are necessities, like housing, groceries, utilities, transportation, etc. I would also include health insurance in this list. Certainly, if you have a pre-existing condition, you do not want to let your health insurance coverage lapse. Your employability is also a factor. If you believe that you would have an easy time finding similar employment to what you have now, your emergency fund might not need to be quite as big as someone who believes they would have a harder time finding another job.\"", "title": "" } ]
2441	Is building a corporation a good option?	[ { "docid": "487870", "text": "Creating a corporation is not necessarily less taxes. In fact, you'll face the problem of double taxation, and since you must pay yourself a reasonable salary, if your corporation doesn't earn much to give you as dividend after the salary, and/or your tax bracket is low, you'll in fact may end up paying more taxes. Also there's a lot of bureaucracy involved in managing a corporation. Liability on the other hand is important, and what's more important - is asset separation and limiting the liability to the corporation assets, keeping your personal assets safe. To achieve that, you don't have to create a corporation, but you can create a Limited Liability Company (LLC). LLC are disregarded entities for tax purposes (i.e.: you won't have to pay taxes twice, only once as a sole proprietor/partner), but provide the liability limitation and asset separation. LLC's are much less formal, and require much less paperwork reducing the risk of corporate veil piercing because of non-compliance. I myself decided to manage my investments through LLC's for that very reason (asset separation).", "title": "" }, { "docid": "346374", "text": "Compared with a Sole Proprietorship, the main disadvantages of an S-Corporation or an LLC are that it adds a lot of management overhead (time, and possibly money if you don't do it all yourself), and there are fees you must pay to incorporate, as well as additional yearly maintenance fees which vary by state. You should be able to weigh the tax savings and liability protection against the extra costs and hassle, and see which way the scales tip. As a rule of thumb, the bigger your business gets or the more income you make, the more attractive incorporating becomes. Note there are some additional taxes that certain jurisdictions impose on business income. For example, IL and CA charge 1.5% tax, NY is less, but NYC is 8.85%! In NYC specifically, you could actually end up paying slightly more tax as an S-Corp than you would as a Sole Proprietorship. In most places though, the nominal local taxes will still be less than the FICA taxes you could potentially save.", "title": "" } ]	[ { "docid": "530902", "text": "\"I don't want to hate on those other comments but as a college student having a 4.0 and going to a \"\"target\"\" school are not realistic goals for everyone. The best advice I would give you is to be passionate about the field. It sounds dumb on its face but being involved in student investment clubs/funds or competing in investment competitions are great ways to get exposure and meet people in the field while building your resume. Internships are incredibly important because that's where you prove to yourself and others that you are a capable person. You also have a lot of options ahead of you. You can do research, client facing roles (CFP), and even corporate finance. I wasn't a finance major but I spent 3 years in college working in our student managed investment fund and it absolutely paid off (now doing corporate finance). You have to want to learn and grow. It's not realistic for a college student with limited resources to get your CFA level 1 or series exams, especially if it doesn't suit your field. Be open to different types of jobs and build relationships with your professors who are well connected. It does help to have stellar grades and it helps to be at a top school but our state school has put kids on the Street. You just have to be hungry and realistic about your talents and passion. Good luck to you.\"", "title": "" }, { "docid": "426677", "text": "\"Yeah, well, and corporations used to only be chartered by states for the express purpose of fulfilling some public function, on the order of building a bridge, etc. Now, anybody at all gets the limited liability advantages of a corporation without any of the corresponding duty to serve the public good. Now I'm sure the overall \"\"fix\"\" that will be floated will be the government basically dismantling capitalism and principles enjoyed by all private businesses, instead of just going back and fixing what was erroneously handed to corporations in the first place.\"", "title": "" }, { "docid": "144660", "text": "It is a good opportunity for those people who want to spend the vacation and make rememberable events, You should find the good rated great escapist team inside escape rooms. We have the fabulous event which is unforgetable services. It is good pleasure things for us that we get the chance to serve you. Escape rooms diversions as in Corporate team building escape rooms fort Lauderdale plan to test your critical thinking and analyst aptitudes. If you want to come here with your family, you can bring your family without hesitation. We provide the full security and corporate with our customers. There is no more place so beautiful and attractive.", "title": "" }, { "docid": "324531", "text": "Best for team building escape rooms WPB for your office colleagues and best friends for making an unforgettable memory with them by a top event planner in the West Palm Beach, Florida by the corporateteambuildingescaperooms for the corporate events. There are various things to do over here with your team and team building escape rooms WPB, You can choose best escape room, apart from this it is game where your team can build up trust and bond between with each other and let know them they can do good work better with each other your colleagues.", "title": "" }, { "docid": "274974", "text": "It is a good events here to get the full entertainment with our team building who gives you a target such as solving puzzles inside the escape rooms . There are more activity here for your special fun. The Escape Rooms Palm Beach is so amazing place in USA, Florida. It is so excellent place for the couple and many individuals comes here to get real entertainment that would help the teammates. We corporate events west palm beach with a team building.", "title": "" }, { "docid": "527090", "text": "\"When one says that \"\"corporations are people\"\", in a legal sense, they are saying that they have the ability to enter into binding legal agreements in a manner similar to people. This allows corporations to do things like own a building or a car, or enter into a contract. This is so that an individual does not have to do so. This keeps individuals from being liable for the activities of the corporation (it also keeps the individual from running off the the corporation's car or selling the corporation's building). If they are using it in any sense other than the legal sense, it's either hyperbole, ignorance, or pandering. Now, if you set yourself up as LettersFromTheSky, Inc, then you would very well be able to get all the same tax deductions and benefits as a corporation. But you would also be liable for everything that a corporation is liable for (namely, a higher standard of reporting and different accounting methods).\"", "title": "" }, { "docid": "483991", "text": "The finance sector is comprised of such enterprises as banks, investment funds, insurance companies and real estate. It is traditionally contrasted with what has been called the 'real economy' because funds created and utilized in this sector produce neither goods, services or fixed capital. The unproductive nature of transactions can easily be seen in such things as real estate. When a company undertakes to build a house or whatever its input goes directly to the labor and goods necessary for such a project. At its worst the financial sector mobilizes funds not just for production but for simple acquisition. Should a company raise the funds to buy an already existing building or the mortgage on same quite obviously nothing is produced. Same building on day one as when it was owned by another. That, of course, is an extreme example as are corporate takeovers via private equity. In that case the efforts of the financial sector are not just non-productive but are often in fact ''anti-productive'' as they destroy or prevent the use of real factors of production. This 'anti-productive' action was demonstrated on a massive global scale during the last financial crisis. The basically parasitic nature of the financial sector isn't always so blatant. There are some that argue that its 'services' can be valuable to the real economy. Perhaps, but that has to be determined on a case by case examination and while keeping the idea ''is there a better way to do this** in one's mind.", "title": "" }, { "docid": "154841", "text": "The short answer, probably not much. Unless you have a controlling interest in the company. If at least 50%+1 of the shareholder votes are in favor of the dilution then it can be done. There are some SEC rules that should protect against corporate looting and theft like what the Severin side is trying to make it appear as happened. However it would appear that Severin did something stupid. He signed away all of his voting right to someone who would use them to make his rights basically worthless. Had he kept his head in the game he could probably have saved himself. But he didn't. If your average startup started issuing lots of stock and devaluing existing shares significantly then I would expect it would be harder to find investors willing to watch as their investment dwindled. But if you are issuing a limited amount stock to get leverage to grow bigger then it is worth it. In the .com bubble there were quite a few companies that just issued stock to buy other companies. Eventually most of these companies got delisted because they diluted them selves to much when they were overvalued. Any company not just a startup can dilute its shares. Many if not most major companies issue stock to raise capital. This capital is then generally used to build the business further and increase the value of all shares. Most of the time this dilution is very minor (<.1%) and has little if any impact on the stock. There are rules that have to be followed as listed companies are regulated by the SEC. There are less regulations with private corporations. It looks like the dilution was combined with the buyout of the Florida company which probably contributed to the legality of the dilution. With options they are generally issued at a set price. This may be higher or lower than the reported sell price of the stock when the option is issued. The idea is over time the stock will increase in value so that those people who hold on to their options can buy the stock for the price listed on the option. I worked at an ISP start up in the 90's that made it pretty well. I left before the options were issued but I had friends still there that were issued an option at $16 a share the value of the stock at the time of the issue of the option was about 12. Well the company diluted the shares and used them to acquire more ISP's unfortunately this was about the time that DSL And cable internet took off so the dial up market tanked. The value eventually fell to .10 they did a reverse split and when they did the called in all options. The options did not have a positive cash value at any time. Had RMI ever made it big then the options could have been worth millions. There are some people from MS and Yahoo that were in early that made millions off of their options. This became a popular way for startups to attract great talent paying peanuts. They invested their time in the business hoping to strike gold. A lot of IT people got burned so this is less popular among top talent as the primary compensation anymore.", "title": "" }, { "docid": "174016", "text": "They will just break the company up into subsidiaries. A smaller company will run the mail room, another will run the computer repair, yet another will run the sales team and so on an so forth. There will be one small executive company that runs all those companies and siphons all the revenue from all of the subsidiaries. Using your scheme they can make you a 30% owner of a subsidiary that services another subsidiary and makes no money at all and in fact is a money loser and stock options will mean nothing. Major motion pictures do something similar: each movie is its own entity/company, lets call it BigExpensiveMovie397 Co., that is only around for a single movie. BigExpensiveMovie397 then hires other companies to do the work: catering, set building, production and everything else that makes a movie. And here is the fun part: if BigExpensiveMove397 is a hit, then it will pay a lot of licensing fees to yet other corporations that allowed it the use of its characters, story and anything else they can think of. Those licensing fees tend to always be more that whatever profit BigExpensiveMove397 makes. And that is how movies like LOTR is a money loser...no matter how much money it makes. Which is why the convinced Congress to ban using actual money with HSX... There is no way to beat such accounting. The only choice is not to take jobs like that. But since we are competing with the World and a good annual salary is $6K a year....we have a long way to go down to hit equilibrium.", "title": "" }, { "docid": "399885", "text": "\"Just as a matter of research, apparently there is a way to find high option volumes such as a site here: https://www.barchart.com/options/volume-leaders/stocks However, that information is going to be heavily skewed by \"\"underlying security that moved a lot more than expected and probably got a lot of positions filled incidentally today\"\", but I think it is a good place to start building up a list of securities with a lot of option interest. There is also a tab there for ETFs. This will not tell you exactly that a particular stock always has high option volume, but most of the ones that show up there repeatedly and across multiple strike prices will meet your criteria.\"", "title": "" }, { "docid": "502242", "text": "Get the perfect team to inspect the home before buying, it is a big investment to buy the house in a better place. In that case, we will help you. Now, no need to go anywhere in Australia. The Assured Building Inspections have wonderful experience of the inspection the building, now we are expert in this work. Always, we provide the affordable service for our clients. It is a mandatory procedure for each homeowner, we are a good protection organization inside the Australia. There is lots of inspection service company in Australia, however, they may be not proper certified in this work. It is one among most inspector and trustable corporation. We are specializing the most problems in property inspections and reports. Our impartial opinions, provide our clients with the self assurance and peace of thoughts they need to do properly knowledgeable.", "title": "" }, { "docid": "9161", "text": "What do you think happens when cash gets paid out to investors? People don't just collect the cash and stuff it in their mattress. They reinvest it, sometimes in other giant corporations, sometimes in start-ups, sometimes in government bonds. Some of it goes to fund R&D elsewhere, some of it goes to fund building bridges and roads, some of it goes toward buying houses. Ultimately, how much goes to each piece of the pie depends on the attractiveness of each opportunity. If there are a lot of good R&D projects that would generate good returns, people will invest in them.", "title": "" }, { "docid": "395759", "text": "This is the section that I was referring to: >We are unable to build bridges, we're unable to build airports, our inner city school kids are not graduating. >I was just in France, I was recently in Argentina, I was in Israel, I was in Ireland. We met with the prime minister of India and China. It's amazing to me that every single one of those countries understands that practical policies to promote business and growth is good for the average citizens of those countries, for jobs and wages, and that somehow this great American free enterprise system, we no longer get it. >Corporate taxation is critical to that, by the way. We've been driving capital earnings overseas, which is why there's $2 trillion overseas benefiting all these other countries and stuff like that. So if we don't get our act together — we can still grow.", "title": "" }, { "docid": "131117", "text": "Disclaimer: I don't work in the finance industry, and simply took a few classes in corporate finance and management during my undergrad. It depends on what type of investing you're talking about. If you're talking about building a portfolio of securities, then CAPM is the basis for most valuation models. Generally, CAPM will have you discount based on your best available risk-free rate (usually t-bills or some other fixed income source with a reliable backer). Even after your valuation, the basic theory of risk management for an investment portfolio is still to maintain a diverse basket of poorly correlated products. If you're talking about corporate finance where a firm is considering an investment such as a new project, then a determining a WACC and using it as a discount rate for your cash flow is a basic strategy. This is a basic strategy, but there are better ones depending on the specifics of the investment. This is where evaluating exposures is important. To hedge counterparty risk, you might discount by the estimated probability of non-payment or buy trade insurance. To hedge currency risk, you might buy forwards, options, or look into a money market hedge. To hedge political risks like repatriation or changes in tax laws or regulation you might buy political risk insurance. To hedge exposure to a particular commodity price, you can trade futures.", "title": "" }, { "docid": "149820", "text": "\"Corporate restructuring makes everything a flux, so you might as well revisit some core fundamental questions. Here's how to do this professionally: Start floating your CV now. Line up interviews in competing companies. Attend to them. Score a job offer, and have it put into writing, with exact salary, which should be at least 10%++ of your current one. Take a clear empty page, and write on top: \"\"Business value provided\"\". Put down your major contributions, and achievements. Wherever possible, put the company's expected dollar value near to it. For bonus points, sum it up on the bottom, and minus your current salary. Difference is \"\"Profit provided directly to the company's bottom line\"\". Float this to your manager's desk. At this position, you have only one fundamental question to your boss: \"\"match or pass?\"\" :) A corporate spin-off is a good time to do this: 1, to ensure, that your position will not be made redundant; 2, if it is, you have a backup plan. If the parent company's \"\"getting rid of you\"\", however, there are even more fundamental questions you might want to ask yourself: is this really a profitable division, or merely a loss leader? Does this company have a future, and the adequate growing options for you, personally? To answer these questions, you must have an opportunity cost estimation; and for that, you must have second (and preferably, third) options -hence, the strategy above. To conclude, the best time to do your job research is every other month; and the best time to ask for a raise is always now :) Good luck!\"", "title": "" }, { "docid": "66267", "text": "\"When I look at debt I try to think of myself as a corporation. In life, you have a series of projects that you can undertake which may yield a positive net present value (for simplicity, let's define positive net present value as a project that yields more benefit than its cost). Let's say that one of the projects that you have is to build a factory to make clothing. The factory will cost 1 million dollars and will generate revenue of 1.5 million dollars over the next year, afterwhich it wears out. Although you have the knowledge to build this wonderful factory, you don't have a million bucks laying around, so instead, you go borrow it from the bank. The bank charges you 10% interest on the loan, which means that at the end of the year, the project has yielded a return of 400k. This is an extremely simplified example of what you call \"\"good\"\" debt. It is good if you are taking the debt and purchasing something with a positive value. In reality, this should be how people should approach all purchases, even if they are with cash. Everything that you buy is an investment in yourself - even entertainment and luxury items all could be seen as an investment in your happiness and relaxation. If more people approached their finances in this way, people would have much more money to spend, William\"", "title": "" }, { "docid": "238474", "text": "If it helps you to think about it, long is equivalent to betting for the upside and short is equivalent to betting for the downside. If you are long on options, then you expect the value of such options to increase. If you are long an option, then you own the option. If you are short an option, then generally you sold the option. Someone who is short a call (sometimes called the writer or occasionally the issuer) has sold a call option to someone who is now long a call. Buying a call option that will increase in value is itself a form of investment, just as it's investment to buy stock or other instruments hoping they will appreciate in value. An option's value will rise or fall with the underlying, so being long an option is a way to be long in the underlying. Someone can be long in a stock by buying the stock, or long in a call by buying call options in the stock. The long call generally requires less initial investment than buying the underlying, and lets the option-holder avoid the asset downside during the option term. The risk is that the asset may not appreciate to the point that the call option will pay off. In the conceptual sense, a share of stock is a particular right to the profits and assets of a corporation, both in form of dividends and in liquidation. An option is a particular right to the the share of stock. It's just a further way to formalize and subdivide the various property rights that exist in a corporation. If you can buy a piece of paper with particular rights to corporate profits and assets, then you can buy another piece of paper with particular rights to the former piece of paper.", "title": "" }, { "docid": "111466", "text": "When you start living in US, it doesn't actually matter what was your Credit history in another country. Your Credit History in US is tied to your SSN (Social Security Number), which will be awarded once you are in the country legally and apply for it. Getting an SSN also doesn't guarantee you nothing and you have to build your credit history slowly. Opening a Checking or Savings account will not help you in building a credit history. You need to have some type of Credit Account (credit card, car loan, mortgage etc.) linked to your SSN to start building your credit history. When you are new to US, you probably won't find any bank that will give you a Credit Card as you have no Credit history. One alternative is to apply for a secured credit card. A secured credit card is one you get by putting money or paying money to a bank and open a Credit Card against that money, thereby the bank can be secure that they won't lose any money. Once you have that, you can use that to build up your credit history slowly and once you have a good credit history and score, apply for regular Credit Card or apply for a car loan, mortgage etc. When I came to US 8 years ago, my Credit History was nothing, even though I had pretty good balance and credit history back in my country. I applied for secured credit card by paying $500 to a bank ( which got acquired by CapitalOne ), got it approved and used it for everything, for three years. I applied for other cards in the mean time but got rejected every time. Finally got approved for a regular credit card after three years and in one year added a mortgage and car loan, which helped me to get a decent score now. And Yes, a good Credit Score is important and essential for renting an apartment, leasing a car, getting a Credit Card etc. but normally your employer can always arrange for an apartment given your situation or you need to share apartment with someone else. You can rent a car without and credit score, but need a valid US / International Drivers license and a Credit Card :-) Best option will be to open a secured credit card and start building your credit. When your wife and family arrives, they also will be assigned individual SSN and can start building their credit history themselves. Please keep in mind that Credit Score and Credit History is always individual here...", "title": "" }, { "docid": "293389", "text": "\"This is the sad state of US stock markets and Regulation T. Yes, while options have cleared & settled for t+1 (trade +1 day) for years and now actually clear \"\"instantly\"\" on some exchanges, stocks still clear & settle in t+3. There really is no excuse for it. If you are in a margin account, regulations permit the trading of unsettled funds without affecting margin requirements, so your funds in effect are available immediately after trading but aren't considered margin loans. Some strict brokers will even restrict the amount of uncleared margin funds you can trade with (Scottrade used to be hyper safe and was the only online discount broker that did this years ago); others will allow you to withdraw a large percentage of your funds immediately (I think E*Trade lets you withdraw up to 90% of unsettled funds immediately). If you are in a cash account, you are authorized to buy with unsettled funds, but you can't sell purchases made on unsettled funds until such funds clear, or you'll be barred for 90 days from trading as your letter threatened; besides, most brokers don't allow this. You certainly aren't allowed to withdraw unsettled funds (by your broker) in such an account as it would technically constitute a loan for which you aren't even liable since you've agreed to no loan contract, a margin agreement. I can't be sure if that actually violates Reg T, but when I am, I'll edit. While it is true that all marketable options are cleared through one central entity, the Options Clearing Corporation, with stocks, clearing & settling still occurs between brokers, netting their transactions between each other electronically. All financial products could clear & settle immediately imo, and I'd rather not start a firestorm by giving my opinion why not. Don't even get me started on the bond market... As to the actual process, it's called \"\"clearing & settling\"\". The general process (which can generally be applied to all financial instruments from cash deposits to derivatives trading) is: The reason why all of the old financial companies were grouped on Wall St. is because they'd have runners physically carting all of the certificates from building to building. Then, they discovered netting so slowed down the process to balance the accounts and only cart the net amounts of certificates they owed each other. This is how we get the term \"\"bankers hours\"\" where financial firms would close to the public early to account for the days trading. While this is all really done instantly behind your back at your broker, they've conveniently kept the short hours.\"", "title": "" }, { "docid": "180148", "text": "\"There are a couple of different things that could be referenced by \"\"cheap money\"\": The money supply itself - This is the Federal Reserve printing more money which could devalue the existing US dollars and thus make the dollars even cheaper since there would be more of them. Interest rates - Currently in the US interest rates are rather low which means that borrowers could possibly get good rates on that money thus making it relatively cheap. Compare current interest rates to the early 1980s and there is a major difference. In terms of implications on the stock market, there are a couple that come to my mind: Investment options - With low interest rates, cash and bonds aren't necessarily yielding that much and thus some people may be more likely to invest elsewhere with stocks being an option. Thus, there may be some people that would rather invest in stocks than hold their investments in lower-yielding options. Corporate spending - If rates stay low, then for companies with good financial track records, they could borrow money to expand operations rather than sell more stock and thus there may be companies that borrow to grow so that they take advantage of these interest rates.\"", "title": "" }, { "docid": "71614", "text": "\">As a legal matter, shareholders who purchase shares of stock in a corporation own nothing more than that—shares of stock. Similarly, bondholders own only bonds, and executives with employment contracts own their contracts. None of these types of ownership give shareholders, bondholders or executives the right to control the firm. The right to control the firm’s assets and actions rests in the hands of its board of directors, and only when they act as a body and follow proper board procedures. All this says is \"\"decisions are made by the board.\"\" This is not news, and it doesn't mean that shareholders do not own the company. Shareholders elect the board, by the way. >An important consequence of this governance structure is that shareholders not only have no legal right to control the firm, they also have no legal right to help themselves to the corporation’s assets. Well, that's wrong. >In fact, the only time shareholders receive any funds directly from the corporation’s coffers is when they receive a dividend or the corporation repurchases their shares. Or, you know, in the case of bankruptcy. >This only happens when the directors vote to declare a dividend or a corporate repurchase. The same directors who were appointed by shareholders. >At law, a principal has a right to control her agent. But shareholders can’t exercise direct control over corporate directors. I suppose this is true in the sense that shareholders cannot practice slavery. But shareholders can, again, vote on issues relating to the governance of the company. >It is thus wildly misleading to describe shareholders as the sole residual claimants in companies that aren’t actually in bankruptcy. This is only true if you're retarded and don't know what \"\"residual\"\" means. >This idea is supported by modern options theory. In effect, bondholders own the right to access cash flow but have sold a call to shareholders, while shareholders own the right to access the cash flow but have sold a put to bondholders. Neither shareholders nor bondholders can claim an exclusive right to “own” the company’s cash flow, much less the company. This is a made up explanation that doesn't mean anything. The real options model of corporate assets is that corporate debt is a risk-free bond with a short put option and equity is a call option. There is no \"\"deal,\"\" in actuality or in spirit, between debt and equity owners. You can dismiss the article as \"\"shit.\"\"\"", "title": "" }, { "docid": "11721", "text": "Whenever you want to spend the weekend with your family, then you can come here to make the special evening in West Palm Beach Escape Rooms. It is a full secure place for the girl, we have good corporate team building escape rooms WPB. We are working together and using your time wisely will you find the clues. We serve you better service all of those escape room, our services are less than expected. The escape rooms are amazing design for those people who want to spend the time with fun and get participate in our activities.", "title": "" }, { "docid": "265965", "text": "Great. But the policies aren’t targeted at him. The government isn’t conspiring to build monopolies. But corporations are definitely conspiring to take advantage of government policies. How about we force corporations to give back to the country relative to what they get from it? Or is the idea of responsible corporations just too much to handle?", "title": "" }, { "docid": "96563", "text": "\"Today sure, but that market is similar to day trading in it's volatility. It's great for individuals to make some money in the short term but it's not a good product to build a company around. Especially since the corporate giants already own the entire marketplace. And you need to take seriously that they have a 50/50 success/fail rate. Facebook is succeeding, Twitter is failing. That's not an indication of stability. Anyway you need to understand the technology and the consumer marketplace to really know what you're talking about and I suspect you don't. No offense intended. I've been using the internet since before computers were \"\"cool\"\" and I do know what I'm talking about.\"", "title": "" }, { "docid": "411375", "text": "\"Because the returns are not good. One of the big drivers in Australia is \"\"negative gearing\"\": if your investment loses money you can offset losses against your tax on other income. Institutional investors and corporations are in the business of making money: not losing it. Housing market investors are betting that these year to year revenue losses will ultimately be made up in a big capital gain: for which individuals get a huge tax break that is also not available to corporations. Capital gains are not guaranteed. Australia has benefited from 25+ years of economic, employment and wages growth: a result of good government planning, strong corporate governance and a fair slice of luck. If this were to end housing prices would plateau at best and crash at worst. A person who has negative cash flow investments has to sell them urgently if they lose their job. A glut of mortgagee sales and property prices could easily come off 20-30%. Rental yields on residential property in Sydney are about 4% with a capital gain of currently 10% but this has been flat or negative within the last 5 years and no doubt will be again within the next 5. Rental yields for residential property are constrained by mortgage rates: if it significantly cheaper to buy then to rent, why would anyone rent? In contrast, industrial and commercial property gets a yield of about 7% and gets exactly the same capital gain. This is because land is land and if the price of industrial land doesn't grow at the same rate as the residential land next door eventually one will be converted into the other. Retail rentals are even higher. In addition commercial tenants are responsible for more outgoings and have fewer legal rights than residential tenants. Further, individual residential properties are horribly illiquid and have large transaction costs. While it is possible to bundle them up into property trusts so that units can be sold on the stock exchange it is far more common to do this with office and retail buildings. This is what companies like Westfield and AMP Capital do. Notwithstanding, heavily geared property trusts can get into deep water because of the illiquid nature of property as the failure of Centro illustrates. That said, there are plenty of companies that develop residential houses and units for sale to owner occupiers or investors because that's where the money is.\"", "title": "" }, { "docid": "110674", "text": "Reversing your math, I am assuming you have $312K to work with. In that case, I would simply shop around your local banks and/or credit unions and have them compete for your money and you might be quite surprised how much they are willing to pay. A couple of months ago, you would be able to get about 4.25% from Israel Bonds in Canada on 5 years term (the Jubilee product, with minimum investment of $25K). It's a bit lower now, but you should still be able to get very good rates if you shop around tier-2 banks or credit unions (who are more hungry for capital than the well-funded tier-1 banks). Or you could look at preferred shares of a large corporation. They are different from common shares in the sense they are priced according to the payout rate (i.e. people buy it for the dividend). A quick screen from your favorite stock exchange ought to find you a few options. Another option is commercial bonds. You should be able to get that kind of return from investment grade (BBB- and higher) bonds on large corporations these days. I just did a quick glance at MarketWatch's Bond section (http://cxa.marketwatch.com/finra/BondCenter/Default.aspx) and found AAA grade bonds that will yield > 5%. You will need to investigate their underlying fundamentals, coupon rate and etc before investing (second thought, grab a introduction to bonds book from Chapters first). Hope these helps.", "title": "" }, { "docid": "30959", "text": "\"Disclosure: I don't have an iPhone, so I don't use RobinHood. That being said, I have a less \"\"they're-out-to-get-ya\"\" view of what they're doing. As a small business owner (2 businesses), employees cost the most. If you can create a solid business with few (or no) employees and let robots run it, you will drastically reduce your costs. Joe Polish said it similarly with sales letters, something along the lines of they never complain about a headache, need to take a year off to discover themself, or just need a personal day. Robots are the same; they do not have human limits. Most simple trading can be done and maintained by well written code and AI, there's very little need for humans to do anything other than build it. Think about the efficiency of bitcoin versus all the central banks combined; how many people are employed by central banks? Robinhood states that they are using technology in these ways to minimize costs and they're using a system that doesn't need physical branches (this doesn't mean they will never have them, just that they don't need them). Robinhood does not indicate that they allow everything to happen for free; only stock trading. I worked for a large trading firm once and observed that stock trading wasn't the bulk of where they made their money anyway; trading options, futures, index funds, etc are where the big money was and Robinhood says nothing about those being free. Like the CQM mentioned too, they'll be charging for margin as well. In a way, the individual stock trader is dead; many people - including this forum - prefer index funds, so more than likely, Robinhood will strike up a deal with an index fund company or create their own (this is just easy, passive income with an expense ratio). In this category, the markets are their playground, but they do need to attract enough people to their platform, thus free stock trading is a good way to do it. As for selling your information for advertising, that is always a possibility, but they have quite a few other options that would be good for most investors (index funds, affiliating with financial fund companies, etc) where they can start before ever needing to dip their toe in selling information. This isn't to say they won't do it, but that there are few other options they have. The major concern I have for Robinhood is ongoing security. Just building it and letting it run kind of assumes that there won't be major compromises in the future and as AI evolves, superior AI might be able to crush older AI.\"", "title": "" }, { "docid": "457805", "text": "Delaware llc incorporation When someone want to do some business, but the person want to have some extremely flexible business so that he can able to start up with low cost and with affordable franchise text they Delaware llc incorporation is a very good choice for doing so. It mainly help to customize the corporation and can also help to choose that option which user want to have.", "title": "" }, { "docid": "257168", "text": "\"A tax return is a document you sign and file with the government to self-report your tax obligations. A tax refund is the payment you receive from the government if your payments into the tax system exceeded your obligations. As others have mentioned, if an extra $2K in income generated $5K in taxes, chances are your return was prepared incorrectly. The selection of an appropriate entity type for your business depends a lot on what you expect to see over the next several years in terms of income and expenses, and the extent to which you want or need to pay for fringe benefits or make pretax retirement contributions from your business income. There are four basic flavors of entity which are available to you: Sole proprietorship. This is the simplest option in terms of tax reporting and paperwork required for ongoing operations. Your net (gross minus expenses) income is added to your wage income and you'll pay tax on the total. If your wage income is less than approximately $100K, you'll also owe self-employment tax of approximately 15% in addition to income tax on your business income. If your business runs at a loss, you can deduct the loss from your other income in calculating your taxable income, though you won't be able to run at a loss indefinitely. You are liable for all of the debts and obligations of the business to the extent of all of your personal assets. Partnership. You will need at least two participants (humans or entities) to form a partnership. Individual items of income and expense are identified on a partnership tax return, and each partner's proportionate share is then reported on the individual partners' tax returns. General partners (who actively participate in the business) also must pay self-employment tax on their earnings below approximately $100K. Each general partner is responsible for all of the debts and obligations of the business to the extent of their personal assets. A general partnership can be created informally or with an oral agreement although that's not a good idea. Corporation. Business entities can be taxed as \"\"S\"\" or \"\"C\"\" corporations. Either way, the corporation is created by filing articles of incorporation with a state government (doesn't have to be the state where you live) and corporations are typically required to file yearly entity statements with the state where they were formed as well as all states where they do business. Shareholders are only liable for the debts and obligations of the corporation to the extent of their investment in the corporation. An \"\"S\"\" corporation files an information-only return similar to a partnership which reports items of income and expense, but those items are actually taken into account on the individual tax returns of the shareholders. If an \"\"S\"\" corporation runs at a loss, the losses are deductible against the shareholders' other income. A \"\"C\"\" corporation files a tax return more similar to an individual's. A C corporation calculates and pays its own tax at the corporate level. Payments from the C corporation to individuals are typically taxable as wages (from a tax point of view, it's the same as having a second job) or as dividends, depending on how and why the payments are made. (If they're in exchange for effort and work, they're probably wages - if they're payments of business profits to the business owners, they're probably dividends.) If a C corporation runs at a loss, the loss is not deductible against the shareholders' other income. Fringe benefits such as health insurance for business owners are not deductible as business expenses on the business returns for S corps, partnerships, or sole proprietorships. C corporations can deduct expenses for providing fringe benefits. LLCs don't have a predefined tax treatment - the members or managers of the LLC choose, when the LLC is formed, if they would like to be taxed as a partnership, an S corporation, or as a C corporation. If an LLC is owned by a single person, it can be considered a \"\"disregarded entity\"\" and treated for tax purposes as a sole proprietorship. This option is not available if the LLC has multiple owners. The asset protection provided by the use of an entity depends quite a bit on the source of the claim. If a creditor/plaintiff has a claim based on a contract signed on behalf of the entity, then they likely will not be able to \"\"pierce the veil\"\" and collect the entity's debts from the individual owners. On the other hand, if a creditor/plaintiff has a claim based on negligence or another tort-like action (such as sexual harassment), then it's very likely that the individual(s) involved will also be sued as individuals, which takes away a lot of the effectiveness of the purported asset protection. The entity-based asset protection is also often unavailable even for contract claims because sophisticated creditors (like banks and landlords) will often insist the the business owners sign a personal guarantee putting their own assets at risk in the event that the business fails to honor its obligations. There's no particular type of entity which will allow you to entirely avoid tax. Most tax planning revolves around characterizing income and expense items in the most favorable ways possible, or around controlling the timing of the appearance of those items on the tax return.\"", "title": "" }, { "docid": "444511", "text": "Most banks offer a college card that has low limits so you can start building credit. Another good option is to get a rewards credit card and do your everyday spending on it, then immediately turn around and pay it. I have seen people that just overpay their credit card just to use it like a debit card, all while earning credit and getting rewarded for it. I work for a bank so I see this alot.", "title": "" } ]
10657	Is the concept of an “odd lot” adjusted to stock price?	[ { "docid": "492503", "text": "I will assume that you are not asking in the context of high frequency trading, as this is Personal Finance Stack Exchange. It is completely acceptable to trade odd lots for retail brokerage customers. The odd lot description that you provided in your link, from Interactive Brokers is correct. But even in that context, it says, regarding the acceptability of odd lots to stock exchanges: The exception is that odd lots can be routed to NYSE/ARCA/AMEX, but only as part of a basket order or as a market-on-close (MOC) order. Google GOOG is traded on the NASDAQ. Everything on the NASDAQ is electronic, and always has been. You will have no problem selling or buying less than 100 shares of Google. There is also an issue of higher commissions with odd lots: While trading commissions for odd lots may still be higher than for standard lots on a percentage basis, the popularity of online trading platforms and the consequent plunge in brokerage commissions means that it is no longer as difficult or expensive for investors to dispose of odd lots as it used to be in the past. Notice what it says about online trading making it easier, not more difficult, to trade odd lots.", "title": "" } ]	[ { "docid": "313421", "text": "\"The Dow Jones Industrial Average (DJIA) is a Price-weighted index. That means that the index is calculated by adding up the prices of the constituent stocks and dividing by a constant, the \"\"Dow divisor\"\". (The value of the Dow divisor is adjusted from time to time to maintain continuity when there are splits or changes in the roster.) This has the curious effect of giving a member of the index influence proportional to its share price. That is, if a stock costing $100 per share goes up by 1%, that will change the index by 10 times as much as if a stock costing $10 per share goes up by the same 1%. Now look at the price of Google. It's currently trading at just a whisker under $700 per share. Most of the other stocks in the index trade somewhere between $30 and $150, so if Google were included in the index it would contribute between 5 and 20 times the weight of any other stock in the index. That means that relatively small blips in Google's price would completely dominate the index on any given day. Until June of 2014, Apple was in the same boat, with its stock trading at about $700 per share. At that time, Apple split its stock 7:1, and after that its stock price was a little under $100 per share. So, post-split Apple might be a candidate to be included in the Dow the next time they change up the components of the index. Since the Dow is fixed at 30 stocks, and since they try to keep a balance between different sectors, this probably wouldn't happen until they drop another technology company from the lineup for some reason. (Correction: Apple is in the DJIA and has been for a little over a year now. Mea culpa.) The Dow's price-weighting is unusual as stock indices go. Most indices are weighted by market capitalization. That means the influence of a single company is proportional to its total value. This causes large companies like Apple to have a lot of influence on those indices, but since market capitalization isn't as arbitrary as stock price, most people see that as ok. Also, notice that I said \"\"company\"\" and not \"\"stock\"\". When a company has multiple classes of share (as Google does), market-cap-weighted indices include all of the share classes, while the Dow has no provision for such situations, which is another, albeit less important, reason why Google isn't in the Dow. (Keep this in mind the next time someone offers you a bar bet on how many stocks are in the S&P 500. The answer is (currently) 505!) Finally, you might be wondering why the Dow uses such an odd weighting in its calculations. The answer is that the Dow averages go back to 1896, when Charles Dow used to calculate the averages by hand. If your only tools are a pencil and paper, then a price-weighted index with only 30 stocks in it is a lot easier to calculate than a market-cap-weighted index with hundreds of constituents. About the Dow Jones Averages. Dow constituents and prices Apple's stock price chart. The split in 2014 is marked. (Note that prices before the split are retroactively adjusted to show a continuous curve.)\"", "title": "" }, { "docid": "111266", "text": "When economies are strong, it is particularly alluring to have a single currency as it makes trade and tourism simpler and helps reduce costs. The problem comes when individual member economies get into trouble. Because the Eurozone is a loose grouping of nations, there is no direct equivalent of the US Federal government to coordinate a response, there is instead an odd mixture of National and Central government that makes it harder to get a unified approach to the economy (OK, it's maybe not so different to the US in reality). This lack of flexibility means that some of the key levers of international finance are compromised, for example a weak economy can't float its currency to improve exports. Similarly individual country's interest rates can't be adjusted to balance spending. I suspect the main reason though is political and based on concepts of sovereignty and national pride. The UK does the majority of its trade with the Eurozone, so the pros would possibly outweigh the cons, but the UK as a whole (and some of our papers in particular) have always regarded Europe with suspicion. Most Brits only speak English and find France and Germany a strange and obtuse place. The (almost) common language makes it easier to relate to the US and Canada than our near neighbours. It seems the perception amongst the political establishment is that any attempt to join the Euro is political suicide, while that is the case it is unlikely to happen. Purely from a personal perspective, I'd welcome the Euro except it means a lot of the products I routinely buy would become a lot more expensive if price is 'harmonised'. For an example compare the price of the iPod Touch in the UK (£209.99) to France(€299). The French pay £262 at the current exchange rate, which is close to 25% more. Ouch. See also my question about Canada adopting the US Dollar", "title": "" }, { "docid": "570787", "text": "Basically, diversifying narrows the spread of possible results, raising the center of the returns bell-curve by reducing the likelihood of extreme results at either the high or low end. It's largely a matter of basic statistics. Bet double-or-nothing on a single coin flip, and those are the only possible results, and your odds of a disaster (losing most or all of the money) are 50%. Bet half of it on each of two coin flips, and your odds of losing are reduced to 25% at the cost of reducing your odds of winning to 25%, with 50% odds that you retain your money and can try the game again. Three coins divides the space further; the extremes are reduced to 12.5% each, with the middle being most likely. If that was all there was, this would be a zero-sum game and pure gambling. But the stock market is actually positive-sum, since companies are delivering part of their profits to their stockholder owners. This moves the center of the bell curve up a bit from break-even, historically to about +8%. This is why index funds produce a profit with very little active decision; they treat the variation as mostly random (which seems to work statistically) and just try to capture average results of a (hopefully) slightly above-average bucket of stocks and/or bonds. This approach is boring. It will never double your money overnight. On the other hand, it will never wipe you out overnight. If you have patience and are willing to let compound interest work for you, and trust that most market swings regress to the mean in the long run, it quietly builds your savings while not driving you crazy worrying about it. If all you are looking for is better return than the banks, and you have a reasonable amount of time before you need to pull the funds out, it's one of the more reliably predictable risk/reward trade-off points. You may want to refine this by biasing the mix of what you're holding. The simplest adjustment is how much you keep in each of several major investment categories. Large cap stocks, small cap stocks, bonds, and real estate (in the form of REITs) each have different baseline risk/return curves, and move in different ways in response to news, so maintaining a selected ratio between these buckets and adding the resulting curves together is one simple way to make fairly predictable adjustments to the width (and centerline) of the total bell curve. If you think you can do better than this, go for it. But index funds have been outperforming professionally managed funds (after the management fees are accounted for), and unless you are interested in spending a lot of time researching and playing with your money the odds of your doing much better aren't great unless you're willing to risk doing much worse. For me, boring is good. I want my savings to work for me rather than the other way around, and I don't consider the market at all interesting as a game. Others will feel differently.", "title": "" }, { "docid": "211543", "text": "Your broker should make you whole by adjusting the quantity of the underlying (see: http://www.schaeffersresearch.com/education/options-basics/key-option-concepts/dividends-stock-splits-and-other-option-contract-adjustments) but I would check with them that this will happen. You will then have an option on 4 times the underlying for each option. Unless the price has risen in the interim or you bought them after the split was announced you should not make a loss.", "title": "" }, { "docid": "349668", "text": "This is more than likely a thing about your financial institution and the exchanges where they trade shares. Some exchanges cannot/will not handle odd lot transactions. Most established brokerages have software and accounting systems that will deal in round lots with the exchanges, but can track your shares individually. Sometimes specific stocks cannot be purchased in odd lots due to circumstances specific to that stock (trading only on a specific exchange, for example). Most brokerages offer dollar-cost averaging programs, but may limit which stocks are eligible, due to odd lot and partial share purchases. Check with your brokerage to see if they can support odd lot and/or DCA purchases. You may find another similar ETF with similar holdings that has better trading conditions, or might consider an open-end mutual fund with similar objectives. Mutual funds allow partial share purchases (you have $100 to invest today, and they issue you 35.2 shares, for example).", "title": "" }, { "docid": "24191", "text": "This is how I've understood this concept. Fibonacci nos/levels/ratios/%s is based on concept of sequential increment. You may find lot of info about Fibonacci on net. In stock market this concept is used to predict psychological level. While a trend is form, usually price tend to accumulate/consolidate at these level. How the percentage/ ratio make impact is - check any long trend...Now draw a fibbo retracement from immediate previous high and connect it's low. You will see new levels of intermediate trend. In broader term you will find after reversal a leg (trend) is formed, then body and then head which is smaller; then price reverses. The first leg that forms if it refuses to break 23.6% or 38.2% then the previous trend may continue. 50% is normal; usually this level is indecision phase. Even 61.8% is seen as indecision but it is crucial level as it is breakout level towards 100%. Now if the stock retraces 100% then it is sign a new big trend is forming. Now for day trader 23.6%,38.2% and 50% level are very crucial from trading purpose. This concept is so realistic that every level is considered and respected. Suppose if a candle or bar starts at 23.6% level and crosses 38.2% and directly hits 50%. Then the next bar or candle will revert and first hit 38.2% and then continue with the trend. It means price comes back, forms it area at this level and then continue whichever direction the force directs it. You never trade fibo alone, you need help of oscillators or other tools to confirm it.", "title": "" }, { "docid": "156923", "text": "A rough estimate of the money you'd need to take a position in a single stock would be: In the case of your Walmart example, the current share price is 76.39, so assuming your commission is $7, and you'd like to buy, say, 3 shares, then it would cost approximately (76.39 * 3) + 7 = $236.17. Remember that the quoted price usually refers to 100-share lots, and your broker may charge you a higher commission or other fees to purchase an odd lot (less than 100 shares, usually). I say that the equation above gives an approximate minimum because However, I second the comments of others that if you're looking to invest a small amount in the stock market, a low cost mutual fund or ETF, specifically an index fund, is a safer and potentially cheaper option than purchasing individual stocks.", "title": "" }, { "docid": "214798", "text": "Like @littleadv, I don't consider a mortgage on a primary residence to be a low-risk investment. It is an asset, but one that can be rather illiquid, depending on the nature of the real estate market in your area. There are enough additional costs associated with home-ownership (down-payment, insurance, repairs) relative to more traditional investments to argue against a primary residence being an investment. Your question didn't indicate when and where you bought your home, the type of home (single-family, townhouse, or condo) the nature of your mortgage (fixed-rate or adjustable rate), or your interest rate, but since you're in your mid-20s, I'm guessing you bought after the crash. If that's the case, your odds of making a profit if/when you sell your home are higher than they would be if you bought in the 2006/2007 time-frame. This is no guarantee of course. Given the amount of housing stock still available, housing prices could still fall further. While it is possible to lose money in all sorts of investments, the illiquid nature of real estate makes it a lot more difficult to limit your losses by selling. If preserving principal is your objective, money market funds and treasury inflation protected securities are better choices than your home. The diversification your financial advisor is suggesting is a way to manage risk. Not all investments perform the same way in a given economic climate. When stocks increase in value, bonds tend to decrease (and vice versa). Too much money in a single investment means you could be wiped out in a downturn.", "title": "" }, { "docid": "555226", "text": "\"I've alway thought that it was strange, but the \"\"price\"\" that gets quoted on a stock exchange is just the price of the last transaction. The irony of this definition of price is that there may not actually be any more shares available on the market at that price. It's also strange to me that the price isn't adjusted at all for the size of the transaction. A transaction of just 1 share will post a new price even if just seconds earlier 100,000 shares traded for a different price. (Ok, unrealistic example, but you get my point.) I've always believed this is an odd way to describe the price. Anyway, my diatribe here is supposed to illustrate the point that the fluctuations you see in price don't really reflect changing valuations by the stock-owning public. Each post in the exchange maintains a book of orders, with unmatched buy orders on one side and unmatched sell orders on the other side. If you go to your broker and tell him, \"\"fill my order for 50,000 shares at market price\"\", then the broker won't fill you 50,000 shares at .20. Instead, he'll buy the 50 @ .22, then 80 @ .23, then 100 @ .30, etc. Because your order is so large compared to the unmatched orders, your market order will get matched a bunch of the unmatched orders on the sell side, and each match will notch the posted price up a bit. If instead you asked the broker, \"\"open a limit order to buy 50000 shares at .20\"\", then the exchange will add your order to the book: In this case, your order likely won't get filled at all, since nobody at the moment wants to sell at .20 and historically speaking it's unlikely that such a seller will suddenly appear. Filling large orders is actually a common problem for institutional investors: http://www.businessweek.com/magazine/content/05_16/b3929113_mz020.htm http://www.cis.upenn.edu/~mkearns/papers/vwap.pdf (Written by a professor I had in school!)\"", "title": "" }, { "docid": "350748", "text": "\"This is because volatility is cumulative and with less time there is less cumulative volatility. The time value and option value are tied to the value of the underlying. The value of the underlying (stock) is quite influenced by volatility, the possible price movement in a given span of time. Thirty days of volatility has a much broader spread of values than two days, since each day benefits from the possible price change of the prior days. So if a stock could move up to +/- 1% in a day, then compounded after 5 days it could be +5%, +0%, or -5%. In other words, this is compounded volatility. Less time means far less volatility, which is geometric and not linear. Less volatility lowers the value of the underlying. See Black-Scholes for more technical discussion of this concept. A shorter timeframe until option expiration means there are fewer days of compounded volatility. So the expected change in the underlying will decrease geometrically. The odds are good that the price at T-5 days will be close to the price at T-0, much more so than the prices at T-30 or T-90. Additionally, the time value of an American option is the implicit put value (or implicit call). While an \"\"American\"\" option lets you exercise prior to expiry (unlike a \"\"European\"\" option, exercised only at expiry), there's an implicit put option in a call (or an implicit call in a put option). If you have an American call option of 60 days and it goes into the money at 30 days, you could exercise early. By contract, that stock is yours if you pay for it (or, in a put, you can sell whenever you decide). In some cases, this may make sense (if you want an immediate payoff or you expect this is the best price situation), but you may prefer to watch the price. If the price moves further, your gain when you use the call may be even better. If the price goes back out of the money, then you benefited from an implicit put. It's as though you exercised the option when it went in the money, then sold the stock and got back your cash when the stock went out of the money, even though no actual transaction took place and this is all just implicit. So the time value of an American option includes the implicit option to not use it early. The value of the implicit option also decreases in a nonlinear fashion, since the value of the implicit option is subject to the same valuation principles. But the larger principle for both is the compounded volatility, which drops geometrically.\"", "title": "" }, { "docid": "260384", "text": "\"Yes, you can insure against the fall in price of stock by purchasing a put option. You pay for a put and if the price of the share falls below the \"\"strike price\"\" of the put, then you can exercise the put. On exercise, the person who sold you the put contract agrees to buy the stock for the strike price, even though that strike price is higher than the market price. You can adjust the level of insurance by buying put options at higher or lower prices, or buying fewer put options than shares you own (leaving some shares uninsured). Alternatively, you can minimize your risk exposure by investing in an index or other fund, which gives you partial ownership in a large number of shares. That means on any given day, lots of shares do worse and lots of shares do better. You can reduce the need for insurance by purchasing a lower-risk, lower-growth financial product.\"", "title": "" }, { "docid": "325393", "text": "It looks more like someone is trying to pocket the spread. The trades are going off at the bid then the ask (from what I can tell without any L1 and L2 data, but the spread could be bigger than what the prices show, since the stock looks pretty volatile given the difference between current price and VWAP...). Looking through the JSE rule books I didn't find any special provisions on how they handle odd lots in their Central Order Book, but the usual practice in other markets is to display only round lot orders. So these 4 share orders would remain hidden from book participants and could be set there to trigger executions from those who are probing for limit orders. Or to make a market with very limited risk.", "title": "" }, { "docid": "25080", "text": "When volatility is higher, the option is more likely to end up in-the-money. Moreover, when it ends up in-the-money, it is likely to be over the strike price by a greater amount. Consider a call option. With high volatility, moves in the stock price are big - both up moves and down moves. If the stock moves up by a lot, the call option holder will benefit greatly. On the other hand, when the stock moves down, below a certain point the option holder does not care how big a down move the stock has. His downside is limited. Hence, the value of the option is increased by high volatility. I know everyone who searches this is looking for this answer. Bump so people are able to get this concept instead of looking all over the web for it.", "title": "" }, { "docid": "380351", "text": "Specific stock advice isn't permitted on these boards. I'm discussing the process of a call spread with the Apple Jan 13 calls as an example. In effect, you have $10 to 'bet.' Each bet you'd construct offers a different return (odds). For example, If you bought the $750 call at $37.25, you'd need to look to find what strike has a bid of $27 or higher. The $790 is bid $27.75. So this particular spread is a 4 to 1 bet the stock will close in January over $790, with a $760 break even. You can pull the number from Yahoo to a spreadsheet to make your own chart of spread costs, but I'll give one more example. You think it will go over $850, and that strike is now ask $18.85. The highest strike currently listed is $930, and it's bid $10.35. So this spread cost is $850, and a close over $930 returns $8000 or over 9 to 1. Again, this is not advice, just an analysis of how spreads work. Note, any anomalies in the pricing above is the effect of a particular strike having no trades today, not every strike is active so 'last trade' can be days old. Note: My answer adds to AlexR's response in that once you used the word bet and showed a desire to make a risky move, options are the answer. You acknowledged you understand the basic concept, but given the contract size of 100 shares, these suggestions are ways to bet under your $1000 limit and profit from the gain in the underlying stock you hope to see.", "title": "" }, { "docid": "509795", "text": "Auto-correlation is a statistical concept for measuring repeating patterns in series. In stocks it is of particular interest as if future prices can be reliably guessed from past prices a lot of money could be made. Note, even in cases where auto-correlations are high and persistent (near 1) there is still some possibility that the next time period would be down even if the previous period was up. Now the important part here is that high and persistent auto-correlation also means once the price falls the next period the price is also more likely to fall! Once one period was down the next period is more likely to be down so the price does not need to go to infinity. Instead, it generally would display up and down trends. Now, the key word above for investing is persistence. For stocks, auto-correlations are, at best, weakly persistent at reasonable time scales. So, even if a stock was highly auto-correlated during a previous period it is tough to make consistent money off of trading on these past trending patterns. This does not mean some people don't try...", "title": "" }, { "docid": "468144", "text": "Even without fraud, a company can get into serious trouble overnight, often through no fault of their own. That's part of the hazard of being part owner of a company -- which is what a share of stock is. As a minority owner not involved in actually running the business, there really isn't a lot you can do about that excep to play the odds and think about how that risk compares to the profit you're taking (which is one reason the current emphasis on stock price rather than dividends is considered a departure from traditional investing) and, as everyone else has said, avoid putting too much of your wealth in one place.", "title": "" }, { "docid": "179649", "text": "If you want to monitor how well you did in choosing your investments you will want to use stock prices that account for the dividends and splits and other changes (not just the closing price). The adjusted close will include these changes where the straight close will not include them. Using the adjusted close you will get your true percentage change. For example I have a stock called PETS that paid an $0.18 dividend in July 2015. The adjusted closes before that day in July are all $0.18 lower per share. Say the closing price had been unchanged at $20.00. The close prices would say I made no profit, but the adjusted closing price would say I made $0.18 per share on this investment because the adjusted close would read $19.82 in June 2015 but would read $20.00 in August 2015 (just like the closing price). The adjusted close allows me to know my true profit per share.", "title": "" }, { "docid": "529996", "text": "This is a great question for understanding how futures work, first let's start with your assumptions The most interesting thing here is that neither of these things really matters for the price of the futures. This may seem odd as a futures contract sounds like you are betting on the future price of the index, but remember that the current price already includes the expectations of future earnings as well! There is actually a fairly simple formula for the price of a futures contract (note the link is for forward contracts which are very similar but slightly more simple to understand). Note, that if you are given the current price of the underlying the futures price depends essentially only on the interest rate and the dividends paid during the length of the futures contract. In this case the dividend rate for the S&P500 is higher than the prevailing interest rate so the futures price is lower than the current price. It is slightly more complicated than this as you can see from the formula, but that is essentially how it works. Note, this is why people use futures contracts to mimic other exposures. As the price of the future moves (pretty much) in lockstep with the underlying and sometimes using futures to hedge exposures can be cheaper than buying etfs or using swaps. Edit: Example of the effect of dividends on futures prices For simplicity, let's imagine we are looking at a futures position on a stock that has only one dividend (D) in the near term and that this dividend happens to be scheduled for the day before the futures' delivery date. To make it even more simple lets say the price of the stock is fairly constant around a price P and interest rates are near zero. After the dividend, we would expect the price of the stock to be P' ~ P - D as if you buy the stock after the dividend you wouldn't get that dividend but you still expect to get the rest of the value from additional future cash flows of the company. However, if we buy the futures contract we will eventually own the stock but only after the dividend happens. Since we don't get that dividend cash that the owners of the stock will get we certainly wouldn't want to pay as much as we would pay for the stock (P). We should instead pay about P' the (expected) value of owning the stock after that date. So, in the end, we expect the stock price in the future (P') to be the futures' price today (P') and that should make us feel a lot more comfortable about what we our buying. Neither owning the stock or future is really necessarily favorable in the end you are just buying slightly different future expected cash flows and should expect to pay slightly different prices.", "title": "" }, { "docid": "124230", "text": "A general rule of thumb is to avoid having more than 5% of your investments in any single stock, to avoid excessive risk; it's usually even more risky if you're talking company stock because an adverse event could result in an inferior stock price and you getting laid off. Under other circumstances, the ideal amount of company stock is probably 0%. But there are tax benefits to waiting, as you've noted, and if you're reasonably confident that the stock isn't likely to jerk around too much, and you have a high risk tolerance (i.e. lots of extra savings besides this), and you're comfortable shouldering the risk of losing some money, it might make sense to hold onto the stock for a year - but never any longer. The real risk to holding a lot of company stock doesn't depend on how often you buy it and sell it per se, but having period purchases every month should make it easier for you to ladder the funds, and regularly sell your old shares as you purchase new shares. You might also consider a stop-loss order on the stock at or near the price you purchased it at. If the stock is at $100, then you buy at $85, and then the stock drops to $85, there are no more outstanding tax benefits and it makes no sense to have it as part of your portfolio instead of any other speculative instrument - you probably get better diversification benefits with any other speculative instrument, so your risk-adjusted returns would be higher.", "title": "" }, { "docid": "10797", "text": "A CFD is like a bet. Bookies don't own horses or racetracks but you still pay them and they pay you if the horses win. If you buy a CFD the money goes to the firm you bought it from and if the stock price changes in your favour, they will pay you. However, if it goes against you they may ask you for more money than you originally invested to cover your losses. Constacts for difference are derivatives, i.e. you gain on the change in the price or delta of something rather than on its absolute value. Someone bets one way and is matched with someone (or perhaps more than one) betting the other way. Both parties are bound by the contract to pay or be payed on the outcome. One will win and the other will necessarily lose. It's similar in concept to a spread bet, although spread bets often have a fixed timescale whereas CFDs do not and CFDs generally operate via the payment of a commission rather than via charges included in the spread. There's more information on both CFDs and spread betting here If somone has a lot of CFDs that might affect the stock price if it's known about as others may buy/sell real stock to either make the CFD pay or may it not pay depending on whether they think they can make money on it. Otherwise CFDs don't have much of an effect on stock prices.", "title": "" }, { "docid": "191688", "text": "Assuming you were immersed in math with your CS degree, the book 'A Non-Random Walk Down Wall Street' by Andrew Lo is a very interesting book about the random walk hypothesis and it's application to financial markets and how efficient markets might not necessarily imply complete randomness. Lots of higher level concepts in the book but it's an interesting topic if you are trying to branch out into the quant world. The book isn't very specific towards algorithmic trading but it's good for concept and ideas. Especially for general finance, that will give you a good run down about markets and the way we tackle modern finance. A Random Walk Down Wall Street (which the book above is named after) by Burton Malkiel is also supposed to be a good read and many have suggested reading it before the one I listed above, but there really isn't a need to do so. For investing specifically, many mention 'The Intelligent Investor' by Benjamin Graham who is the role model for the infamous Warren Buffet. It's an older book and really dry and I think kind of out dated but mostly still relevant. It's more specifically about individual trading rather than markets as a whole or general markets. It sounds like you want to learn more about markets and finance rather than simply trading or buying stocks. So I'd stick to the Andrew Lo book first. --- Also, since you might not know, it would be a good idea to understand the capital asset pricing model, free cash flow models, and maybe some dividend discount models, the last of which isn't so much relevant but good foundations for your finance knowledge. They are models using various financial concepts (TVM is almost used in every case) and utilizing them in various ways to model certain concepts. You'd most likely be immersed in many of these topics by reading a math-oriented Finance book. Try to stay away from those penny stock trading books, I don't think I need to tell a math major (who is probably much smarter than I am) that you don't need to be engaging in penny stocks, but do your DD and come to a conclusion yourself if you'd like. I'm not sure what career path you're trying to go down (personal trading, quant firm analyst, regular analyst, etc etc) but it sounds like you have the credentials to be doing quant trading. --- Check out www.quantopian.com. It's a website with a python engine that has all the necessary libraries installed into the website which means you don't have to go through the trouble yourself (and yes, it is fucking trouble--you need a very outdated OS to run one of the libraries). It has a lot of resources to get into algorithmic trading and you can begin coding immediately. You'd need to learn a little bit of python to get into this but most of it will be using matplotlib, pandas, or some other library and its own personal syntax. Learning about alpha factors and the Pipeline API is also moderately difficult to get down but entirely possible within a short amount of dedicated time. Also, if you want to get into algorithmic trading, check out Sentdex on youtube. He's a python programmer who does a lot of videos on this very topic and has his own tool on quantopian called 'Sentiment Analyzer' (or something like that) which basically quantifies sentiment around any given security using web scrapers to scrape various news and media outlets. Crazy cool stuff being developed over there and if you're good, you can even be partnered with investors at quantopian and share in profits. You can also deploy your algorithms through the website onto various trading platforms such as Robinhood and another broker and run your algorithms yourself. Lots of cool stuff being developed in the finance sector right now. Modern corporate finance and investment knowledge is built on quite old theorems and insights so expect a lot of things to change in today's world. --- With a math degree, finance should be like algebra I back in the day. You just gotta get familiar with all of the different rules and ideas and concepts. There isn't that much difficult math until you begin getting into higher level finance and theory, which mostly deals with statistics anyways like covariance and regression and other statistic-related concepts. Any other math is simple arithmetic.", "title": "" }, { "docid": "571677", "text": "Hey, I'm sure its been asked before and I've read around a bit online, but wondering your guys opinion... You could say I was sort of a late bloomer in terms of maturity/awareness. Well, regardless, I've found myself extremely interested in stocks and options and would love to get a CFA some day (like most other people on this sub). Only problem is, I'm not nearly qualified on paper for a career in finance at this point. I work in a back office support center of one of the largest insurance companies in the world. I began interning there a little over a year ago, made myself familiar with all their products, taught myself tons of concepts etc. I got Bloomberg Certified (not that thats an accomplishment or anything). So I think I have a decent understanding of concepts/valuation. But I don't have any formal modeling experience, though I have played around in Excel a bit. I studied abroad spring semester of last year and interned at a strategic communications firm that worked closely with private companies, which I thoroughly researched along with legislation, policy, etc. I'm wondering what, if any, options I have to transition to a career in finance. I'd assume MBA so far based on my reading, but I'm wondering if anyone thinks I could make a half decent case for say, an entry-level equity research role. I'm based out of the greater New York area though, which probably doesn't help my odds. I know I have a lot left to learn still, but I think I am actually interested for the right reasons - I love the markets. I think I know how to research/analyze decently and could do the job. But I know I'm not a compelling candidate on paper. Any ideas for breaking in? Or should I just sit tight for a few years, get my MBA and try to transition then?", "title": "" }, { "docid": "305983", "text": "According to Active Equity Management by Zhou and Jain: When a stock pays dividend, the adjusted price in Yahoo makes the following adjustment: Let T be the ex-dividend date (the first date that the buyers of a stock will not receive the dividend) and T-1 be the last trading day before T. All prices before T are adjusted by a multiplier (C_{T-1} - d_T)/C_{T-1}, where C_{T-1} is the close price at T-1 and d_T is the dividend per share. This, of course means that the price before T decreases.", "title": "" }, { "docid": "422183", "text": "\"I don't agree that the market as a whole is a ponzi scheme, but there are some ponzi-like aspects to it. If you buy high quality stocks like Coca Cola, Johnson and Johnson, AT&T, Verizon, Kraft, Wells Fargo (the vanilla bank, not one of the crazy ones), IBM, Berkshire Hathaway etc and simply hold onto them for the next 10-20 years, you will make money. Even over the last decade, when stocks \"\"went nowhere\"\", you still came out ahead through the dividend payments. It was just at an unsatisfactory rate of return. Also \"\"the market\"\" consists of a lot more than just stocks. Corporate bonds are a big market and I always recommend people to look at bonds. If you cannot judge whether a company is credit worthy, how can you invest in the common stock? I've made a lot more money myself in the bond market than in the stock market. However, for many stocks, they do look a lot like ponzi schemes. This is true, in particular, with many of the tech stocks (Cuban was a tech investor, so that is probably where his sentiment is coming from). You have many of these companies that create great products. However, they never have positive cash flow because all the money is spent to develop new products. As the share price goes up, the company issues new shares to fund research, stock options to employees to enrich them, etc. However, eventually, they run into a string of bad research that do not yield a new product and the share price plunges. Perhaps the company goes bankrupt. So you have a company that developed great products, but the shareholders never got a penny in dividends and the final shareholders have paper worth zero. Take a look at Research in Motion for example. Creating the Blackberry has to be one of the biggest successes in tech over the last decade. However, has the shareholders gotten any richer? Only if they traded amongst themselves, nobody got a dividend. What happened to the many billions of dollars they made during the peak popularity years of Blackberry? It went to executives, employees, and was squandered on development that did not effectively defend the phone's dominant market position. Now the stock price is back down to the pre-prime years, and if a shareholder held onto it throughout the entire period, he would not have received a single penny. And this is a profitable enterprise, things look even more bizarre when you start looking at the tech companies that have NEVER had a positive earnings quarter and no plans to ever have positive earnings (something like Pandora comes to mind). Often, management at these more bizarre companies run the company as a toy - to play with their own ideas and to issue themselves stock as compensation. And of course, they sell a lot of the stock to cash in before they delve into the next risky venture. They have no intention of ever enriching anybody who holds into the stock in the long run. If for some reason they make money, they will put it all into their next toy project until one of them fails and wipes everything out. If you invest in a profitable business with reasonable management, you will generally come out ahead. Some businesses get displaced by unpredictable circumstances and they go bankrupt. But on average, if a company is good at doing something and they pay out the earnings, you come out ahead. You get in trouble when businesses are good at something, and they take all the money they make and put it into doing something they are not good at. A business might only provide good cashflow for 10-20 years when the product is popular and before competitors cut into margins. If that money is squandered, the long term shareholder may ultimately have very terrible results. The long term shareholder ends up being the guy who keeps going all-in on a 80%-chance-to-win bet (that is what management is doing when they bet the company on the next unproven product), but eventually he gets zeroed out on one loss. This is why if you look at Buffett's investments, they are all in simple businesses that spits off cash to the owner/shareholder. Businesses like soft drinks, snacks, rail roads, vanilla banking, utility-like energy companies, insurance, etc. You might be good at judging the odds of whether a business will succeed or not (aka make more money than your original investment or not). But you don't want management of that company to make a wildly different bet for you. Just because they are great at operating a company doesn't mean they are good enough at judging odds or disciplined enough to make those bets for you. I may have predicted accurately that Business X will be a great success, but if manage takes those profits and goes all in on Business Y, without giving me a chance to cash out, that may have disasterous results.\"", "title": "" }, { "docid": "250018", "text": "\"not sure if I will help or just spread more gibberish but maybe the first concept I'd look at is risk tolerance. Risk tolerance is discerning your ability to risk losing money to get better results. So you know the saying \"\"the higher the risk the higher the reward\"\"? The way most people are going to operate is somewhere on the midpoint of behavior - not doing the riskiest thing, but not doing the very most cautious thing either. So given that concept, some investments will be more appealing given different economic scenarios. Typically stocks are going to reward your investment a little more aggressively than a treasury bond if the economy is humming along. This drives prices of treasuries lower, stock yields higher. In a crappy economy, people want to move their money into conservative investments like a treasury bond. Bond prices rise while stock prices dip. If you google 'correlations between the market prices of stocks and the market prices of Treasury bonds' you will find plenty of helpful and hopefully not too convoluted articles a la http://finance.zacks.com/correlation-treasuries-stocks-10871.html Don't get freaked out by graphs, the graphs are just a way to put into a picture that correlation.\"", "title": "" }, { "docid": "160922", "text": "You might want to consider 'investing' a portion of that money into educating yourself. The payoff might not be as immediately obvious or gratifying but with appropriate determination, in the long term it will generate you a much greater return. If you would like to learn about investing, a great starting point would be to buy and read the book 'The Intelligent Investor' by Benjamin Graham. This will be a great barometer for how ready you are to invest in the stock market. If you are able to understand the concepts discussed and comprehend why they are important, you will have gone far in ensuring that you will make adequate returns over your lifetime and will - more importantly - increase the odds of safeguarding your capital.", "title": "" }, { "docid": "6771", "text": "Conceptually, yes, you need to worry about it. As a practical matter, it's less likely to be exercised until expiry or shortly prior. The way to think about paying a European option is: [Odds of paying out] = [odds that strike is in the money at expiry] Whereas the American option can be thought of as: [Odds of paying out] = [odds that strike price is in the money at expiry] + ( [odds that strike price is in the money prior to expiry] * [odds that other party will exercise early] ). This is just a heuristic, not a formal financial tool. But the point is that you need to consider the odds that it will go into the money early, for how long (maybe over multiple periods), and how likely the counterparty is to exercise early. Important considerations for whether they will exercise early are the strategy of the other side (long, straddle, quick turnaround), the length of time the option is in the money early, and the anticipated future movement. A quick buck strategy might exercise immediately before the stock turns around. But that could leave further gains on the table, so it's usually best to wait unless the expectation is that the stock will quickly reverse its movement. This sort of counter-market strategy is generally unlikely from someone who bought the option at a certain strike, and is equivalent to betting against their original purchase of the option. So most of these people will wait because they expect the possibility of a bigger payoff. A long strategy is usually in no hurry to exercise, and in fact they would prefer to wait until the end to hold the time value of the option (the choice to get out of the option, if it goes back to being unprofitable). So it usually makes little sense for these people to exercise early. The same goes for a straddle, if someone is buying an option for insurance or to economically exit a position. So you're really just concerned that people will exercise early and forgo the time value of the American option. That may include people who really want to close a position, take their money, and move on. In some cases, it may include people who have become overextended or need liquidity, so they close positions. But for the most part, it's less likely to happen until the expiration approaches because it leaves potential value on the table. The time value of an option dwindles at the end because the implicit option becomes less likely, especially if the option is fairly deep in the money (the implicit option is then fairly deep out of the money). So early exercise becomes more meaningful concern as the expiration approaches. Otherwise, it's usually less worrisome but more than a nonzero proposition.", "title": "" }, { "docid": "511355", "text": "Airbnb always knew hotels would eventually fight back. Now they are. That’s why they are offering experiences. When that concept dries up and the people with listings realize guests want a better price they will adjust the price lower. This is short term. I don’t think airbnb have any thing to worry about. The users on Airbnb will win over hotels forcing hotels to close. The hotel market will be less saturated and hotels will eventually slowly but surely die out.", "title": "" }, { "docid": "186869", "text": "A lot may depend on the nature of a buyout, sometimes it's is for stock and cash, sometimes just stock, or in the case of this google deal, all cash. Since that deal was used, we'll discuss what happens in a cash buyout. If the stock price goes high enough before the buyout date to put you in the money, pull the trigger before the settlement date (in some cases, it might be pulled for you, see below). Otherwise, once the buyout occurs you will either be done or may receive adjusted options in the stock of the company that did the buyout (not applicable in a cash buyout). Typically the price will approach but not exceed the buyout price as the time gets close to the buyout date. If the buyout price is above your option strike price, then you have some hope of being in the money at some point before the buyout; just be sure to exercise in time. You need to check the fine print on the option contract itself to see if it had some provision that determines what happens in the event of a buyout. That will tell you what happens with your particular options. For example Joe Taxpayer just amended his answer to include the standard language from CBOE on it's options, which if I read it right means if you have options via them you need to check with your broker to see what if any special exercise settlement procedures are being imposed by CBOE in this case.", "title": "" }, { "docid": "180644", "text": "Your question is a bit odd in that you are mixing long-term fundamental analysis signals which are generally meant to work on longer time frames with medium term trading where these fundamental signals are mostly irrelevant. Generally you would buy-and-hold on a fundamental signal and ride the short-term fluctuations if you believe you have done good analysis. If you would like to trade on the 2-6 month time scale you would need a signal that works on that sort of time scale. Some people believe that technical analysis can give you those kind of signals, but there are many, many, many different technical signals and how you would trade using them is highly dependent on which one you believe works. Some people do mix fundamental and technical signals, but that can be very complicated. Learning a good amount about technical analysis could get you started. I will note, though, that studies of non-professionals continuously show that the more frequently people trade the more on they underperform on average in the long term when compared with people that buy-and-hold. An aside on technical analysis: michael's comment is generally correct though not well explained. Say Bob found a technical signal that works and he believes that a stock that costs $10 dollars should be $11. He buys it and makes money two months later when the rest of the market figures out the right price is $11 and he sells at that price. This works a bunch of times and he now publishes how the signal works on Stack Exchange to show everyone how awesome he is. Next time, Bob's signal finds a different stock at $10 that should be $11, but Anna just wrote a computer program that checks that signal Bob published faster than he ever could. The computer program buys as much as it can in milliseconds until the price is $11. Bob goes to buy, but now it is too late the price is already $11 and he can't make any money. Eventually, people learn to anticipate/adjust for this signal and even Anna's algorithms don't even work anymore and the hunt for new signals starts again.", "title": "" } ]
5adbfa8e55429947ff173887	Which ethnic subgenre included a 1996 action-gangster film set in Gary, indiana?	[ { "docid": "2082449", "text": "Original Gangstas is a 1996 action-gangster film filmed and set in urban Gary, Indiana starring Blaxploitation film stars such as Fred Williamson, Pam Grier, Jim Brown, and Richard Roundtree. The film is directed by Larry Cohen.", "title": "" }, { "docid": "18934784", "text": "Blaxploitation or blacksploitation is an ethnic subgenre of the exploitation film, emerging in the United States during the early 1970s. Blaxploitation films were originally made specifically for an urban black audience, but the genre's audience appeal soon broadened across racial and ethnic lines. The Los Angeles National Association for the Advancement of Colored People (NAACP) head and ex-film publicist Junius Griffin coined the term from the words \"black\" and \"exploitation.\" Blaxploitation films were the first to regularly feature soundtracks of funk and soul music and primarily black casts. \"Variety\" credited \"Sweet Sweetback's Baadasssss Song\" and the less radical Hollywood-financed film \"Shaft\" (both released in 1971) with the invention of the blaxploitation genre.", "title": "" } ]	[ { "docid": "12221", "text": "A film genre is a motion picture category based on similarities in either the narrative elements or the emotional response to the film (namely, serious, comic, etc.). Most theories of film genre are borrowed from literary genre criticism. The basic genres include fiction and documentary, from which subgenres have emerged, such as docufiction and docudrama. Other subgenres include the courtroom and trial-focused drama known as the legal drama. Types of fiction which may seem unrelated can also be combined to form hybrid subgenres, such as the melding of horror and comedy in the \"Evil Dead\" films. Other popular combinations are the romantic comedy and the action comedy film.", "title": "" }, { "docid": "15906930", "text": "Mafia films — a version of gangster films — are a subgenre of crime films dealing with organized crime, often specifically with the Mafia. Especially in early mob films, there is considerable overlap with \"film noir\". Popular regional variations of the genre include Italian \"Poliziotteschi\", Chinese \"Triad films\" and Japanese \"Yakuza films\".", "title": "" }, { "docid": "54369380", "text": "Gangster film is a genre of film that focuses on gangs and organized crime. It is a subgenre of crime film, that may involve large criminal organizations, or small gangs formed to perform a certain illegal act. The genre is differentiated from Westerns and the gangs of that genre.", "title": "" }, { "docid": "5866715", "text": "Mafia comedy films are a subgenre hybrid of comedy films and crime/gangster films.", "title": "" }, { "docid": "55161252", "text": "The Chain is a 1996 American action film directed by Luca Bercovici for Columbia Tristar and starring Gary Busey.", "title": "" }, { "docid": "160750", "text": "Slasher films are a subgenre of horror films, typically involving a violent psychopath stalking and murdering several people, usually with bladed tools. Although the term \"slasher\" is sometimes used informally as a generic term for any horror movie involving murder, analysts of the genre cite an established set of characteristics which set these films apart from other horror subgenres, such as splatter films and psychological horror films.", "title": "" }, { "docid": "682257", "text": "Set It Off is a 1996 American crime action film directed by F. Gary Gray and written by Kate Lanier and Takashi Bufford. The film stars Jada Pinkett Smith, Queen Latifah, Vivica A. Fox and Kimberly Elise (in her film debut). It follows four close friends in Los Angeles, California, who decide to plan and execute a bank robbery. They decide to do so for different reasons, although all four want better for themselves and their families. The film became a critical and box office success, grossing over $41 million against a budget of $9 million.", "title": "" }, { "docid": "5881444", "text": "Kung fu film () is a subgenre of martial arts films and Hong Kong action cinema set in the contemporary period and featuring realistic martial arts. It lacks the fantasy elements seen in \"wuxia\", a related martial arts genre that uses historical settings based on ancient China. Swordplay is also less common in kung-fu films than in \"wuxia\" and fighting is done through unarmed combat.", "title": "" }, { "docid": "14814", "text": "Dr. Henry Walton \"Indiana\" Jones Jr. is a title character and protagonist of the \"Indiana Jones\" franchise. George Lucas created the character in homage to the action heroes of 1930s film serials. The character first appeared in the 1981 film \"Raiders of the Lost Ark\", to be followed by \"Indiana Jones and the Temple of Doom\" in 1984, \"Indiana Jones and the Last Crusade\" in 1989, \"The Young Indiana Jones Chronicles\" from 1992 to 1996, and \"Indiana Jones and the Kingdom of the Crystal Skull\" in 2008. The character is also featured in novels, comics, video games, and other media. Jones is also featured in several Disney theme parks, including the Indiana Jones Adventure, Indiana Jones et le Temple du Péril, and \"Epic Stunt Spectacular!\" attractions.", "title": "" }, { "docid": "39449371", "text": "KL Gangster is a 2011 Malaysian action film written and directed by Syamsul Yusof, (who also starred in the film). The film stars Aaron Aziz, Ady Putra, Soffi Jikan and Zizan Razak. \"KL Gangster\" follows Malek (Aziz) who is a former gangster fresh out of prison, wanting to change his life.", "title": "" }, { "docid": "19179215", "text": "Gary Mooney (1930 – August 5, 2008) was an American animator who worked for Walt Disney Studios, Hubley Studios and fellow animator Jay Ward during his career, which spanned several decades from the 1950s to the 2000s (decade). Some of the most famous projects in which Mooney participated in included Disney's \"Sleeping Beauty\", \"Lady and the Tramp\" and Ward's \"George of the Jungle\". He also worked on several live action films. Mooney also completed many animated sequences, title sequences and graphics for use in live action films, television shows and commercials.", "title": "" }, { "docid": "51888", "text": "Indiana Jones and the Last Crusade is a 1989 American action-adventure film directed by Steven Spielberg, from a story co-written by executive producer George Lucas. It is the third installment in the \"Indiana Jones\" franchise. Harrison Ford reprises the title role and Sean Connery plays Indiana's father, Henry Jones, Sr. Other cast members featured include Alison Doody, Denholm Elliott, Julian Glover, River Phoenix, and John Rhys-Davies. In the film, set largely in 1938, Indiana searches for his father, a Holy Grail scholar, who has been kidnapped by Nazis.", "title": "" }, { "docid": "32041803", "text": "Westside (also spelled West Side) is a neighborhood in west-central Gary, Indiana, USA, bounded by the Cline Avenue expressway on the west, the Norfolk Southern railroad on the north, Clark Road on the east and 25th Avenue on the south. It lies directly east of the Hessville neighborhood of Hammond. Within Gary, it adjoins the neighborhoods of Brunswick, Tolleston and Black Oak. In 2000, Westside had a population of 6,153, which was 63.3% African-American and 31.9% white, with 10.1% Hispanic ethnicity.", "title": "" }, { "docid": "52300193", "text": "Vikram Vedha is a 2017 Indian Tamil-language action film written and directed by Pushkar and Gayathri and produced by Y NOT Studios. The film features R. Madhavan and Vijay Sethupathi in the title roles of an earnest police officer and a notorious don from North Chennai respectively. The cast also includes Varalaxmi Sarathkumar, Shraddha Srinath and Kathir in significant roles. Based on the Indian meta-folktale \"Baital Pachisi\" (\"Vedhala Kadhai\" in Tamil), the film tells the story of a tough police officer who sets out to track down and kill an equally tough gangster.", "title": "" }, { "docid": "417849", "text": "The action game is a video game genre that emphasizes physical challenges, including hand–eye coordination and reaction-time. The genre includes diverse subgenres such as fighting games, shooter games and platform games which are widely considered the most important action games, though multiplayer online battle arena and some real-time strategy games are also considered to be action games.", "title": "" }, { "docid": "19028", "text": "Martial arts film is a film genre. A subgenre of the action film, martial arts films contain numerous martial arts fights between characters. They are usually the films' primary appeal and entertainment value, and often are a method of storytelling and character expression and development. Martial arts are frequently featured in training scenes and other sequences in addition to fights. Martial arts films commonly include other types of action, such as hand-to-hand combats, stuntwork, chases, and gunfights.", "title": "" }, { "docid": "44040964", "text": "Gangster Payday (大茶飯) is a 2014 Hong Kong action comedy drama film directed by Lee Po-cheung. It was the closing film at the 19th Busan International Film Festival. It was released on 6 November.", "title": "" }, { "docid": "2251158", "text": "Captain Power and the Soldiers of the Future is a 1987–88 Canadian-American science fiction/action television series, merging live action with animation based on computer-generated images, that ran for 22 episodes in Canadian and American syndication. A toy line was also produced by Mattel, and during each episode there was a segment that included visual and audio material which interacted with the toys. A production of \"The Landmark Entertainment Group,\" \"Captain Power and the Soldiers of the Future\" was created by Gary Goddard and Anthony \"Tony\" Christopher (neither of whom actually wrote any of the stories) and developed by Marc Scott Zicree, with J. Michael Straczynski becoming de facto head writer. Plans to bring the series back, set 15 years after the first series, were announced in July 2016. Goddard’s Goddard Film Group, headed by Gary Goddard, one of the original series co-creators, is one of the development team of the new series.", "title": "" }, { "docid": "32045062", "text": "Pulaski is a neighborhood in eastern Gary, Indiana. It is roughly triangular in shape, bounded on the south by the Borman Expressway, on the west by Maryland Street, and on the northeast by the Norfolk Southern railway. It is separated by an industrial corridor from Aetna to its east and Emerson to its north; it directly adjoins the neighborhoods of Midtown and Glen Park. As of 2000, Pulaski's population was 6,777, which was 96.7% African-American, 1.4% white, and 1.3% of Hispanic ethnicity.", "title": "" }, { "docid": "54691438", "text": "This is a list of a horror films set primarily within or around academic institutions, including high schools, boarding schools, colleges, and university campuses. Film scholars have noted the prominence of educational institutions in the development of horror cinema, particularly in the subgenre of the slasher film. Critics such as Andrew Grunzke have cited the themes of bullying, sexuality, social acceptance, parent-child relationships, academic performance, and the development of morality during teenage and early adult life as primary reasons that many horror films have historically used the backdrop of high schools and colleges. Additionally, the universalization of education during the twentieth century, which coincided with the development of the horror film, helped foster a public audience for films set amongst students.", "title": "" }, { "docid": "703158", "text": "Johnnie To (born 22 April 1955), also known as To Kei-Fung (杜琪峯), is a Hong Kong film director and producer. Popular in his native Hong Kong, To has also found acclaim overseas. Intensely prolific, To has made films in a variety of genres, though in the West he is best known for his action and crime movies, which have earned him critical respect and a cult following (which include Quentin Tarantino, who once said that he really loves to watch To's gangster films).", "title": "" }, { "docid": "37434718", "text": "Astra is a 2012 Bengali film produced by Amit Agarwal and directed by Tathagata Bhattacherjee. This is an action film which revolves around the love story of a gangster. In this film, DaVinci Resolve — the latest colour grading software was used for the first time in an eastern India film.", "title": "" }, { "docid": "29039095", "text": "Fireman Sam In Action is a 1996 live-action stage play and a 62-minute film featuring three stories, \"Fire Station Flood Alert\", \"Dilys’ Attic Fire\" and \"Pontypandy Fireworks Party\". It was especially filmed for video, based on the Welsh stop-motion TV series, \"Fireman Sam\". The film was released on 1 April 1996 on BBC Video. The opening sequence of this film was filmed on location at Aldenham Country Park, Borehamwood, Hertfordshire, England. It features children from Parkside School learning fire safety with Fireman Sam played by Gary Lucas. The show, created by Paragraph International (based at Pinewood Studios) toured worldwide with Writer and Director, Charles Savage for 7 years along with a \"Postman Pat\" Musical .", "title": "" }, { "docid": "356304", "text": "Psychological horror is a subgenre of horror and psychological fiction that relies on mental, emotional and psychological states to frighten, disturb, or unsettle readers, viewers, or players. The subgenre frequently overlaps with the related subgenre of psychological thriller, and it often uses mystery elements and characters with unstable, unreliable, or disturbed psychological states to enhance the suspense, drama, action and horror of the setting and plot and to provide an overall unpleasant, unsettling, or distressing atmosphere.", "title": "" }, { "docid": "32321252", "text": "Thomas Elwood Knotts (1861–1921) was the first mayor of the city of Gary, Indiana, serving from 1909 to 1913, after having previously served as head of the Gary town board from 1906 to 1909. He was also Gary's first postmaster. His business ventures included the \"Gary Evening Post\", later merged into the \"Gary Post-Tribune\", and the Gary Trust & Savings Bank, both of which he founded in 1909.", "title": "" }, { "docid": "29331305", "text": "Guns, Girls and Gambling is a 2012 American action comedy thriller film written and directed by Michael Winnick. The film stars an ensemble cast, which includes Gary Oldman, Christian Slater, Megan Park, Helena Mattsson, Tony Cox, Chris Kattan, Powers Boothe and Jeff Fahey.", "title": "" }, { "docid": "32438858", "text": "Gangster Squad is a 2013 American action crime film directed by Ruben Fleischer, written by Will Beall and starring Josh Brolin, Ryan Gosling, Nick Nolte, Emma Stone and Sean Penn. The plot is a fictionalized account of the LAPD officers and detectives called the \"Gangster Squad\" who attempt to keep Los Angeles safe from Mickey Cohen and his gang during the 1940s and '50s.", "title": "" }, { "docid": "12395766", "text": "Lego \"Indiana Jones (stylized as LEGO \"Indiana Jones) is a Lego theme based on the \"Indiana Jones\" film franchise, licensed from Lucasfilm. The exclusive franchise (for the 'Construction Category Rights') was first announced in June 2007, and followed the successful Lego \"Star Wars\" franchise, also with Lucasfilm. The first set of products were launched in 2008, based upon two of the three earlier films (\"Raiders of the Lost Ark\" and \"The Last Crusade\"). Sets featuring scenes from the fourth film, \"Indiana Jones and the Kingdom of the Crystal Skull\", were released alongside the film, later in 2008. The \"Temple of Doom\" film was not featured until 2009, in a large set which re-created the mine-cart chase using new narrow-gauge Lego train track.", "title": "" }, { "docid": "20222480", "text": "The Show Must Go On () is a 2007 South Korean gangster-action dramedy film written and directed by Han Jae-rim, starring Song Kang-ho in the lead role. The film revolves around a full-time gangster who's aspiring to be a full-time husband and dad.", "title": "" }, { "docid": "46358676", "text": "Gangster Returns is a 2015 Bangladeshi action thriller film directed by Ashiqur Rahman and features Ziaul Faruq Apurba in lead role. The development began in January, 2013.", "title": "" } ]
7711	Can I profit from anticipating a drop in value?	[ { "docid": "140371", "text": "To expand on the comment made by @NateEldredge, you're looking to take a short position. A short position essentially functions as follows: Here's the rub: you have unlimited loss potential. Maybe you borrow a share and sell it at $10. Maybe in a month you still haven't closed the position and now the share is trading at $1,000. The share lender comes calling for their share and you have to close the position at $1,000 for a loss of $990. Now what if it was $1,000,000 per share, etc. To avoid this unlimited loss risk, you can instead buy a put option contract. In this situation you buy a contract that will expire at some point in the future for the right to sell a share of stock for $x. You get to put that share on to someone else. If the underlying stock price were to instead rise above the put's exercise price, the put will expire worthless — but your loss is limited to the premium paid to acquire the put option contract. There are all sorts of advanced options trades sometimes including taking a short or long position in a security. It's generally not advisable to undertake these sorts of trades until you're very comfortable with the mechanics of the contracts. It's definitely not advisable to take an unhedged short position, either by borrowing someone else's share(s) to sell or selling an option (when you sell the option you take the risk), because of the unlimited loss potential described above.", "title": "" }, { "docid": "397325", "text": "\"To summarize, there are three basic ways: (3) is the truly dangerous one. If there is a lot of short interest in a stock, but for some reason the stock goes up, suddenly a lot of people will be scrambling to buy that stock to cover their short position -- which will drive the price up even further, making the problem worse. Pretty soon, a bunch of smart rich guys will be poor guys who are suddenly very aware that they aren't as smart as they thought they were. Eight years ago, such a \"\"short squeeze\"\", as it's called, made the price of VW quadruple in two days. You could hear the Heinies howl from Hamburg to Haldenwanger. There are ways to protect yourself, of course. You can go short but also buy a call at a much higher price, thereby limiting your exposure, a strategy called a \"\"straddle\"\", but you also reduce your profit if you guessed right. It comes down to, as it always does, do you want to eat well, or to sleep well?\"", "title": "" }, { "docid": "24563", "text": "Purchasing an option to sell the stock is probably the safest bet. This gives you reasonable leverage, and your risk is limited to the cost of the option. Say the stock currently sells for $100 per share. You think it will drop to $80 per share in the next two weeks and the market thinks the price will be stable. Now, consider an option to sell one share of that stock for $95 any time within the next two weeks. The market would consider that option nearly worthless, since in all likelihood, you would lose out by exercising it (since you could just sell the share on the market for a price expected to be higher than that). You might be able to acquire that option for $5. Now, say you're right and within two weeks, the price drops to $80. Now you can purchase a share for $80, exercise the option to sell it for $95, and pocket $15. That would make you a $10 profit on a $5 investment. If you're wrong, you just let the option lapse and are out $5. No problem. In reality, you would buy a number of such options. And you wouldn't actually buy a share and exercise the option, you would just sell the option back to its issuer for $15.", "title": "" } ]	[ { "docid": "317363", "text": "\"In a rational market, the market caps (total value of all shares of the company) should be determined by the expected future profits of the company, plus the book value (that is the value of all assets that the company holds). The share price is then calculated as market caps divided by number of shares - a company worth a billion dollar could have a million shares at $1000 each or a billion shares at $1 each or anything in between. When profits drop, every investor has to re-think what the expected future profits of the company are. If all the investors say \"\"I thought this company would make a billion profit in the next ten years, but based on the drop in profits I changed my mind and I think they will only make 500 million\"\", then the share price drops. On the other hand, if profits dropped because of some predictable event, then that drop was already priced into the share price. If the profits dropped less than expected, the share price might even go up. You can see the opposite effect: Share price might be very high because everyone expects huge growth in profits over the next ten years. If profits grow less than expected, the share price will drop. Share price depends on predicted future profits, not on profits today.\"", "title": "" }, { "docid": "21457", "text": "Given that utilizing all the funds available to you drains your retirement and leaves you with very little cushion for unforeseen events (as already noted), it may be best to use a smaller amount for closing and just deal with the PMI for a couple years. PMI is likely less than the taxes/penalties incurred from withdrawing a full 20% + closing costs. Let alone the lost earning on the accounts (above your mortgage interest rate); but personally I think the stability of significant home equity is worth more than anticipated stock gains. I would recommend pulling enough to buy the house comfortably without dipping too deeply in any one area, while still paying down your balance to where you can eliminate PMI quickly (say 2-3 years). Your limits for each account are approximately: Roth IRAs: Traditional IRAs: Brokerage (non-retirement): Checking: Things to consider: If you are current on your payments, you can request PMI removal once your loan-to-value drops below 80% - it also terminates automatically when it is scheduled to drop below 78% (not if it actually has). Many loans have a 2 year minimum PMI period though, regardless of your Loan To Value (LTV) changes. LTV changes could be from:", "title": "" }, { "docid": "501838", "text": "Yield can be thought of as the interest rate you would receive from that investment in the form of a dividend for stocks or interest payments on a bond. The yield takes into account the anticipated amount to be received per share/unit per year and the current price of the investment. Of course, the yield is not a guaranteed return like a savings account. If the investment yield is 4% when you buy, it can drop in value such that you actually lose money during your hold period, despite receiving income from the dividend or interest payments.", "title": "" }, { "docid": "461483", "text": "\"The ultimate purpose of Case-Schiller is to build contracts that you can use to stop worrying about this, for a price. You or your lender might buy cash settled put options based on the index, and hope that if your home falls in value, the your options become \"\"in the money\"\" to make up the shortfall. The major problem that I can see with this is finding people to take the other side of that contract. Renters would be the primary candidates, but Americans are on average so overweight in real estate that there really isn't anyone underexposed to real estate who would benefit from diversification, and the tax advantage will give people far cheaper avenues address this. Viewed in this light, your question has a sort of obvious answer: Case-Schiller is historical data, and you need to know about the future historical data. Case-Schiller can't do it alone, but you can use futures markets to predict it. Problem you'll have is that the market itself will optimize this temporal trade: if there's a market drop anticipated, the market will charge you more for market drop insurance.\"", "title": "" }, { "docid": "55985", "text": "Generally, you need something that goes up over time during periods of index decline, but otherwise holds some value. Historically, people tend to use gold for that purpose. But with gold also set up for possible declines, that raises questions. Silver has dropped a bit more than gold in terms of percentages. If you think the downward motion will be in the form of sudden jumps, you can look at putting some of your money in puts away from the current price, but you can easily wind up paying too much for this protection. In the case of a deflation, most things lose value vs. money, and you want all cash. These things might already be obvious. I don't think there is a clear answer to your question. But if the future were clear, the present market could possibly anticipate and adjust... one reason the future of the market always seems a bit murky.", "title": "" }, { "docid": "137852", "text": "I think the advice Bob is being given is good. Bob shouldn't sell his investments just because their price has gone down. Selling cheap is almost never a good idea. In fact, he should do the opposite: When his investments become cheaper, he should buy more of them, or at least hold on to them. Always remember this rule: Buy low, sell high. This might sound illogical at first, why would someone keep an investment that is losing value? Well, the truth is that Bob doesn't lose or gain any money until he sells. If he holds on to his investments, eventually their value will raise again and offset any temporary losses. But if he sells as soon as his investments go down, he makes the temporary losses permanent. If Bob expects his investments to keep going down in the future, naturally he feels tempted to sell them. But a true investor doesn't try to anticipate what the market will do. Trying to anticipate market fluctuations is speculating, not investing. Quoting Benjamin Graham: The most realistic distinction between the investor and the speculator is found in their attitude toward stock-market movements. The speculator's primary interest lies in anticipating and profiting from market fluctuations. The investor's primary interest lies in acquiring and holding suitable securities at suitable prices. Market movements are important to him in a practical sense, because they alternately create low price levels at which he would be wise to buy and high price levels at which he certainly should refrain from buying and probably would be wise to sell. Assuming that the fund in question is well-managed, I would refrain from selling it until it goes up again.", "title": "" }, { "docid": "215118", "text": "\"Bull means the investor is betting on a rising market. Puts are a type of stock option where the seller of a put option promises to buy 100 shares of stock from the buyer of the put option at a pre-agreed price called the strike price on any day before expiration day. The buyer of the put option does not have to sell (it is optional, thats why it is called buying an option). However, the seller of the put is required to make good on their promise to the buyer. The broker can require the seller of the put option to have a deposit, called margin, to help make sure that they can make good on the promise. Profit... The buyer can profit from the put option if the stock price moves down substantially. The buyer of the put option does not need to own the stock, he can sell the option to someone else. If the buyer of the put option also owns the stock, the put option can be thought of like an insurance policy on the value of the stock. The seller of the put option profits if the stock price stays the same or rises. Basically, the seller comes out best if they can sell put options that no one ends up using by expiration day. A spread is an investment consisting of buying one option and selling another. Let's put bull and put and spread together with an example from Apple. So, if you believed Apple Inc. AAPL (currently 595.32) was going up or staying the same through JAN you could sell the 600 JAN put and buy the 550 put. If the price rises beyond 600, your profit would be the difference in price of the puts. Let's explore this a little deeper (prices from google finance 31 Oct 2012): Worst Case: AAPL drops below 550. The bull put spread investor owes (600-550)x100 shares = $5000 in JAN but received $2,035 for taking this risk. EDIT 2016: The \"\"worst case\"\" was the outcome in this example, the AAPL stock price on options expiry Jan 18, 2013 was about $500/share. Net profit = $2,035 - $5,000 = -$2965 = LOSS of $2965 Best Case: AAPL stays above 600 on expiration day in JAN. Net Profit = $2,035 - 0 = $2035 Break Even: If AAPL drops to 579.65, the value of the 600 JAN AAPL put sold will equal the $2,035 collected and the bull put spread investor will break even. Commissions have been ignored in this example.\"", "title": "" }, { "docid": "370760", "text": "\"I don't know why there is so much confusion on such a simple concept. The answer is very simple. A stock must eventually pay dividends or the whole stock market is just a cheap ponzi scheme. A company may temporarily decided to reinvest profits into R&D, company expansion, etc. but obviously if they promised to never pay dividends then you can never participate in the profits of the company and there is simply no intrinsic value to the stock. For all of you saying 'Yeah but the stock price will go up!', please people get a life. The only reason the price goes up is in anticipation of dividend yield otherwise WHY would the price go up? \"\"But the company is worth more and the stock is worth more\"\" A stocks value is not set by the company but by people who buy and sell in the open market. To think a stock's price can go up even if the company refuses to pay dividends is analogous to : Person A says \"\"Hey buy these paper clips for $10\"\". But those paper clips aren't worth that. \"\"It doesn't matter because some fool down the line will pay $15\"\". But why would they pay that? \"\"Because some fool after him will pay $20\"\" Ha Ha!\"", "title": "" }, { "docid": "31244", "text": "There's really not a simple yes/no answer. It depends on whether you're doing short term trading or long term investing. In the short term, it's not much different from sports betting (and would be almost an exact match if the bettors also got a percentage of the team's ticket sales), In the long term, though, your profit mostly comes from the growth of the company. As a company - Apple, say, or Tesla - increases sales of iPhones or electric cars, it either pays out some of the income as dividends, or invests them in growing the company, so it becomes more valuable. If you bought shares cheaply way back when, you profit from this increase when you sell them. The person buying it doesn't lose, as s/he buys at today's market value in anticipation of continued growth. Of course there's a risk that the value will go down in the future instead of up. Of course, there are also psychological factors, say when people buy Apple or Tesla because they're popular, instead of at a rational valuation. Or when people start panic-selling, as in the '08 crash. So then their loss is your gain - assuming you didn't panic, of course :-)", "title": "" }, { "docid": "226496", "text": "It's actually quite simple. You're actually confusing two concept. Which are taking a short position and short selling itself. Basically when taking a short position is by believing that the stock is going to drop and you sell it. You can or not buy it back later depending on the believe it grows again or not. So basically you didn't make any profit with the drop in the price's value but you didn't lose money either. Ok but what if you believe the market or specific company is going to drop and you want to profit on it while it's dropping. You can't do this by buying stock because you would be going long right? So back to the basics. To obtain any type of profit I need to buy low and sell high, right? This is natural for use in long positions. Well, now knowing that you can sell high at the current moment and buy low in the future what do you do? You can't sell what you don't have. So acquire it. Ask someone to lend it to you for some time and sell it. So selling high, check. Now buying low? You promised the person you would return him his stock, as it's intangible he won't even notice it's a different unit, so you buy low and return the lender his stock. Thus you bought low and sold high, meaning having a profit. So technically short selling is a type of short position. If you have multiple portfolios and lend yourself (i.e. maintaining a long-term long position while making some money with a short term short-term strategy) you're actually short selling with your own stock. This happens often in hedge funds where multiple strategies are used and to optimise the transaction costs and borrowing fees, they have algorithms that clear (match) long and short coming in from different traders, algorithms, etc. Keep in mind that you while have a opportunities risk associated. So basically, yes, you need to always 'borrow' a product to be able to short sell it. What can happen is that you lend yourself but this only makes sense if:", "title": "" }, { "docid": "598184", "text": "Let's use an example: You buy 10 machines for 100k, and those machines produce products sold for a total of 10k/year in profit (ignoring labor/electricity/sales costs etc). If the typical investor requires a rate of return of 10% on this business, your company would be worth 100k. In investing terms, you would have a PE ratio of 10. The immediately-required return will be lower if substantially greater returns are expected in the future (expected growth), and the immediately required return will be higher if your business is expected to shrink. If at the end of the year you take your 10k and purchase another machine, your valuation will rise to 110k, because you can now produce 11k in earnings per year. If your business has issued 10,000 shares, your share price will rise from $10 to $11. Note that you did not just put cash in the bank, and that you now have a higher share price. At the end of year 2, with 11 machines, lets imagine that customer demand has fallen and you are forced to cut prices. You somehow produce only 10k in profit, instead of the anticipated 11k. Investors believe this 10k in annual profit will continue into the forseable future. The investor who requires 10% return would then only value your company at 100k, and your share price would fall back from $11 to $10. If your earnings had fallen even further to 9k, they might value you at 90k (9k/0.1=$90k). You still have the same machines, but the market has changed in a way that make those machines less valuable. If you've gone from earning 10k in year one with 10 machines to 9k in year two with 11 machines, an investor might assume you'll make even less in year three, potentially only 8k, so the value of your company might even fall to 80k or lower. Once it is assumed that your earnings will continue to shrink, an investor might value your business based on a higher required rate of return (e.g. maybe 20% instead of 10%), which would cause your share price to fall even further.", "title": "" }, { "docid": "63296", "text": "\"If so, then if company A never pays dividends to its shareholders, then what is the point of owning company A's stock? The stock itself can go up in price. This is not necessarily pure speculation either, the company could just reinvest the profits and grow. Since you own part of a company, your share would also increase in value. The company could also decide to start paying dividend. I think one rule of thumb is that growing companies won't pay out, since they reinvest all profit to grow even more, but very large companies like McDonalds or Microsoft who don't really have much room left to grow will pay dividends more. Surely the right to one vote for company A's Board can't be that valuable. Actually, Google for instance neither pays dividend nor do you get to vote. Basically all you get for your money is partial ownership of the company. This still gives you the right to seize Google assets if you go bankrupt, if there's any asset left once the creditors are done (credit gets priority over equity). What is it that I'm missing? What you are missing is that the entire concept of the dividend is an illusion. There's little qualitative difference between a stock that pays dividend, and a stock that doesn't. If you were going to buy the stock, then hold it forever and collect dividend, you could get the same thing with a dividend-less stock by simply waiting for it to gain say 5% value, then sell 4.76% of your stock and call the cash your dividend. \"\"But wait,\"\" you say, \"\"that's not the same - my net worth has decreased!\"\" Guess what, stocks that do pay dividend usually do drop in value right after the pay out, and they drop by about the relative value of the dividend as well. Likewise, you could take a stock that does pay dividend, and make it look exactly like a non-paying stock by simply taking every dividend you get and buying more of the same stock with it. So from this simplistic point of view, it is irrelevant whether the stock itself pays dividend or not. There is always the same decision of whether to cut the goose or let it lay a few more eggs that every shareholder has to make it. Paying a dividend is essentially providing a different default choice, but makes little difference with regards to your choices. There is however more to it than simple return on investment arithmetic: As I said, the alternative to paying dividend is reinvesting profits back into the enterprise. If the company decided to pay out dividend, that means they think all the best investing is done, and they don't really have a particularly good idea for what to do with the extra money. Conversely, not paying is like management telling the shareholders, \"\"no we're not done, we're still building our business!\"\". So it can be a way of judging whether the company is concentrating on generating profit or growing itself. Needless to say the, the market is wild and unpredictable and not everyone obeys such assumptions. Furthermore, as I said, you can effectively overrule the decision by increasing or decreasing your position, regardless of whether they have decided to pay dividend to begin with. Lastly, there may be some subtle differences with regards to things like how the income is taxed and so on. These don't really have much to do with the market itself, but the bureaucracy tacked onto the market.\"", "title": "" }, { "docid": "336018", "text": "\"Learn something new every day... I found this interesting and thought I'd throw my 2c in. Good description (I hope) from Short Selling: What is Short Selling First, let's describe what short selling means when you purchase shares of stock. In purchasing stocks, you buy a piece of ownership in the company. You buy/sell stock to gain/sell ownership of a company. When an investor goes long on an investment, it means that he or she has bought a stock believing its price will rise in the future. Conversely, when an investor goes short, he or she is anticipating a decrease in share price. Short selling is the selling of a stock that the seller doesn't own. More specifically, a short sale is the sale of a security that isn't owned by the seller, but that is promised to be delivered. Still with us? Here's the skinny: when you short sell a stock, your broker will lend it to you. The stock will come from the brokerage's own inventory, from another one of the firm's customers, or from another brokerage firm. The shares are sold and the proceeds are credited to your account. Sooner or later, you must \"\"close\"\" the short by buying back the same number of shares (called covering) and returning them to your broker. If the price drops, you can buy back the stock at the lower price and make a profit on the difference. If the price of the stock rises, you have to buy it back at the higher price, and you lose money. So what happened? The Plan The Reality Lesson I never understood what \"\"Shorting a stock\"\" meant until today. Seems a bit risky for my blood, but I would assume this is an extreme example of what can go wrong. This guy literally chose the wrong time to short a stock that was, in all visible aspects, on the decline. How often does a Large Company or Individual buy stock on the decline... and send that stock soaring? How often does a stock go up 100% in 24 hours? 600%? Another example is recently when Oprah bought 10% of Weight Watchers and caused the stock to soar %105 in 24 hours. You would have rued the day you shorted that stock - on that particular day - if you believed enough to \"\"gamble\"\" on it going down in price.\"", "title": "" }, { "docid": "273789", "text": "I'm not entirely sure about some of the details in your question, since I think you meant to use $10,000 as the value of the futures contract and $3 as the value of the underlying stock. Those numbers would make more sense. That being said, I can give you a simple example of how to calculate the profit and loss from a leveraged futures contract. For the sake of simplicity, I'll use a well-known futures contract: the E-mini S&P500 contract. Each E-mini is worth $50 times the value of the S&P 500 index and has a tick size of 0.25, so the minimum price change is 0.25 * $50 = $12.50. Here's an example. Say the current value of the S&P500 is 1,600; the value of each contract is therefore $50 * 1,600 = $80,000. You purchase one contract on margin, with an initial margin requirement1 of 5%, or $4,000. If the S&P 500 index rises to 1,610, the value of your futures contract increases to $50 * 1,610 = $80,500. Once you return the 80,000 - 4,000 = $76,000 that you borrowed as leverage, your profit is 80,500 - 76,000 = $4,500. Since you used $4,000 of your own funds as an initial margin, your profit, excluding commissions is 4,500 - 4,000 = $500, which is a 500/4000 = 12.5% return. If the index dropped to 1,580, the value of your futures contract decreases to $50 * 1,580 = $79,000. After you return the $76,000 in leverage, you're left with $3,000, or a net loss of (3,000 - 4000)/(4000) = -25%. The math illustrates why using leverage increases your risk, but also increases your potential for return. Consider the first scenario, in which the index increases to 1,610. If you had forgone using margin and spent $80,000 of your own funds, your profit would be (80,500 - 80,000) / 80000 = .625%. This is smaller than your leveraged profit by a factor of 20, the inverse of the margin requirement (.625% / .05 = 12.5%). In this case, the use of leverage dramatically increased your rate of return. However, in the case of a decrease, you spent $80,000, but gained $79,000, for a loss of only 1.25%. This is 20 times smaller in magnitude than your negative return when using leverage. By forgoing leverage, you've decreased your opportunity for upside, but also decreased your downside risk. 1) For futures contracts, the margin requirements are set by the exchange, which is CME group, in the case of the E-mini. The 5% in my example is higher than the actual margin requirement, which is currently $3,850 USD per contract, but it keeps the numbers simple. Also note that CME group refers to the initial margin as the performance bond instead.", "title": "" }, { "docid": "90073", "text": "Stock prices reflect future expectations of large groups of people, and may not be directly linked to traditional valuations for a number of reasons (not definitive). For example, a service like Twitter is so popular that even though it has no significant revenue and loses money, people are simply betting that it is deeply embedded enough that it will eventually find some way to make money. You can also see a number of cases of IPOs of various types of companies that do not even have a revenue model at all. Also, if there is rapid sales growth in A but B sales are flat, no one is likely to expect future profit growth in B such that the valuation will remain steady. If sales in A are accelerating, there may be anticipation that future profits will be high. Sometimes there are also other reasons, such as if A owns valuable proprietary assets, that will hold the values up. However, more information about these companies' financials is really needed in order to understand why this would be the case.", "title": "" }, { "docid": "204297", "text": "\"I interned for about six months at a firm that employed a few technical analysts, so I'll try to provide what little information I can. Since the bulk of the intra-day trading was decided algorithmically, technical analysts had two main functions: This basically boils down to my answer to your question. There are still enough people, trading firms, etc. who believe in candlestick charting and other visually subjective patterns that if you notice a trend, pattern, etc. before the majority of traders observing, you may be able to time the market successfully and profit. This is becoming increasingly dangerous, however, because of the steps I outlined above. Over time, the charting patterns that have been proven effective (often in many firms individually since the algorithms are all proprietary) are incorporated into computer algorithms, so the \"\"traders\"\" you're competing with to see the pattern are increasingly low-latency computer clusters less than a few blocks from the exchange. Summary: Candlestick charting, along with other forms of subjective technical analysis, has its believers, and assuming enough of these believers trade the standard strategies based on the standard patterns, one could conceivably time the market with enough skill to anticipate these traders acting on the pattern and therefore profit. However, the marginal benefits of doing so are decreasing rapidly as computers take over more trading responsibility. Caveats: I know you're in Australia, where the market penetration of HF/algo traders isn't as high as in the US, so it might be a few more years before the marginal benefits cease to be profitable; that being said, if various forms of technical analysis proved wildly profitable in Australia, above and beyond profits available in other markets, rest assured that large American or British trading firms would already have moved in. My experience is limited to one trading firm, so I certainly can't speak for the industry as a whole. I know I didn't address candlestick charts specifically, but since they're only one piece of visual technical analysis, I tried to address the issue as a whole. This somewhat ties into the debate between fundamental or technical analysis, which I won't get into. Investopedia has a short article on the subject. As I said, I won't get into this because while it's a nice debate for small traders, at large trading firms, they don't care; they want to make profit, and any strategy that can be vetted, whether it's fundamental, technical, or astrological, will be vetted. I want to add more information to my answer to clear up some of the misconceptions in the comments, including those talking about biased studies and a lack of evidence for or against technical analysis (and candlestick charts; I'll explore this relationship further down). It's important to keep in mind that charting methods, including candlestick charts, are visually subjective ways of representing data, and that any interpretations drawn from such charts should, ideally, represent objective technical indicators. A charting method is only as good as the indicators it's used to represent. Therefore, an analysis of the underlying indicators provides a suitable analysis for the visual medium in which they're presented. One important study that evaluates several of these indicators is Foundations of Technical Analysis: Computational Algorithms, Statistical Inference, and Empirical Implementation by Lo, Mamaysky, and Wang. Lest anyone accuse its authors of bias, I should point out that not only is it published by the National Bureau of Economic Research (a highly reputable organization within economics and finance), but also that the majority of its authors come from MIT's Sloan school, which holds a reputation second to none. This study finds that several technical indicators, e.g. head-and-shoulder, double-bottom, and various rectangle techniques, do provide marginal value. They also find that although human judgment is still superior to most computational algorithms in the area of visual pattern recognition, ... technical analysis can be improved by using automated algorithms Since this paper was published in 2000, computing power and statistical analysis have gained significant ground against human ability to identify and exploit for visual pattern detection like candlestick charts. Second, I suggest you look into David Aaronson's book, Evidence-Based Technical Analysis: Applying the Scientific Method and Statistical Inference to Trading Signals. He finds similar results to the Lo, et. al. paper, in that some technical indicators do add value to the investment process, but those that do are those that can be represented mathematically and thus programmed directly into trading algorithms (thus bypassing visual tools like candlestick charts). He describes how studies, including Lo, et al., have found that head and shoulders patterns are worse than random, i.e. you would earn higher returns if you simply traded at random. That point is worth than repeating. If a day-trader is using a candlestick chart and using head-and-shoulders patterns as part of their toolkit, he's rolling the dice when he uses that pattern and returns that come from its application come from chance. This reminds me of that old story about a company that sends out pamphlets predicting the results of sports games, complete with \"\"strategies\"\" and \"\"data\"\" to back up the predictions. The company sends out several versions of the pamphlet every game, each predicting a different winner. Given a large enough sample size, by the end of the season, there are a few people who have received a pamphlet that accurately predicted the winner for every game and they're convinced the system is perfect. The others weren't so lucky, however. Relying on candlestick charts and TA patterns that are relics from the pre-computerized era is reassuring to some traders and gives them a sense of control and \"\"beating the market,\"\" but how long will chance remain on your side? This is why I maintain that visual tools like candlestick charts are a slowly dying medium. They certainly still add value to some trading firms, which is why Bloomberg terminals still ship with this functionality built in, but as more and more research shows, automated algorithms and statistical indicators can provide more value. It's also important to think about whether the majority of the value added by visual tools like candlestick charts comes in the form of profit or a sense of security to traders who learned the field using them over the past few decades. Finally, it's extremely important to realize that the actions of retail investors in the equities market cannot begin to represent the behaviors of the market as a whole. In the equities markets alone, trading firms and institutional investors dwarf retail investors, and the difference in scale is even more vastly pronounced in derivatives and currency markets. The fact that some retail investors use candlestick charts and the technical indicators they (hope) underlie them provides nothing but minor anecdotal evidence as to their effectiveness.\"", "title": "" }, { "docid": "181434", "text": "As I understand it, the correct price is any point between the minimum the seller is willing to accept and the maximum the buyer is willing to pay. These values are influenced by a number of factors, including market conditions, cost of production and immediate need. There's also a sense of fairness and expectation that influences these numbers. People don't want to pay a much higher price or accept a much lower price than they think the other party should agree to. For example, in the event of a sudden actual or anticipated shortage in some commodity consumer good, say... gasoline, it would make sense for sellers to raise the price significantly. In the short term, consumers of gasoline are very price-insensitive and most will pay more than double the usual price to obtain it. This behavior is commonly seen as unfair on the part of the seller - to the point that certain variations of it are illegal in some jurisdictions. Economists would describe it as rational. Oddly, people don't seem to be as upset about buyers offering low prices in the event of a sudden increase in highly motivated sellers. When people do tend to get upset is if the buyers have a profit motive; they know the price decrease is temporary and are willing to buy and hold the asset to make a profit later. Even so, it seems to me that it's much rarer for such behavior to be illegal. The underlying objection, as far as I can tell is to what is perceived as greed.", "title": "" }, { "docid": "296959", "text": "Yeah and Doctor Oz has a medical degree. There's a whole lot of skepticism and critique of the outdated and abandoned methods he's using. A quick google search will say from plenty of other experts from MIT and other name dropping schools that his data isn't and cannot be realistic. I'm anticipating a market correction, but I'm also not a conspiracy theorist.", "title": "" }, { "docid": "176254", "text": "The earlier answers answered the question on how a more practical trader can lose money. Here I'd like to mention some obtuse ways Using debt to buy stocks. If one is borrowing at a higher rate than they are getting back, from an economics prospective their stocks are losing money even if the value of those stocks are going up. Using debt to buy stocks. I'll simplify the nightmare situation. I know someone who has Y dollars of cash. Their broker will loan them X. With their X+Y money, they purchase some equities through the broker. The agreement of the loan is that if the value of those equities drops below a certain percentage of the outstanding debt (ex 150%), the broker will automatically and without notification, sell some equities indiscriminately to reduce the outstanding debt. Being in high-interest debt but buying stocks. There are millions of people who are paying 15+% interest rates on consumer debt while investing and getting 5% returns or less on average. Similar to an earlier point, from an economics prospective the choice to buy equities is a profit losing choice.", "title": "" }, { "docid": "20335", "text": "\"The textbook answer would be \"\"assets-liabilities+present discounted value of all future profit\"\". A&L is usually simple (if a company has an extra $1m in cash, it's worth $1m more; if it has an extra $1m in debt, it's worth $1m less). If a company with ~0 assets and $50k in profit has a $1m valuation, then that implies that whoever makes that valuation (wants to buy at that price) really believes one of two things - either the future profit will be significantly larger than $50k (say, it's rapidly growing); or the true worth of assets is much more - say, there's some IP/code/patents/people that have low book value but some other company would pay $1m just to get that. The point is that valuation is subjective since the key numbers in the calculations are not perfectly known by anyone who doesn't have a time machine, you can make estimates but the knowledge to make the estimates varies (some buyers/sellers have extra information), and they can be influenced by those buyers/sellers; e.g. for strategic acquisitions the value of company is significantly changed simply because someone claims they want to acquire it. And, $1m valuation for a company with $500m in profits isn't appropriate - it's appropriate only if the profits are expected to drop to zero within a couple years; a stagnant but stable company with $500m profits would be worth at least $5m and potentially much more.\"", "title": "" }, { "docid": "139094", "text": "\"They are similar in the sense that they are transferring money from the company to shareholders, but that's about it. There is different tax treatment, yes, but that's because they are fundamentally different. Dividends transfer money equally to all shareholders, but that also reduces the value of each share by the same amount, since it's cash out the door, which drops the value of the company. Shareholders are taxed on dividends at the capital gains tax rate. A buyback returns the cash to shareholders who decide to sell. Other shareholders get a secondary benefit of now owning a slightly larger portion of the company since there are fewer shares outstanding. Shareholders only pay tax if they sell shares for a gain. It that means when company buyback their stock, the stock price will definitely go up? Not necessarily. It depends on the price that the company buys back the shares for and what the \"\"opportunity cost\"\" of that cash is - meaning what else could the company have done with the cash that would have been better? Buybacks often happen in mature companies with undervalued stock prices and fewer opportunities for further investment. If a company has an intrinsic value of $10 a share but its stock is trading at $8 a share, then it can instantly get a 25% \"\"return\"\" by buying back stock. I use the term \"\"return\"\" loosely since the company does not actually profit from the buyback, but from the shareholder's perspective the company is worth more per share.\"", "title": "" }, { "docid": "428399", "text": "An option gives you the option rather than the obligation to buy (or sell) the underlying so you don't have to exercise you can just let the option expire (so long it doesn't have an automatic expiry). After expiration the option is worthless if it is out of the money but other than that has no hangover. Option prices normally drop as the time value of the option decays. An option has two values associated with it; time value and exercise value. Far out of the money (when the price of the underlying is far from the strike price on the losing side) options only have time value whereas deep in the money options (as yours seems to be) has some time value as well as the intrinsic value of the right to buy (sell) at a low (high) price and then sell (buy) the underlying. The time value of the option comes from the possibility that the price of the underlying will move (further) in your favour and make you more money at expiry. As expiry closes it is less likely that there will be a favourable mood so this value declines which can cause prices to move sharply after a period of little to no revaluing. Up to now what I have said applies to both OTC and traded options but exchange traded options have another level of complexity in their trading; because there are fewer traders in the options market the size of trade at which you can move the market is much lower. On the equities markets you may need to trade millions of shares to have be substantial enough to significantly move a price, on the options markets it could be thousands or even hundreds. If these are European style options (which sounds likely) and a single trading entity was holding a large number of the exchange traded options and now thinks that the price will move significantly against them before expiry their sell trade will move the market lower in spite of the options being in the money. Their trade is based on their supposition that by the time they can exercise the option the price will be below the strike and they will lose money. They have cashed out at a price that suited them and limited what they will lose if they are right about the underlying. If I am not correct in my excise style assumption (European) I may need more details on the trade as it seems like you should just exercise now and take the profit if it is that far into the money.", "title": "" }, { "docid": "566205", "text": "\"I'm not a financial expert, but saying that paying a $1 dividend will reduce the value of the stock by $1 sounds like awfully simple-minded reasoning to me. It appears to be based on the assumption that the price of a stock is equal to the value of the assets of a company divided by the total number of shares. But that simply isn't true. You don't even need to do any in-depth analysis to prove it. Just look at share prices over a few days. You should easily be able to find stocks whose price varied wildly. If, say, a company becomes the target of a federal investigation, the share price will plummet the day the announcement is made. Did the company's assets really disappear that day? No. What's happened is that the company's long term prospects are now in doubt. Or a company announces a promising new product. The share price shoots up. They may not have sold a single unit of the new product yet, they haven't made a dollar. But their future prospects now look improved. Many factors go into determining a stock price. Sure, total assets is a factor. But more important is anticipated future earning. I think a very simple case could be made that if a stock never paid any dividends, and if everyone knew it would never pay any dividends, that stock is worthless. The stock will never produce any profit to the owner. So why should you be willing to pay anything for it? One could say, The value could go up and you could sell at a profit. But on what basis would the value go up? Why would investors be willing to pay larger and larger amounts of money for an asset that produces zero income? Update I think I understand the source of the confusion now, so let me add to my answer. Suppose that a company's stock is selling for, say, $10. And to simplify the discussion let's suppose that there is absolutely nothing affecting the value of that stock except an expected dividend. The company plans to pay a dividend on a specific date of $1 per share. This dividend is announced well in advance. Everyone knows that it will be paid, and everyone is extremely confidant that in fact the company really will pay it -- they won't run out of money or any such. Then in a pure market, we would expect that as the date of that dividend approaches, the price of the stock would rise until the day before the dividend is paid, it is $11. Then the day after the dividend is paid the price would fall back to $10. Why? Because the person who owns the stock on the \"\"dividend day\"\" will get that $1. So if you bought the stock the day before the dividend, the next day you would immediately receive $1. If without the dividend the stock is worth $10, then the day before the dividend the stock is worth $11 because you know that the next day you will get a $1 \"\"refund\"\". If you buy the stock the day after the dividend is paid, you will not get the $1 -- it will go to the person who had the stock yesterday -- so the value of the stock falls back to the \"\"normal\"\" $10. So if you look at the value of a stock immediately after a dividend is paid, yes, it will be less than it was the day before by an amount equal to the dividend. (Plus or minus all the other things that affect the value of a stock, which in many cases would totally mask this effect.) But this does not mean that the dividend is worthless. Just the opposite. The reason the stock price fell was precisely because the dividend has value. BUT IT ONLY HAS VALUE TO THE PERSON WHO GETS IT. It does me no good that YOU get a $1 dividend. I want ME to get the money. So if I buy the stock after the dividend was paid, I missed my chance. So sure, in the very short term, a stock loses value after paying a dividend. But this does not mean that dividends in general reduce the value of a stock. Just the opposite. The price fell because it had gone up in anticipation of the dividend and is now returning to the \"\"normal\"\" level. Without the dividend, the price would never have gone up in the first place. Imagine you had a company with negligible assets. For example, an accounting firm that rents office space so it doesn't own a building, its only tangible assets are some office supplies and the like. So if the company liquidates, it would be worth pretty much zero. Everybody knows that if liquidated, the company would be worth zero. Further suppose that everyone somehow knows that this company will never, ever again pay a dividend. (Maybe federal regulators are shutting the company down because it's products were declared unacceptably hazardous, or the company was built around one genius who just died, etc.) What is the stock worth? Zero. It is an investment that you KNOW has a zero return. Why would anyone be willing to pay anything for it? It's no answer to say that you might buy the stock in the hope that the price of the stock will go up and you can sell at a profit even with no dividends. Why would anyone else pay anything for this stock? Well, unless their stock certificates are pretty and people like to collect them or something like that. Otherwise you're supposing that people would knowingly buy into a pyramid scheme. (Of course in real life there are usually uncertainties. If a company is dying, some people may believe, rightly or wrongly, that there is still hope of reviving it. Etc.) Don't confuse the value of the assets of a company with the value of its stock. They are related, of course -- all else being equal, a company with a billion dollars in assets will have a higher market capitalization than a company with ten dollars in assets. But you can't calculate the price of a company's stock by adding up the value of all its assets, subtracting liabilities, and dividing by the number of shares. That's just not how it works. Long term, the value of any stock is not the value of the assets but the net present value of the total future expected dividends. Subject to all sorts of complexities in real life.\"", "title": "" }, { "docid": "316132", "text": "\"Of course it can. This is a time value of money calculation. If I knew the maturity date, or current yield to maturity I'd be able to calculate the other number and advise how much rates need to rise to cause the value to drop from 18 to 17. For a 10 year bond, a rise today of .1% will cause the bond to drop about 1% in value. This is a back of napkin calculation, finance calculators offer precision. edit - when I calculate present value with 34 years to go, and 5.832% yield to maturity, I get $14.55. At 5.932, the value drops to $14.09, a drop of 3.1%. Edit - Geo asked me to show calculations. Here it goes - A) The simplest way to calculate present value for a zero coupon bond is to take the rate 5.832%, convert it to 1.05832 and divide into the face value, $100. I offer this as the \"\"four function calculator\"\" approach, so one enters $100 divided by 1.05832 and repeat for the number of years left. A bit of precision is lost if there's a fractional year involved, but it's close. The bid/ask will be wider than this error introduced. B) Next - If you've never read my open declaration of love for my Texas Instruments BA-35 calculator, here it is, again. One enters N=34 (for the years) FV = 100, Rate = 5.832, and then CPT PV. It will give the result, $14.56. C) Here is how to do it in Excel - The numbers in lines 1-3 are self evident, the equation in cell B4 is =-PV(B3/100,B1,0,B2) - please note there are tiny differences in the way to calculate in excel vs a calculator. Excel wants the rate to be .05832, so I divided by 100 in the equation cell. That's the best 3 ways I know to calculate present value. Geo, if you've not noticed, the time value of money is near and dear to me. It comes into play for bonds, mortgages, and many aspect of investing. The equations get more complex if there are payments each year, but both the BA-35 and excel are up to it.\"", "title": "" }, { "docid": "261522", "text": "Like others have already said, it may cause an immediate dip due to a large and sudden move in shares for that particular stock. However, if there is nothing else affecting the company's financials and investors perceive no other risks, it will probably bounce back a bit, but not back to the full value before the shares were issued. Why? Whenever a company issues more stock, the new shares dilute the value of the current shares outstanding, simply because there are now more shares of that stock trading on the market; the Earnings Per Share (EPS) Ratio will drop since the same profit and company value has to be spread across more shares. Example: If a company is valued at $100 dollars and they have 25 shares outstanding, then the EPS ratio equates to $4 per share (100/25 = 4). If the company then issues more shares (stock to employees who sell or keep them), let's say 25 more shares, then shares outstanding increase to 50, but the company's value still remains at $100 dollars. EPS now equates to $2 per share (100/50 = 2). Now, sometimes when shareholders (especially employees...and especially employees who just received them) suddenly all sell their shares, this causes a micro-panic in the market because investors believe the employees know something bad about the company that they don't. Other common shareholders then want to dump their holdings for fear of impending collapse in the company. This could cause the share price to dip a bit below the new diluted value, but again if no real, immediate risks exist, the price should go back up to the new, diluted value. Example 2: If EPS was at $4 before issuing more stock, and then dropped to $2 after issuing new stock, the micro-panic may cause the EPS to drop below $2 and then soon rebound back to $2 or more when investors realize no actual risk exists. After the dilution phase plays out, the EPS could actually even go above the pre-issuing value of $4 because investors may believe that since more stock was issued due to good profits, more profits may ensue. Hope that helps!", "title": "" }, { "docid": "430570", "text": "\"Of course. The rationale is exactly the same as always: profit is taxed. The fact that you use intermediate barter to make that profit is irrelevant. To clarify, as it seems that you think it makes a difference that no money \"\"changed hands\"\". Consider this situation: So far your cost is $10000. How will the tax authority address this? They will look at the fair market value of the barter. You got gold worth of $20000. So from their perspective, you got $20000, and immediately exchanged it into gold. What does it mean for you? That you're taxed on the $10000 gain you made on your product X (the $20000 worth of barter that you received minus the $10000 worth of work/material/expenses that you spend on producing the merchandise), and that you have $20000 basis in the gold that you now own. If in a year, when you plan to sell the gold, its price drops - you can deduct investment losses. If its price goes up - you'll have investment gain. But for the gain you're making on your product X you will pay taxes now, because that's when you realized it - sold the merchandize and received in return something else of a value.\"", "title": "" }, { "docid": "150672", "text": ">Banks benefit from lower interest rates because it decreases the rate at which they can borrow from the Federal Reserve from. But what matters is the spread: if rates on the borrowing and lending side go down, the spread % shrinks, which makes banks less profitable. That's why bank stocks go up when higher rates are anticipated. You can think of a bank stock as being long interest rates. That's why bank stocks have lagged the rest of the market during this long bull market. >Bank's Assets aren't all debt The vast majority is for most banks. GS and MS are the rare exceptions.", "title": "" }, { "docid": "573077", "text": "\"Being \"\"Long\"\" something means you own it. Being \"\"Short\"\" something means you have created an obligation that you have sold to someone else. If I am long 100 shares of MSFT, that means that I possess 100 shares of MSFT. If I am short 100 shares of MSFT, that means that my broker let me borrow 100 shares of MSFT, and I chose to sell them. While I am short 100 shares of MSFT, I owe 100 shares of MSFT to my broker whenever he demands them back. Until he demands them back, I owe interest on the value of those 100 shares. You short a stock when you feel it is about to drop in price. The idea there is that if MSFT is at $50 and I short it, I borrow 100 shares from my broker and sell for $5000. If MSFT falls to $48 the next day, I buy back the 100 shares and give them back to my broker. I pocket the difference ($50 - $48 = $2/share x 100 shares = $200), minus interest owed. Call and Put options. People manage the risk of owning a stock or speculate on the future move of a stock by buying and selling calls and puts. Call and Put options have 3 important components. The stock symbol they are actionable against (MSFT in this case), the \"\"strike price\"\" - $52 in this case, and an expiration, June. If you buy a MSFT June $52 Call, you are buying the right to purchase MSFT stock before June options expiration (3rd Saturday of the month). They are priced per share (let's say this one cost $0.10/share), and sold in 100 share blocks called a \"\"contract\"\". If you buy 1 MSFT June $52 call in this scenario, it would cost you 100 shares x $0.10/share = $10. If you own this call and the stock spikes to $56 before June, you may exercise your right to purchase this stock (for $52), then immediately sell the stock (at the current price of $56) for a profit of $4 / share ($400 in this case), minus commissions. This is an overly simplified view of this transaction, as this rarely happens, but I have explained it so you understand the value of the option. Typically the exercise of the option is not used, but the option is sold to another party for an equivalent value. You can also sell a Call. Let's say you own 100 shares of MSFT and you would like to make an extra $0.10 a share because you DON'T think the stock price will be up to $52/share by the end of June. So you go to your online brokerage and sell one contract, and receive the $0.10 premium per share, being $10. If the end of June comes and nobody exercises the option you sold, you get to keep the $10 as pure profit (minus commission)! If they do exercise their option, your broker makes you sell your 100 shares of MSFT to that party for the $52 price. If the stock shot up to $56, you don't get to gain from that price move, as you have already committed to selling it to somebody at the $52 price. Again, this exercise scenario is overly simplified, but you should understand the process. A Put is the opposite of a Call. If you own 100 shares of MSFT, and you fear a fall in price, you may buy a PUT with a strike price at your threshold of pain. You might buy a $48 June MSFT Put because you fear the stock falling before June. If the stock does fall below the $48, you are guaranteed that somebody will buy yours at $48, limiting your loss. You will have paid a premium for this right (maybe $0.52/share for example). If the stock never gets down to $48 at the end of June, your option to sell is then worthless, as who would sell their stock at $48 when the market will pay you more? Owning a Put can be treated like owning insurance on the stock from a loss in stock price. Alternatively, if you think there is no way possible it will get down to $48 before the end of June, you may SELL a $48 MSFT June Put. HOWEVER, if the stock does dip down below $48, somebody will exercise their option and force you to buy their stock for $48. Imagine a scenario that MSFT drops to $30 on some drastically terrible news. While everybody else may buy the stock at $30, you are obligated to buy shares for $48. Not good! When you sold the option, somebody paid you a premium for buying that right from you. Often times you will always keep this premium. Sometimes though, you will have to buy a stock at a steep price compared to market. Now options strategies are combinations of buying and selling calls and puts on the same stock. Example -- I could buy a $52 MSFT June Call, and sell a $55 MSFT June Call. I would pay money for the $52 Call that I am long, and receive money for the $55 Call that I am short. The money I receive from the short $55 Call helps offset the cost of buying the $52 Call. If the stock were to go up, I would enjoy the profit within in $52-$55 range, essentially, maxing out my profit at $3/share - what the long/short call spread cost me. There are dozens of strategies of mixing and matching long and short calls and puts depending on what you expect the stock to do, and what you want to profit or protect yourself from. A derivative is any financial device that is derived from some other factor. Options are one of the most simple types of derivatives. The value of the option is derived from the real stock price. Bingo? That's a derivative. Lotto? That is also a derivative. Power companies buy weather derivatives to hedge their energy requirements. There are people selling derivatives based on the number of sunny days in Omaha. Remember those calls and puts on stock prices? There are people that sell calls and puts based on the number of sunny days in Omaha. Sounds kind of ridiculous -- but now imagine that you are a solar power company that gets \"\"free\"\" electricity from the sun and they sell that to their customers. On cloudy days, the solar power company is still on the hook to provide energy to their customers, but they must buy it from a more expensive source. If they own the \"\"Sunny Days in Omaha\"\" derivative, they can make money for every cloudy day over the annual average, thus, hedging their obligation for providing more expensive electricity on cloudy days. For that derivative to work, somebody in the derivative market puts a price on what he believes the odds are of too many cloudy days happening, and somebody who wants to protect his interests from an over abundance of cloudy days purchases this derivative. The energy company buying this derivative has a known cost for the cost of the derivative and works this into their business model. Knowing that they will be compensated for any excessive cloudy days allows them to stabilize their pricing and reduce their risk. The person selling the derivative profits if the number of sunny days is higher than average. The people selling these types of derivatives study the weather in order to make their offers appropriately. This particular example is a fictitious one (I don't believe there is a derivative called \"\"Sunny days in Omaha\"\"), but the concept is real, and the derivatives are based on anything from sunny days, to BLS unemployment statistics, to the apartment vacancy rate of NYC, to the cost of a gallon of milk in Maine. For every situation, somebody is looking to protect themselves from something, and somebody else believes they can profit from it. Now these examples are highly simplified, many derivatives are highly technical, comprised of multiple indicators as a part of its risk profile, and extremely difficult to explain. These things might sound ridiculous, but if you ran a lemonade stand in Omaha, that sunny days derivative just might be your best friend...\"", "title": "" }, { "docid": "280992", "text": "Here is a deliberately simple example of Dollar Cost averaging: Day 1: Buy 100 shares at $10. Total value = $1,000. Average cost per share = $10.00/share (easy). Day 2: Buy 100 more shares at $9. Total value = $1,900. Average cost per share = $9.50/share (1,900/200). Notice how your average cost per share went from $10.00 to $9.50. Now instead of hoping the stock rises above $10.00 a share to make a profit, you only need it to go to $9.50 a share (assuming no commissions or transaction fees). It's easy to see how this could work to your advantage. The only catch is that you need buy more of a stock that is dropping (people might think you're crazy). This could easily backfire if the stock continues to drop.", "title": "" }, { "docid": "577201", "text": "As Sean pointed out they usually mean LIBOR or the FFR (or for other countries the equivalent risk free rate of interest). I will just like to add on to what everyone has said here and will like to explain how various interest rates you mentioned work out when the risk free rate moves: For brevity, let's denote the risk free rate by Rf, the savings account interest rate as Rs, a mortgage interest rate as Rmort, and a term deposit rate with the bank as Rterm. Savings account interest rate: When a central bank revises the overnight lending rate (or the prime rate, repo rate etc.), in some countries banks are not obliged to increase the savings account interest rate. Usually a downward revision will force them to lower it (because they net they will be paying out = Rf - Rs). On the other hand, if Rf goes up and if one of the banks increases the Rs then other banks may be forced to do so too under competitive pressure. In some countries the central bank has the authority to revise Rs without revising the overnight lending rate. Term deposits with the bank (or certificates of deposit): Usually movements in these rates are more in sync with Rf than Rs is. The chief difference is that savings account offer more liquidity than term deposits and hence banks can offer lower rates and still get deposits under them --consider the higher interest rate offered by the term deposit as a liquidity risk premium. Generally, interest rates paid by instruments of similar risk profile that offer similar liquidity will move in parallel (otherwise there can be arbitrage). Sometimes these rates can move to anticipate a future change in Rf. Mortgage loan rates or other interests that you pay to the bank: If the risk free rate goes up, banks will increase these rates to keep the net interest they earn over risk free (= Δr = Rmort - Rf) the same. If Rf drops and if banks are not obliged to decrease loan rates then they will only do so if one of the banks does it first. P.S:- Wherever I have said they will do so when one of the banks does it first, I am not referring to a recursion but merely to the competitive market theory. Under such a theory, the first one to cut down the profit margin usually has a strong business incentive to do so (e.g., gain market share, or eliminate competition by lowering profit margins etc.). Others are forced to follow the trend.", "title": "" } ]
PLAIN-1870	pistachio principle	[ { "docid": "MED-4292", "text": "There is currently no single dietary or lifestyle intervention that is effective in long-term weight loss. Traditional weight loss diets tend to be low in total fat and therefore often restrict nut consumption. However, nuts are an important source of many vitamins, minerals, monounsaturated and polyunsaturated fatty acids. This paper reviewed all the available evidence from the literature in relation to nut consumption and body weight. The findings show that the role of nut consumption in body weight management is varied. Nuts, when included as part of an energy-controlled diet, were found in some instances to assist with weight loss. However, when nuts were added to an existing diet without controlling for energy intake, body weight increased, although to a lesser extent than theoretically predicted. There is limited evidence on the effect nut consumption has on type 2 diabetes, although available evidence indicates that nuts as part of a healthy diet do not cause weight gain and can have a positive influence on the fatty acid profile of a person with diabetes. This review shows there is a lack of evidence to support the restriction of nut consumption in weight management, indicating that further research is needed to assess the role of nuts in weight management.", "title": "A review of the evidence: nuts and body weight." }, { "docid": "MED-4286", "text": "Nuts are rich sources of multiple nutrients and phytochemicals associated with health benefits, including reduced cardiovascular disease risk. This has prompted recommendations to increase their consumption. However, they are also high in fat and are energy dense. The associations between these properties, positive energy balance and body weight raise questions about such recommendations. Numerous epidemiological and clinical studies show that nuts are not associated with weight gain. Mechanistic studies indicate this is largely attributable to the high satiety and low metabolizable energy (poor bioaccessibility leading to inefficient energy absorption) properties of nuts. Compensatory dietary responses account for 55-75% of the energy provided by nuts. Limited data suggest that routine nut consumption is associated with elevated resting energy expenditure and the thermogenic effect of feeding, resulting in dissipation of another portion of the energy they provide. Additionally, trials contrasting weight loss through regimens that include or exclude nuts indicate improved compliance and greater weight loss when nuts are permitted. Nuts may be included in the diet, in moderation, to enhance palatability, nutrient quality, and chronic disease risk reduction without compromising weight loss or maintenance.", "title": "Nuts and healthy body weight maintenance mechanisms." }, { "docid": "MED-4284", "text": "Peanuts and peanut butter are commonly consumed as a snack, meal component and ingredient in various commercial products. Their consumption is associated with reduced CVD risk and they pose little threat to positive energy balance. However, questions have arisen as to whether product form (e.g. whole nut v. butter) and processing properties (e.g. roasting and adding flavours) may compromise their positive health effects. The present study investigated the effects of peanut form and processing on two CVD risk factors: fasting plasma lipids and body weight. One hundred and eighteen adults (forty-seven males and seventy-one females; age 29.2 (sd 8.4) years; BMI 30.0 (sd 4.5) kg/m2) from Brazil, Ghana and the United States were randomised to consume 56 g of raw unsalted (n 23), roasted unsalted (n 24), roasted salted (n 23) or honey roasted (n 24) peanuts, or peanut butter (n 24) daily for 4 weeks. Peanut form and processing did not differentially affect body weight or fasting plasma lipid responses in the total sample. However, HDL-cholesterol increased significantly at the group level, and total cholesterol, LDL-cholesterol and TAG concentrations decreased significantly in individuals classified as having elevated fasting plasma lipids compared with those with normal fasting plasma lipids. These observations suggest that the processing attributes assessed in this trial do not compromise the lipid-lowering effects of peanuts, and do not negatively impact body weight. Further studies are warranted to determine the effects of form and processing on other health risk factors.", "title": "Effects of peanut processing on body weight and fasting plasma lipids." } ]	[ { "docid": "MED-3399", "text": "We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.", "title": "Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction." }, { "docid": "MED-2592", "text": "Background Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks. Results Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups. Conclusion Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.", "title": "Effects of pistachios on body weight in Chinese subjects with metabolic syndrome" }, { "docid": "MED-4710", "text": "OBJECTIVE: Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters, endothelial function, inflammation, and oxidation in healthy young men living in a controlled environment. METHODS: A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean age 22 y, range 21-24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements were performed at baseline and after each diet. RESULTS: Compared with the Mediterranean diet, the pistachio diet decreased glucose (P<0.001, -8.8+/-8.5%), low-density lipoprotein (P<0.001, -23.2+/-11.9%), total cholesterol (P<0.001, -21.2+/-9.9%), and triacylglycerol (P=0.008, -13.8+/-33.8%) significantly and high-density lipoprotein (P=0.069, -3.1+/-11.7%) non-significantly. Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly (P<0.001 for both). The pistachio diet significantly improved endothelium-dependent vasodilation (P=0.002, 30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and malondialdehyde and increased superoxide dismutase (P<0.001 for all), whereas there was no significant change in C-reactive protein and tumor necrosis factor-alpha levels. CONCLUSION: In this trial, we demonstrated that a pistachio diet improved blood glucose level, endothelial function, and some indices of inflammation and oxidative status in healthy young men. These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies. Copyright 2010. Published by Elsevier Inc.", "title": "Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study." }, { "docid": "MED-1726", "text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.", "title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles" }, { "docid": "MED-4295", "text": "Phytosterols were quantified in nuts and seeds commonly consumed in the United States. Total lipid extracts were subjected to acid hydrolysis and then alkaline saponfication, and free sterols were analyzed as trimethylsilyl derivatives by capillary GC-FID and GC-MS. Delta5-Avenasterol was quantified after alkaline saponification plus direct analysis of the glucoside. Sesame seed and wheat germ had the highest total phytosterol content (400-413 mg/100 g) and Brazil nuts the lowest (95 mg/100 g). Of the products typically consumed as snack foods, pistachio and sunflower kernel were richest in phytosterols (270-289 mg/100 g). beta-Sitosterol, Delta5-avenasterol, and campesterol were predominant. Campestanol ranged from 1.0 to 12.7 mg/100 g. Only 13 mg/100 g beta-sitosterol was found in pumpkin seed kernel, although total sterol content was high (265 mg/100 g). Phytosterol concentrations were greater than reported in existing food composition databases, probably due to the inclusion of steryl glycosides, which represent a significant portion of total sterols in nuts and seeds.", "title": "Phytosterol composition of nuts and seeds commonly consumed in the United States." }, { "docid": "MED-5137", "text": "Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences.", "title": "Black pepper and its pungent principle-piperine: a review of diverse physiological effects." }, { "docid": "MED-2521", "text": "A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibiotic-producing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 mug/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.", "title": "Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle." }, { "docid": "MED-2384", "text": "BACKGROUND: Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS: The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS: Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION: Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit. Copyright © 2013 National Lipid Association. All rights reserved.", "title": "Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects." }, { "docid": "MED-3274", "text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.", "title": "Olfactory detection of human bladder cancer by dogs: proof of principle study" }, { "docid": "MED-2997", "text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.", "title": "The Etiological Significance of Related Diseases" }, { "docid": "MED-4600", "text": "Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.", "title": "Essentials of Healthy Eating: A Guide" }, { "docid": "MED-2335", "text": "Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet.", "title": "Xenohormesis: health benefits from an eon of plant stress response evolution" }, { "docid": "MED-2606", "text": "Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.", "title": "Effect of turmeric on urinary mutagens in smokers." }, { "docid": "MED-3728", "text": "On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.", "title": "Strawberry fields forever?" }, { "docid": "MED-744", "text": "This paper presents a new interpretation of a unique Bronze Age (c. 3000-1100 BCE) Aegean wall painting in the building of Xeste 3 at Akrotiri,Thera. Crocus carturightianus and its active principle, saffron, are the primary subjects at Xeste 3. Several lines of evidence suggest that the meaning of these frescoes concerns saffron and healing: (1) the unusual degree of visual attention given to the crocus, including the variety of methods for display of the stigmas; (2) the painted depiction of the line of saffron production from plucking blooms to the collection of stigmas; and (3) the sheer number (ninety) of medical indications for which saffron has been used from the Bronze Age to the present. The Xeste 3 frescoes appear to portray a divinity of healing associated with her phytotherapy, saffron. Cultural and commercial interconnections between the Therans, the Aegean world, and their neighboring civilizations in the early 2nd millennium BCE indicate a close network of thematic exchange, but there is no evidence that Akrotiri borrowed any of these medicinal (or iconographic) representations. The complex production line, the monumental illustration of a goddess of medicine with her saffron attribute, and this earliest botanically accurate image of an herbal medication are all Theran innovations.", "title": "Therapy with saffron and the goddess at Thera." }, { "docid": "MED-1578", "text": "Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.", "title": "Dietary clues to the pathogenesis of Crohn's disease." }, { "docid": "MED-3607", "text": "The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.", "title": "Radioprotection by plant products: present status and future prospects." }, { "docid": "MED-3887", "text": "Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.", "title": "Food Animals and Antimicrobials: Impacts on Human Health" }, { "docid": "MED-1439", "text": "BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.", "title": "Brain volume changes on longitudinal magnetic resonance imaging in normal older people." }, { "docid": "MED-1878", "text": "Excerpt Second in a series of publications from the Institute of Medicine's Quality of Health Care in America project Today's health care providers have more research findings and more technology available to them than ever before. Yet recent reports have raised serious doubts about the quality of health care in America. Crossing the Quality Chasm makes an urgent call for fundamental change to close the quality gap. This book recommends a sweeping redesign of the American health care system and provides overarching principles for specific direction for policymakers, health care leaders, clinicians, regulators, purchasers, and others. In this comprehensive volume the committee offers: A set of performance expectations for the 21st century health care system. A set of 10 new rules to guide patient-clinician relationships. A suggested organizing framework to better align the incentives inherent in payment and accountability with improvements in quality. Key steps to promote evidence-based practice and strengthen clinical information systems. Analyzing health care organizations as complex systems, Crossing the Quality Chasm also documents the causes of the quality gap, identifies current practices that impede quality care, and explores how systems approaches can be used to implement change. Copyright 2001 by the National Academy of Sciences. All rights reserved.", "title": "Crossing the Quality Chasm: A New Health System for the 21st Century" }, { "docid": "MED-3292", "text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.", "title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G" }, { "docid": "MED-3309", "text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.", "title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G" }, { "docid": "MED-4602", "text": "The strategy of \"manufacturing uncertainty\" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called \"product defense\" or \"litigation support.\" As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.", "title": "Manufactured uncertainty: protecting public health in the age of contested science and product defense." }, { "docid": "MED-5115", "text": "The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus \"high\" doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of \"the dose defines the poison\" applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.", "title": "Genistein genotoxicity: critical considerations of in vitro exposure dose." }, { "docid": "MED-1951", "text": "Late preterm (LP) birth (34 0/7 - 36 6/7 weeks' gestation) accounts for nearly three-fourths of all preterm births, making this population a sizeable public health concern. The immature fetal development associated with LP delivery increases the risk of mortality and short-term medical complications. Which combination of maternal, fetal, or neonatal risk factors may be most critical has only recently begun to be addressed, and whether LP birth's disruptive impact on brain development will exert adverse effects on neuropsychological functioning in childhood and adolescence has been understudied. Early data have shown a graded response, with LP children often functioning better than very preterm children but worse than term children, and with subtle intellectual and neuropsychological deficits in LP children compared with healthy children born at term gestational age. Further characterization of the neuropsychological profile is required and would be best accomplished through prospective longitudinal studies. Moreover, since moderate and LP births result in disparate medical and psychological outcomes, the common methodology of combining these participants into a single research cohort to assess risk and outcome should be reconsidered. The rapidly growing LP outcomes literature reinforces a critical principle: fetal development occurs along a dynamic maturational continuum from conception to birth, with each successive gestational day likely to improve overall outcome.", "title": "Late preterm birth: a review of medical and neuropsychological childhood outcomes." }, { "docid": "MED-2810", "text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".", "title": "Curcumin as \"Curecumin\": from kitchen to clinic." }, { "docid": "MED-2811", "text": "Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.", "title": "Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations." }, { "docid": "MED-2824", "text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.", "title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution." }, { "docid": "MED-4394", "text": "Acne vulgaris, the most common skin disease of western civilization, has evolved to an epidemic affecting more than 85% of adolescents. Acne can be regarded as an indicator disease of exaggerated insulinotropic western nutrition. Especially milk and whey protein-based products contribute to elevations of postprandial insulin and basal insulin-like growth factor-I (IGF-I) plasma levels. It is the evolutional principle of mammalian milk to promote growth and support anabolic conditions for the neonate during the nursing period. Whey proteins are most potent inducers of glucose-dependent insulinotropic polypeptide secreted by enteroendocrine K cells which in concert with hydrolyzed whey protein-derived essential amino acids stimulate insulin secretion of pancreatic β-cells. Increased insulin/IGF-I signaling activates the phosphoinositide-3 kinase/Akt pathway, thereby reducing the nuclear content of the transcription factor FoxO1, the key nutrigenomic regulator of acne target genes. Nuclear FoxO1 deficiency has been linked to all major factors of acne pathogenesis, i.e. androgen receptor transactivation, comedogenesis, increased sebaceous lipogenesis, and follicular inflammation. The elimination of the whey protein-based insulinotropic mechanisms of milk will be the most important future challenge for nutrition research. Both, restriction of milk consumption or generation of less insulinotropic milk will have an enormous impact on the prevention of epidemic western diseases like obesity, diabetes mellitus, cancer, neurodegenerative diseases and acne. Copyright © 2011 S. Karger AG, Basel.", "title": "Evidence for acne-promoting effects of milk and other insulinotropic dairy products." }, { "docid": "MED-5059", "text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives: branching glycosyltransferase from Rhodothermus obamensis expressed in Bacillus subtilis, cassia gum, cyclamic acid and its salts (dietary exposure assessment), cyclotetraglucose and cyclotetraglucose syrup, ferrous ammonium phosphate, glycerol ester of gum rosin, glycerol ester of tall oil rosin, lycopene from all sources, lycopene extract from tomato, mineral oil (low and medium viscosity) class II and class III, octenyl succinic acid modified gum arabic, sodium hydrogen sulfate and sucrose oligoesters type I and type II. Specifications for the following food additives were revised: diacetyltartaric acid and fatty acid esters of glycerol, ethyl lauroyl arginate, glycerol ester of wood rosin, nisin preparation, nitrous oxide, pectins, starch sodium octenyl succinate, tannic acid, titanium dioxide and triethyl citrate. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.", "title": "Evaluation of certain food additives. Seventy-first report of the Joint FAO/WHO Expert Committee on Food Additives." } ]
941	Why do sole proprietors in India generally use a current account?	[ { "docid": "456636", "text": "Current account offers a lot of benefits for sole proprietors. Think of it like bank account for a company. The bank provides a host of facilities for the company. A sole proprietor does not have enough value as that of a company for a bank but needs similar services. Thus Indian banks offer a toned down version of the account offered to a company. Current account offer very good overdraft ( withdrawing money even if balance is zero). This feature is very useful as business cycles and payment schedules can be different for each supplier/customer the sole proprietor does business with. Imagine the sole proprietor account has balance of zero on day 0. customer X made payment by cheque on day 1. Cheques will get credited only on Day 3 (Assume Day 2 is a national holiday or weekend). Sole proprietor gave a cheque to his supplier on day 0. The supplier deposited the cheque on Day 0 and the sole proprietor's bank will debit the the proprietor's account on day 1. As customer's cheque will get credited only day 3, the overdraft facility will let the proprietor borrow from the bank Interestingly, current accounts were offered long before Indian banks started offering customized accounts to corporate customers. The payment schedule mentioned in my example is based on a clearing system > 10 years ago. Systems have become much simpler now but banks have always managed to offer something significantly extra on lines similar to my example above to proprietor over a savings bank account", "title": "" }, { "docid": "295203", "text": "No. Current account is not a requirement. You can use savings account. You would need to pay taxes on interest. Savings account have limitation on number of withdrawal in a quarter, hence most sole proprietorship have current account.", "title": "" } ]	[ { "docid": "109203", "text": "You could, but the bank won't let you... If you're a sole proprietor - then you could probably open a personal account and just use it, and never tell them that is actually a business. However, depending on your volume of operations, they may switch you on their own to business account by the pattern of your transactions. For corporations, you cannot use a personal account since the corporation is a separate legal entity that owns the funds. Also, you're generally required to separate corporate and personal funds to keep the limited liability protection (which is why you have the corporation to begin with). Generally, business accounts have much higher volumes and much more transactions than personal accounts, and it costs more for the banks to run them. In the US, some banks offer free, or very low-cost, business accounts for small businesses that don't need too many transactions. I'm sure if you shop around, you'll find those in Canada as well.", "title": "" }, { "docid": "377152", "text": "\"According to IRS Publication 1635, Understanding your EIN (PDF), under \"\"What is an EIN?\"\" on page 2: Caution: An EIN is for use in connection with your business activities only. Do not use your EIN in place of your social security number (SSN). As you say your EIN is for your business as a sole proprietor, I would also refer to Publication 334, Tax Guide for Small Business, under \"\"Identification Numbers\"\": Social security number (SSN). Generally, use your SSN as your taxpayer identification number. You must put this number on each of your individual income tax forms, such as Form 1040 and its schedules. Employer identification number (EIN). You must also have an EIN to use as a taxpayer identification number if you do either of the following. Pay wages to one or more employees. File pension or excise tax returns. If you must have an EIN, include it along with your SSN on your Schedule C or C-EZ as instructed. While I can't point to anything specifically about bank accounts, in general the guidance I see is that your SSN is used for your personal stuff, and you have an EIN for use in your business where needed. You may be able to open a bank account listing the EIN as the taxpayer identification number on the account. I don't believe there's a legal distinction between what makes something a \"\"business\"\" account or not, though a bank may have different account offerings for different purposes, and only offer some of them to entities rather than individuals. If you want to have a separate account for your business transactions, you may want them to open it in the name of your business and they may allow you to use your EIN on it. Whether you can do this for one of their \"\"personal\"\" account offerings would be up to the bank. I don't see any particular advantages to using your EIN on a bank account for an individual, though, and I could see it causing a bit of confusion with the bank if you're trying to do so in a way that isn't one of their \"\"normal\"\" account types for a business. As a sole proprietor, there really isn't any distinction between you and your business. Any interest income is taxable to you in the same way. But I don't think there's anything stopping you legally other than perhaps your particular bank's policy on such things. I would suggest contacting your bank (or trying several banks) to get more information on what account offerings they have available and what would best fit you and your business's needs.\"", "title": "" }, { "docid": "179066", "text": "\"Your own site/business. I’m in freelancing and internet business for 15 years, 20 years IT experience. Currently i use freelance websites for cheap Asian employees, very seldom for EU/USA employees, and if only if local competition is heavily out-pricing qualified staff. Till I went \"\"limited\"\" i.e., founded a limited corporation I was jobbing as freelancer and sole proprietor, both with limited success due to the strong Asian competition i myself currently hire. The point where freelancing got \"\"not sustainable\"\" as primary income was 2006 for me, don’t want to get into detail but every freelancer who was active back then knows what I mean, it was like whole India got internet. If you have absolutely no references, do it for the references a limited time and see the fee you pay as service for you to get references, then start your own web identity, either as freelancer or as corporation. Make sure you take your very satisfied customers with you. Every \"\"very satisfied\"\" customer in your contact list means 10 new customers which mean 2 new customers which mean 0.2 new customers and so on. Honestly, this info is solely based on experience of this niche fro ma European citizen perspective, if you’re based anywhere else the situation might be totally different.\"", "title": "" }, { "docid": "506108", "text": "\"LLC is, as far as I know, just a US thing, so I'm assuming that you are in the USA. Update for clarification: other countries do have similar concepts, but I'm not aware of any country that uses the term LLC, nor any other country that uses the single-member LLC that is disregarded for income tax purposes that I'm referring to here (and that I assume the recruiter also was talking about). Further, LLCs vary by state. I only have experience with California, so some things may not apply the same way elsewhere. Also, if you are located in one state but the client is elsewhere, things can get more complex. First, let's get one thing out of the way: do you want to be a contractor, or an employee? Both have advantage, and especially in the higher-income areas, contractor can be more beneficial for you. Make sure that if you are a contractor, your rate must be considerably higher than as employee, to make up for the benefits you give up, as well as the FICA taxes and your expense of maintaining an LLC (in California, it costs at least $800/year, plus legal advice, accounting, and various other fees etc.). On the other hand, oftentimes, the benefits as an employee aren't actually worth all that much when you are in high income brackets. Do pay attention to health insurance - that may be a valuable benefit, or it may have such high deductibles that you would be better off getting your own or paying the penalty for going uninsured. Instead of a 401(k), you can set up an IRA (update or various other options), and you can also replace all the other benefits. If you decide that being an employee is the way to go, stop here. If you decide that being a contractor is a better deal for you, then it is indeed a good idea to set up an LLC. You actually have three fundamental options: work as an individual (the legal term is \"\"sole proprietorship\"\"), form a single-member LLC disregarded for income tax purposes, or various other forms of incorporation. Of these, I would argue that the single-member LLC combines the best of both worlds: taxation is almost the same as for sole proprietorship, the paperwork is minimal (a lot less than any other form of incorporation), but it provides many of the main benefits of incorporating. There are several advantages. First, as others have already pointed out, the IRS and Department of Labor scrutinize contractor relationships carefully, because of companies that abused this status on a massive scale (Uber and now-defunct Homejoy, for instance, but also FedEx and other old-economy companies). One of the 20 criteria they use is whether you are incorporated or not. Basically, it adds to your legal credibility as a contractor. Another benefit is legal protection. If your client (or somebody else) sues \"\"you\"\", they can usually only sue the legal entity they are doing business with. Which is the LLC. Your personal assets are safe from judgments. That's why Donald Trump is still a billionaire despite his famous four bankruptcies (which I believe were corporate, not personal, bankrupcies). Update for clarification Some people argue that you are still liable for your personal actions. You should consult with a lawyer about the details, but most business liabilities don't arise from such acts. Another commenter suggested an E&O policy - a very good idea, but not a substitute for an LLC. An LLC does require some minimal paperwork - you need to set up a separate bank account, and you will need a professional accounting system (not an Excel spreadsheet). But if you are a single member LLC, the paperwork is really not a huge deal - you don't need to file a separate federal tax return. Your income will be treated as if it was personal income (the technical term is that the LLC is disregarded for IRS tax purposes). California still does require a separate tax return, but that's only two pages or so, and unless you make a large amount, the tax is always $800. That small amount of paperwork is probably why your recruiter recommended the LLC, rather than other forms of incorporation. So if you want to be a contractor, then it sounds like your recruiter gave you good advice. If you want to be an employee, don't do it. A couple more points, not directly related to the question, but hopefully generally helpful: If you are a contractor (whether as sole proprietor or through an LLC), in most cities you need a business license. Not only that, but you may even need a separate business license in every city you do business (for instance, in the city where your client is located, even if you don't live there). Business licenses can range from \"\"not needed\"\" to a few dollars to a few hundred dollars. In some cities, the business license fee may also depend on your income. And finally, one interesting drawback of a disregarded LLC vs. sole proprietorship as a contractor has to do with the W-9 form and your Social Security Number. Generally, when you work for somebody and receive more than $600/year, they need to ask you for your Social Security Number, using form W-9. That is always a bit of a concern because of identity theft. The IRS also recognizes a second number, the EIN (Employer Identification Number). This is basically like an SSN for corporations. You can also apply for one if you are a sole proprietor. This is a HUGE benefit because you can use the EIN in place of your SSN on the W-9. Instant identity theft protection. HOWEVER, if you have a disregarded LLC, the IRS says that you MUST use your SSN; you cannot use your EIN! Update: The source for that information is the W-9 instructions; it specifically only excludes LLCs.\"", "title": "" }, { "docid": "100764", "text": "\"You don't specify which country you are in, so my answers are more from a best practice view than a legal view.. I don't intend on using it for personal use, but I mean it's just as possible. This is a dangerous proposition.. You shouldn't co-mingle business expenses with personal expenses. If there is a chance this will happen, then stop, make it so that it won't happen. The big danger is in being able to have traceability between what you are doing for the business, and what you are doing for yourself. If you are using this as a \"\"staging\"\" account for investments, etc., are those investments for yourself? Or for the business? Is tax treatment on capital gains and/or dividends the same for personal and business in your jurisdiction? If you buy a widget, is the widget an expense against business income? Or is it an out of pocket expense for personal consumption? The former reduces your taxable income, the latter does not. I don't see the benefit of a real business account because those have features specific to maybe corporations, LLC, and etc. -- nothing beneficial to a sole proprietor who has no reports/employees. The real benefit is that there is a clear delineation between business income/expenses and personal income/expenses. This account can also accept money and hold it from business transactions/sales, and possibly transfer some to the personal account if there's no need for reinvesting said amount/percentage. What you are looking for is a commonly called a current account, because it is used for current expenses. If you are moving money out of the account to your personal account, that speaks to paying yourself, which has other implications as well. The safest/cleanest way to do this is to: While this may sound like overkill, it is the only way to guarantee that income/expenses are allocated to the correct entity (i.e. you, or your business). From a Canadian standpoint:\"", "title": "" }, { "docid": "418647", "text": "Do you need to incorporate? This depends on whether the company prefers you to be incorporated. If you are going through a recruiting company, some of them are willing to deal with non-incorporated people (Sole Proprietor) and withhold taxes from your cheques for you. If you do want to incorporate, you can do it yourself, go through a paralegal, or you can even do it online. I did mine in Ontario for about $300 (no name search - i just have a numbered corporation like 123456 Ontario Inc.) through www.oncorp.com - there are other sites that do it as well. Things to consider - if you're contracting through a corporation you most likely need to: Talk to an accountant about these for clarification - most of them will give you an initial consultation for free. Generally speaking, accountant fees for corporate filing taxes averages about $1000-2000 a year.", "title": "" }, { "docid": "513051", "text": "\"Interesting as I am in the exact same situations as yourself. I, in fact, just incorporated. You will be able \"\"save\"\" more in taxes in the end. The reason I put \"\"save\"\" in quotes, is that you don't necessarily save on taxes, but you can defer taxes. The driving factor behind this is that you specify your own fiscal calendar/year. Incorporating allows you to defer income for up to 6 months. Meaning that if you make your fiscal year starting in August or September, for example, you can claim that income on the following year (August + 6 months = February). It allows you to keep the current year taxes down. Also, any income left over at year end, is taxed at 15% (the Corporation rate) rather than the 30-40% personal rate you get with a sole-proprietorship. In a nutshell, with sole-proprietorship, all income is taxable (after write-offs)... in a corporation, you can take some of that income and keep it in the corporation (gives your company a \"\"value\"\"), and is only taxed at 15% - big saving there. I primarily work with US businesses. I am, however, a dual-citizen, US and Canadian, which allowed me as a sole-proprietor, to easily work with US companies. However, as a sole-proprietor or a Corporation, you simply need to get an EIN from the IRS and any US company will report earnings to that number, with no deductions. At year end, it is your responsibility to file the necessary tax forms and pay the necessary taxes to both countries. Therefore you can solicit new US business if you choose, but this is not restricted to corporations. The real benefit in incorporating is what I mentioned above. My suggestion to you is to speak with you CA, who can outline all benefits. Revenue Canada's website had some good information on this topic as well. Please let me know if you need anything else explained.\"", "title": "" }, { "docid": "1873", "text": "\"I expect the company wanted to pay you for a product (on a purchase order) rather than as a contract laborer. Whatever. Would they be willing to re-issue the check to you as a sole proprietor of a business named ABC Consulting (or anything like that)? You can register your sole proprietor business with the state using a \"\"Doing Business As\"\" (DBA, or fictitious name), and then open the bank account for your business using the check provided by the customer as the first deposit. (There is likely a smaller registration fee for the DBA.) If they won't re-issue the check and you have to go the LLC route... Scrounge up $125 doing odd jobs or borrowing from a friend or parents. Seriously, anyone can earn that amount of money in a week or two. Besides the filing fee for the LLC, your bank may require you to provide an Operating Agreement (which is not required by the State). The Operating Agreement can be simple, or more complex if you have a partner (even if it's a spouse). If you do have a partner, it is essential to have such an agreement because it would specify the responsibilities and benefits allocated to each partner, particularly in the event of equity distributions (taking money out of the business, or liquidating and ending the LLC). There are websites that will provide you a boilerplate form for Operating Agreements. But if your business is anything more than just single member LLC, you should pay an attorney to draw one up for you so the wording is right. It's a safeguard against potential future lawsuits. And, while we're at it, don't forget to obtain a EIN (equivalent to a SSN) from the IRS for your LLC. There's no cost, but you'll have to have it to file taxes as a business for every year the LLC exists and has income. Good luck!\"", "title": "" }, { "docid": "523564", "text": "\"While she can certainly get an LLC or EIN, it isn't necessarily required or needed. She can file as a sole-proprietor on her (or your joint) taxes by filling out a schedule-C addition to the 1040. Any income or losses will pass through to your existing income situation (from W-2's and such). The general requirement for filing as a business in this regard has nothing to do with any minimum income, revenue, or size. It is simply the intent to treat it as a business, and unlike a hobby, the overall intent to earn a profit eventually. If you're currently reporting the 1099-MISC income, but not deducting the expenses, this would be a means for you to offset the income with the expenses you mentioned (and possibly other legitimate ones). There is no \"\"2% AGI\"\" restriction for schedule-C.\"", "title": "" }, { "docid": "202570", "text": "I think you are asking quite a few questions here; If you have Rs 10000, its better you get it converted in India before you leave. Most Banks and Exchange houses like Western Union would take Rupees and Give you USD. What do they do with USD, there are other who give them USD and need Rupees. They make a spread in this process. If you are getting a salary in USD in US, whenever you want to transfer money to India, the Banks or Remittance services like Western Union would take USD from your US Account and Transfter equivalent Money into your Bank Account in India in Rupees. They will tell the exchange rate applicable. Depending on why visa type & the duration you are going, your company should be able to tell you your tax liabilities in the US. Read similar questions here to get a general idea.", "title": "" }, { "docid": "590310", "text": "Alright, team! I found answers to part 1) and part 2) that I've quote below, but still need help with 3). The facts in the article below seem to point to the ability for the LLC to contribute profit sharing of up to 25% of the wages it paid SE tax on. What part of the SE tax is that? I assume the spirit of the law is to only allow the 25% on the taxable portion of the income, but given that I would have crossed the SS portion of SE tax, I am not 100%. (From http://www.sensefinancial.com/services/solo401k/solo-401k-contribution/) Sole Proprietorship Employee Deferral The owner of a sole proprietorship who is under the age of 50 may make employee deferral contributions of as much as $17,500 to a Solo 401(k) plan for 2013 (Those 50 and older can tack on a $5,500 annual catch-up contribution, bringing their annual deferral contribution to as much as $23,000). Solo 401k contribution deadline rules dictate that plan participant must formally elect to make an employee deferral contribution by Dec. 31. However, the actual contribution can be made up until the tax-filing deadline. Pretax and/or after-tax (Roth) funds can be used to make employee deferral contributions. Profit Sharing Contribution A sole proprietorship may make annual profit-sharing contributions to a Solo 401(k) plan on behalf of the business owner and spouse. Internal Revenue Code Section 401(a)(3) states that employer contributions are limited to 25 percent of the business entity’s income subject to self-employment tax. Schedule C sole-proprietors must base their maximum contribution on earned income, an additional calculation that lowers their maximum contribution to 20 percent of earned income. IRS Publication 560 contains a step-by-step worksheet for this calculation. In general, compensation can be defined as your net earnings from self-employment activity. This definition takes into account the following eligible tax deductions: (1) the deduction for half of self-employment tax and (2) the deduction for contributions on your behalf to the Solo 401(k) plan. A business entity’s Solo 401(k) contributions for profit sharing component must be made by its tax-filing deadline. Single Member LLC Employee Deferral The owner of a single member LLC who is under the age of 50 may make employee deferral contributions of as much as $17,500 to a Solo 401(k) plan for 2013 (Those 50 and older can tack on a $5,500 annual catch-up contribution, bringing their annual deferral contribution to as much as $23,000). Solo 401k contribution deadline rules dictate that plan participant must formally elect to make an employee deferral contribution by Dec. 31. However, the actual contribution can be made up until the tax-filing deadline. Pretax and/or after-tax (Roth) funds can be used to make employee deferral contributions. Profit Sharing Contribution A single member LLC business may make annual profit-sharing contributions to a Solo 401(k) plan on behalf of the business owner and spouse. Internal Revenue Code Section 401(a)(3) states that employer contributions are limited to 25 percent of the business entity’s income subject to self-employment tax. Schedule C sole-proprietors must base their maximum contribution on earned income, an additional calculation that lowers their maximum contribution to 20 percent of earned income. IRS Publication 560 contains a step-by-step worksheet for this calculation. In general, compensation can be defined as your net earnings from self-employment activity. This definition takes into account the following eligible tax deductions: (i) the deduction for half of self-employment tax and (ii) the deduction for contributions on your behalf to the Solo 401(k). A single member LLC’s Solo 401(k) contributions for profit sharing component must be made by its tax-filing deadline.", "title": "" }, { "docid": "448981", "text": "am I allowed to transfer into NRE account from paypal? Credits into NRE accounts are restricted. It has to be established that the funds being credited are income outside of India. In case of paypal, paypal uses local clearing to credit funds into Bank Accounts. So essentially one cannot credit NRE account by domestic clearing network like NEFT. It is best that you withdraw the funds into Bank Account outside India and use SWIFT or remittance service to credit your NRE account. I do not want to transfer to an NRO account since the money credited into it will become taxable. This is not the right assumption. Credits into NRO are not taxable by default; if you establish that the funds are from outside India, there is no tax on the income money transferred from abroad into the NRO account. However, the interest that will be paid by the bank on the balance of the NRO account is taxable income in India and is subject to TDS. In contrast, interest paid on the balance in an NRE account is not taxable in India and is not subject to TDS as long as you maintain NRI status. However it does make sense to keep accounts segregated, i.e. income generated in India, credit the NRO account and income generated outside India credit to NRE.", "title": "" }, { "docid": "418884", "text": "Book keeping as a sole proprietor will seem like a headache. Basically you have to have two accounts for everything and track specifics for any company assets that are mixed use (such as mileages). No real downsides aside from that. We just bought a start up kit and then modified it an then did a lot of research on proper registrations. I found out later you can have a legal expert do it for like 250-300. If we had known that it would have been worth it. The state and fed registration is a boring headache. Your time is better spent earning.", "title": "" }, { "docid": "483942", "text": "This depends on the state law. In case of the State of New York - these are the criteria for sourcing the NY income: As a sole proprietor or partnership, your New York source income includes: Business activities As a nonresident sole proprietor or partnership, you carry on a business, trade, profession, or occupation within New York State if you (or your business): As you can see, the qualification depends on the way you do business, and the amount of business transactions you have in New York. If it is not clear to you - talk to a CPA/EA licensed to practice in the State of New York to give you an advice.", "title": "" }, { "docid": "58611", "text": "Can I still use the old EIN from partnership times for the new sole proprietorship? Or should I apply for a new EIN? You cannot use the same EIN. Unless you have employees, you should use your SSN for the sole proprietorship. If you have employees - you should get a new EIN (if you don't have one already for yourself as a sole proprietor - you can only have one). Can I actually start to use my SSN in this situation for the sole proprietorship? In this particular case, not only you can - you should.", "title": "" }, { "docid": "365456", "text": "There are quite a few questions as to how you are recording your income and expenses. If you are running the bakery as a Sole Proprietor, with all the income and expense in a business account; then things are easy. You just have to pay tax on the profit [as per the standard tax bracket]. If you running it as individual, you are still only liable to pay tax on profit and not turnover, however you need to keep a proper book of accounts showing income and expense. Get a Accountant to do this for you there are some thing your can claim as expense, some you can't.", "title": "" }, { "docid": "390368", "text": "As a sole proprietor, the tax liability of your business is calculated based on combining your business income with your personal income together. It is good advice to keep all personal and business financial matters separate. This makes it easier to prove to the IRS that all your business expenses are actually business related. In this case however, the two items [tax payment for personal income vs tax payment for business income] are inseparable. What you can do, however, for your own personal records, is calculate how much of your tax payment relates to your business. I wouldn't get complicated about this; I would simply take the net income of your business as a % of your taxable income, and multiply that against your tax payment. ie: if your business net income is $10,000, and your total taxable income is $50,000, and you paid $6,000 in taxes, I would record that 20% of the $6k was related to business income. If you have a separate bank account for your sole proprietorship, you could make a transfer to your personal account of $1,200, and then make the $6k payment from your personal account. Remember that tax payments for either your sole proprietorship and your personal income will be treated the same: federal tax payments are not tax deductible, and state tax payments are tax deductible, whether they were paid for your sole proprietorship or the rest of your personal income. So even though this method is simplistic [for example, it doesn't factor in that different investment income types earned personally will have a lower rate than your sole proprietorship income], any difference wouldn't have an impact on any future tax liability. This would only be for your own personal record keeping.", "title": "" }, { "docid": "367754", "text": "I feel the need to separate my freelance accounts from my personal accounts. Yes, you should. Should I start another savings account or a current account? Do you need the money for daily spending? Do you need to re-invest in your business? Use a current account. If you don't need the money for business expenses, put it away in your savings account or even consider term deposits. Don't rule out a hybrid approach either (some in savings account, some in current account). What criteria should I keep in mind while choosing a bank? (I thought of SBI since it has a lot of branches and ATMs). If you are involved in online banking and that is sufficient for most of your needs, bank and ATM locations shouldn't matter all that much. If you are saving a good chunk of money, you want to at least have that keep up with inflation. Research bank term deposit interest rates. The tend to be higher than just having your money sit in a savings account. Again, it depends on how and when you expect to need the money. What do I keep in mind while paying myself? Paying yourself could have tax implications. This depends on how are set up to freelance. Are you a business entity or are you an individual? You should look in to the following in India: The other thing to consider is rewarding yourself for the good work done. Pay yourself a reasonable amount. If you decide to expand and hire people going forward, you will have a better sense of business expenses involved when paying salaries. Tips on managing money in the business account. This is a very generic question. I can only provide a generic response. Know how much you are earning and how much your are putting back in to the business. Be reasonable in how much you pay yourself and do the proper research and paperwork from a taxation point of view.", "title": "" }, { "docid": "234510", "text": "\"TL;DR: Get a tax adviser (EA/CPA licensed in your State) for tax issues, and a lawyer for the Operating Agreement, labor law and contract related issues. Some things are not suitable for DIY unless you know exactly what you're doing. We both do freelance work currently just through our personal names. What kind of taxes are we looking into paying into the business (besides setup of everything) compared to being a self proprietor? (I'm seeing that the general answer is no, as long as income is <200k, but not certain). Unless you decide to have your LLC taxed as a corporation, there's no change in taxes. LLC, by default, is a pass-through entity and all income will flow to your respective tax returns. From tax perspective, the LLC will be treated as a partnership. It will file form 1065 to report its income, and allocate the income to the members/partners on schedules K-1 which will be given to you. You'll use the numbers on the K-1 to transfer income allocated to you to your tax returns and pay taxes on that. Being out of state, will she incur more taxes from the money being now filtered through the business? Your employee couldn't care less about your tax problems. She will continue receiving the same salary whether you are a sole proprietor or a LLC, or Corporatoin. What kind of forms are we looking into needing/providing when switching to a LLC from freelance work? Normally we just get 1099's, what would that be now? Your contract counterparts couldn't care less about your tax problems. Unless you are a corporation, people who pay you more than $600 a year must file a 1099. Since you'll be a partnership, you'll need to provide the partnership EIN instead of your own SSN, but that's the only difference. Are LLC's required to pay taxes 4 times per year? We would definitely get an accountant for things, but being as this is side work, there will be times where we choose to not take on clients, which could cause multiple months of no income. Obviously we would save for when we need to pay taxes, but is there a magic number that says \"\"you must now pay four times per year\"\". Unless you choose to tax your LLC as a corporation, LLC will pay no taxes. You will need to make sure you have enough withholding to cover for the additional income, or pay the quarterly estimates. The magic number is $1000. If your withholding+estimates is $1000 less than what your tax liability is, you'll be penalized, unless the total withholding+estimates is more than 100% of your prior year tax liability (or 110%, depending on the amounts). The LLC would be 50% 50%, but that work would not always be that. We will be taking on smaller project through the company, so there will be times where one of us could potentially be making more money. Are we setting ourselves up for disaster if one is payed more than the other while still having equal ownership? Partnerships can be very flexible, and equity split doesn't have to be the same as income, loss or assets split. But, you'll need to have a lawyer draft your operational agreement which will define all these splits and who gets how much in what case. Make sure to cover as much as possible in that agreement in order to avoid problems later.\"", "title": "" }, { "docid": "570639", "text": "\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"", "title": "" }, { "docid": "344290", "text": "foreign income, transfer it to my savings account in India Yes you can transfer to India. The right account would be NRO/NRE. As an NRI one should not hold a regular savings account. forum that foreign income is not taxable unless used to buy stocks, fds etc If you are an NRI, income earned outside of India is not taxable in India. However any income you generate in India is taxable, i.e. interest income, gains from shares etc. Do we need to pay taxes for the money transferred No tax if you are an NRI even if you transfer funds to India. Taxation does not depend on whether or not you transfer the money, it depends on your status used to pay home EMIs or principle amount? You can use the money for what ever you like.", "title": "" }, { "docid": "314339", "text": "\"So it seems like a lot of people here aren't exactly sure about why this works and its financial implications. So what you are referring to is in Finance something called Funds Transfer Pricing or FTP (often referred to as just Transfer Pricing). Like anything else, FTP has its place. Most companies; however, don't use it properly. FTP, theoretically, has one primary purpose (although it's developed a second): to properly allocate opportunity costs across divisions. Let's say Company A produces widgets. They sell these widgets for $200 at a TOTAL COST of $150 and book profits of $50. Now to produce the widget Division 1 makes a computer chip at a cost of $50 that it then \"\"sells\"\" to Division 2 for $60. Division 1 then books a profit of $10. Division 2 then makes some plastic stuff and assembles the device. This is labor intensive so Division 2's costs are $100. Company A sells the completed device for $150. Division 2 subsequently books profits of $40, and appears much more profitable than Division 1, on the surface. The problem arises when Division 1 could sell the chip to the open market for $125. Now it costs them $50 to produce, and they could make a theoretical profit of $75. This is MORE than the company makes AS A WHOLE on the entire device. By having Division 2 pay effectively \"\"fair market price\"\" for that chip, you realize that Division 2 is really operating at a loss (the opportunity cost of not selling the chip to market is greater than producing the completed device). Company A would be better off getting rid of Division 2 and solely focusing on Division 1. In a good FTP system, Division 2 would pay the fair market price of $125. If done properly, management would hopefully realize it should divest Division 2. That's the *fundamental premise* behind FTP. In actuality things get much more complicated because of economics, the company itself, branding, IT, operations, management, PPE, labor laws, etc. Thats why most companies screw it up. All that other stuff falls under whats called cost allocation accounting. It gets VERY complex and entire masters courses are dedicated to it (different methods, etc.) The other thing you can do with FTP is get crazy tax breaks due to various tax laws. The simplified explanation is that divisions pay taxes on profits to the government *that division* is located in (this works on the state level, too btw.). GE does a lot of this and it's a big part of why they pay almost no-taxes. Again, it gets more complicated when you involve audits as there's some grey area legally. For simplicity, assume tax rates are 40% in the US and 10% in India. So let's say GE makes an airplane engine in the US but \"\"finishes\"\" manufacturing in India. These specific engines costs $5,000,000 for the US division to make, up to a certain point. The US division can then sell the engine at a break even to India. So India \"\"pays\"\" $5,000,000 for the engine. The US division then books no profit. India finishes the manufacturing with additional costs of $1,000,000. The India division then sells the engine to the open market for $9,000,000 . Therefore, the India division books a profit of $3,000,000 and pays taxes of $300,000. Now GE as a whole makes a profit of $3,000,000 less taxes of $300,000 = net profit of $2,700,00. Further, let's say the fair market value of the engine, as is, when the US sells to India is $7,000,000. That would mean US *should* book profits of $2,000,000 and India *should* book profits of $1,000,000. Total taxes by GE are now $800,000 (US) + $100,000 (India) = $900,000. However, what's important is that NET PROFIT is now $2,100,000. *GE just saved $600,000 in taxes by doing this. The beauty of this is, divisions are supposed to charge fair market value for products FTP'd internationally; however, it's REALLY hard for the IRS to say what the value of an unfinished product really is (heck, you could be offering bulk discounts, etc.)... The fact is, often, US divisions have skilled labor that is difficult to replicate elsewhere. They just show US divisions operating at losses to make the company as a whole better. The problem, again, arises when top management don't fully appreciate or understand the reasoning behind this stuff. They end up making cuts to US labor because it's \"\"unprofitable\"\" without thinking about the entire story. I know this is very long winded but hope it helps! tldr; companies FTP to recognizes profitability and opportunity costs of divisions as well as use it for overseas tax breaks.* Side note: Politically speaking, people who know how this works are pissed off about it in the U.S. (don't worry though, most politicians on both sides don't have a clue). We have high corporate tax rates relative to other countries and IRS loopholes allow this kind of thing (lobbying $$). It's also why, economically, you can't just raise *corporate* tax rates to increase domestic tax reciepts as more companies will just implement this process (it's complicated to do properly). Also, please don't say 50 years ago tax rates were higher and raising taxes increased receipts. The fact is most companies couldn't even FATHOM doing this 50 years ago, no less even 20. edit: some clarification in wording\"", "title": "" }, { "docid": "133235", "text": "\"Do I understand correctly, that we still can file as \"\"Married filing jointly\"\", just add Schedule C and Schedule SE for her? Yes. Business registration information letter she got once registered mentions that her due date for filing tax return is January 31, 2016. Does this prevent us from filing jointly (as far as I understand, I can't file my income before that date)? IRS sends no such letters. IRS also doesn't require any registration. Be careful, you might be a victim to a phishing attack here. In any case, sole proprietor files a regular individual tax return with the regular April 15th deadline. Do I understand correctly that we do not qualify as \"\"Family partnership\"\" (I do not participate in her business in any way other than giving her money for initial tools/materials purchase)? Yes. Do I understand correctly that she did not have to do regular estimated tax payments as business was not expected to generate income this year? You're asking or saying? How would we know what she expected? In any case, you can use your withholding (adjust the W4) to compensate.\"", "title": "" }, { "docid": "166977", "text": "If you sell through an intermediate who sets up the shop for you, odds are they collect and pay the sales tax for you. My experience is with publishing books through Amazon, where they definitely handle this for you. If you can find a retailer that will handle the tax implications, that might be a good reason to use them. It looks like Etsy uses a different model where you yourself are responsible for the sales tax, which requires you to register with your state (looks like this is the information for New York) and pay the taxes yourself on a regular basis; see this link for a simple guide. If you're doing this, you'll need to keep track of how much tax you owe from your sales each month, quarter, or year (depending on the state laws). You can usually be a sole proprietor, which is the easiest business structure to set up; if you want to limit your legal liability, or work with a partner, you may want to look into other forms of business structure, but for most craftspeople a sole proprietorship is fine to start out with. If you do a sole proprietorship, you can probably file the income on a 1040 Schedule C when you do your personal taxes each year.", "title": "" }, { "docid": "440370", "text": "The essential difference b/n ADR and a common share is that ADR do not have Voting rights. Common share has. There are some ADR that would in certain conditions get converted to common stock, but by and large most ADR's would remain ADR's without any voting rights. If you are an individual investor, this difference should not matter as rarely one would hold such a large number of shares to vote on General meeting on various issues. The other difference is that since many countries have regulations on who can buy common shares, for example in India an Non Resident cannot directly buy any share, hence he would buy ADR. Thus ADR would be priced more in the respective market if there is demand. For example Infosys Technologies, an India Company has ADR on NYSE. This is more expensive around 1.5 times the price of the common share available in India (at current exchange rate). Thus if you are able to invest with equal ease in HK (have broker / trading account etc), consider the taxation of the gains in HK as well the tax treatment in US for overseas gains then its recommended that you go for Common Stock in HK. Else it would make sense to buy in US.", "title": "" }, { "docid": "271568", "text": "\"From your explanation the Sole Trader option is more appropriate and certainly easier to manage. There are many differences but the pertinent and most important ones are as follows. The main difference in your case would be tax and administration. As a sole trader you would need to do a tax return once a year and if you earned less than £11.5k you wouldn't have to pay any UK tax, assuming you have no other income and are a \"\"standard\"\" tax payer. The current tax allowance is £11.5k although this can change. Submitting your own tax return is relatively straighforward although you may want to consult an accountant. It is generally easier to run as sole trader versus a Limited Company, ie less paperwork and beaureaucracy. If you go down the Limited Company route, the company would be liable to pay Corporation Tax on any profits and this process is more complicated and you would probably need an accountant to do that for you, which is likely to cost a few hundred pounds every year. You can do it yourself but the process is not as simple as doing your own income tax return. Also as a sole trader you can do what you like with any income, you can spend it and treat it as your own wages. You can't do that if you set up a Limited Company as the income is \"\"owned\"\" by the company and so you would need to in effect pay yourself a wage from the company. In other words it's more complex than if you are a sole trader. The main advantage to a Limited Company is that it is easier to sell the business if you want to at a later date. There is nothing stopping you setting up a Limited Company later on, after beign a sole trader if you want to. They can also be more tax-efficient but this would not be relevant to your case if you are earning relatively small sums, if your income increases then you may want to reconsider. You can see more information here: https://www.duport.co.uk/company-formation/sole-trader-vs-limited-company.php (I have been both a sole trader and also set up my own Limited Company)\"", "title": "" }, { "docid": "530119", "text": "I'm no tax expert by any means. I do know that a disreagarded entity is considered a sole proprietor for federal tax purposes. My understanding is that this means your personal tax year and your business tax year must be one and the same. Nevertheless, it is technically possible to have a non-calendar fiscal year as an individual. This is so rare that I'm unable to find a an IRS reference to this. The best reference I could find was this article written by two CPAs. If you really want to persue this, you basically need to talk with an accountant, since this is complicated, and required keeping propper accounting records for your personal life, in addition to your business. A ledger creqated after-the-fact by an accountant has been ruled insufficent. You really need to live by the fiscal year you choose.", "title": "" }, { "docid": "486744", "text": "This is a scam. Do you know why Bank of America is doing a refund? Did you own any accounts? Why is India involved in this? If Bank of America in US wants to transfer money to you in US, India is not involved at all. Stop all communications with the scammer and don't transfer any money.", "title": "" }, { "docid": "508754", "text": "\"I have checked with Bank of America, and they say the ONLY way to cash (or deposit, or otherwise get access to the funds represented by a check made out to my business) is to open a business account. They tell me this is a Federal regulation, and every bank will say the same thing. To do this, I need a state-issued \"\"dba\"\" certificate (from the county clerk's office) as well as an Employer ID Number (EIN) issued by the IRS. AND their CHEAPEST business banking account costs $15 / month. I think I can go to the bank that the check is drawn upon, and they will cash it, assuming I have documentation showing that I am the sole proprietor. But I'm not sure.... What a racket!!\"", "title": "" }, { "docid": "355897", "text": "\"First, point: The CRA wants you to start a business with a \"\"Reasonable expectation of profit\"\". They typically expect to see a profit within 5 years, so you may be inviting unwanted questions from future auditors by using a breakeven strategy. Second point: If the goal is to pay as little tax as possible, you may want to consider having the corporation pay you as little as possible. Corporate income taxes are much lower than personal income taxes, according to these two CRA links: How it works is that your company pays you little as an outright salary and offers you perks like a leased company car, expense account for lunch and entertainment, a mobile phone, computer, etc. The company owns all of this stuff and lets you use it as part of the job. The company pays for all this stuff with corporate pre-tax dollars as opposed to you paying for it with personal after-tax dollars. There are specifics on meals & entertainment which modify this slightly (you can claim 50%) but you get the idea. The actual rate difference will depend on your province of residence and your corporate income level. There is also a requirement for \"\"Reasonable Expenses\"\", such that the expenses have to be in line with what you are doing. If you need to travel to a conference each year, that would be a reasonable expense. Adding your family and making it a vacation for everyone would not. You can claim such expenses as a sole proprietor or a corporation. The sole-proprietorship option puts any after-expense profits into your pocket as taxable income, where the corporate structure allows the corporation to hold funds and limit the amount paid out to you. I've seen this strategy successfully done first-hand, but have not done it myself. I am not a lawyer or accountant, consult these professionals about this tax strategy before taking any action.\"", "title": "" } ]
5a8fa5525542995b4424207d	What characters was the actor behind Allan Quatermain in King Solomon's Mines known for?	[ { "docid": "493900", "text": "Patrick Wayne Swayze ( ; August 18, 1952 – September 14, 2009) was an American actor, dancer, and singer-songwriter. Having gained fame with appearances in films during the 1980s, Swayze became popular for playing tough guys and romantic lead males, gaining him a wide fan base with female audiences, and status as a teen idol and sex symbol.", "title": "" }, { "docid": "10862318", "text": "King Solomon's Mines is a 2004 American two-part television miniseries, the fifth film adaptation of the 1885 novel of the same name by Henry Rider Haggard. Starring Patrick Swayze as Allan Quartermain (it is spelled \"Allan Quartermain\" in the credits, unlike the book, which has \"Allan Quatermain\") and Alison Doody as Elizabeth Maitland, the film was produced by Hallmark Entertainment, and originally aired June 6, 2004 on Hallmark Channel.", "title": "" } ]	[ { "docid": "921502", "text": "Allan Quatermain is a fictional character, the protagonist in the novel \"King Solomon's Mines\".", "title": "" }, { "docid": "919129", "text": "Allan Quatermain is the protagonist of H. Rider Haggard's 1885 novel \"King Solomon's Mines\" and its sequels. \"Allan Quatermain\" was also the title of a book in this sequence.", "title": "" }, { "docid": "38807846", "text": "King Solomon's Treasure is a 1979 British-Canadian low-budget film based on the novels \"King Solomon's Mines\" and \"Allan Quatermain\" by H. Rider Haggard. It stars John Colicos as Allan Quatermain, as well as David McCallum, Britt Ekland, and Patrick Macnee who replaced Terry-Thomas.", "title": "" }, { "docid": "41425572", "text": "Allan Quatermain is a novel by H. Rider Haggard. It is the sequel to Haggard's novel \"King Solomon's Mines\".", "title": "" }, { "docid": "985537", "text": "Allan Quatermain and the Lost City of Gold is an adventure comedy film directed by Gary Nelson and released in West Germany on December 18, 1986, and in the United States on January 30, 1987. It is loosely based on the novel \"Allan Quatermain\" by H. Rider Haggard. It is the sequel to \"King Solomon's Mines\".", "title": "" }, { "docid": "10586147", "text": "She and Allan is a novel by H. Rider Haggard, first published in 1921. It brought together his two most popular characters, Ayesha from \"She\" (to which it serves as a prequel), and Allan Quatermain from \"King Solomon's Mines\". Along with the other three novels in the series, \"She and Allan\" was adapted into the 1935 film \"She\".", "title": "" }, { "docid": "81166", "text": "King Solomon's Mines (1885) is a popular novel by the English Victorian adventure writer and fabulist Sir H. Rider Haggard. It tells of a search of an unexplored region of Africa by a group of adventurers led by Allan Quatermain for the missing brother of one of the party. It is the first English adventure novel set in Africa, and is considered to be the genesis of the Lost World literary genre.", "title": "" }, { "docid": "3246173", "text": "José Silvestre is the name of two fictional characters in H. Rider Haggard's adventure novel \"King Solomon's Mines\". The elder of the two is a 16th-century Portuguese nobleman who first reached the Kukuana kingdom and the lost mines before dying. The second, who lives in the 19th century time period of the novel, is his descendant. The latter José lost his life after trying to cross the desert, but not before leaving the map of the road to the mines with the elephant hunter Allan Quatermain.", "title": "" }, { "docid": "4154303", "text": "Herbert William \"Bob\" Compton Bennett (15 January 1900 – 11 August 1974), better known as Compton Bennett, was an English film director, writer and producer. He is perhaps best known for directing the 1945 film \"The Seventh Veil\" and the 1950 version of the film \"King Solomon's Mines\", an adaptation of an Allan Quatermain story.", "title": "" }, { "docid": "41408178", "text": "Stella Fregelius: A Tale of Three Destinies is a 1904 novel by British writer H. Rider Haggard about a young inventor who falls in love with a mysterious stranger while he is engaged to another woman. As a novelist, Haggard is known primarily for his adventure novels. Among his most widely read and critically acclaimed novels are \"King Solomon's Mines\", \"Allan Quatermain\", and \"She\". After his publication of \"She\", Haggard wrote at least one novel a year every year until his death in 1925.", "title": "" }, { "docid": "20836583", "text": "Allan Quatermain and the Temple of Skulls is a 2008 direct-to-DVD adventure film created by American studio The Asylum. The film follows the adventures of explorer Allan Quatermain, and was filmed entirely on location in South Africa.", "title": "" }, { "docid": "36450149", "text": "Allan and the Holy Flower is a 1915 novel by H. Rider Haggard featuring Allan Quatermain. It first appeared serialised in \"The Windsor Magazine\". The plot involves Quatermain going on a trek into Africa to find a mysterious flower.", "title": "" }, { "docid": "39445979", "text": "Sir Sean Connery is a retired Scottish actor and producer. He was the first actor to have portrayed the literary character James Bond in a film, starring in seven Bond films between 1962 and 1983. He is also known for his roles as Jimmy Malone in \"The Untouchables\" (1987), for which he won an Academy Award for Best Supporting Actor, along with his portrayals of Mark Rutland in \"Marnie\" (1964), Juan Sánchez Villa-Lobos Ramírez in \"Highlander\" (1986), Henry Jones Sr. in \"Indiana Jones and the Last Crusade\" (1989), Captain Marko Aleksandrovich Ramius in \"The Hunt for Red October\" (1990), and Allan Quatermain in \"The League of Extraordinary Gentlemen\" (2003). Along with his Academy Award, Connery has won two BAFTA Awards, three Golden Globes, and a Henrietta Award.", "title": "" }, { "docid": "5473847", "text": "Sir Henry Curtis is a fictional character in a series of adventure novels by H. Rider Haggard. His Zulu name is Incubu, which means \"Elephant\". He is the constant companion and fellow traveler of Allan Quatermain.", "title": "" }, { "docid": "19765472", "text": "In Search of King Solomon's Mines is a travel book by Anglo-Afghan author, Tahir Shah.", "title": "" }, { "docid": "80952", "text": "King Solomon's Mines, H. Rider Haggard's 1885 adventure novel, has been adapted to the following films:", "title": "" }, { "docid": "10862322", "text": "King Solomon's Mines is a 1985 action adventure film, the fourth of five film adaptations of the 1885 novel of the same name by Henry Rider Haggard. It stars Richard Chamberlain, Sharon Stone, Herbert Lom and John Rhys-Davies. It was adapted by Gene Quintano and James R. Silke and directed by J. Lee Thompson. This version of the story was a light, comedic take, deliberately referring to, and parodying \"Indiana Jones\" (in which franchise actor Rhys-Davies appeared in two installments). It was filmed outside Harare in Zimbabwe.", "title": "" }, { "docid": "36936762", "text": "The Search for King Solomon's Mines is a documentary film based on the trail followed in Tahir Shah's 2002 book \"In Search of King Solomon's Mines\". After the initial journeys through Ethiopia that resulted in Shah's book, returned to the country with a film crew commissioned by National Geographical TV and Britain's Channel 4, to bring the search for the fabled mines to television. As a travel writer, having a film crew accompany him for the first time was a new experience for Shah. His work in researching books usually involves a low key method of gaining information and making contacts.", "title": "" }, { "docid": "41197220", "text": "Samson in King Solomon's Mines (Italian: \"Maciste nelle miniere de re Salmone\" is a 1964 Italian peplum film written and directed by Piero Regnoli.", "title": "" }, { "docid": "36114733", "text": "Marie is a 1912 novel by H. Rider Haggard featuring Allan Quatermain. The plot concerns Quatermain as a young man and involves his first marriage, to the Boer farm girl, Marie Marais. Their romance is opposed by Marie's anti-English father, and the villainous Pereira, who desires Marie. They are Voortrekkers who take part in the Great Trek whom Quatermain has to rescue.", "title": "" }, { "docid": "8905156", "text": "King Solomon's Mines is a 1937 British adventure film directed by Robert Stevenson and starring Paul Robeson, Cedric Hardwicke, Anna Lee, John Loder and Roland Young. The first of five film adaptations of the 1885 novel of the same name by Henry Rider Haggard, the film was produced by the Gaumont British Picture Corporation at Lime Grove Studios in Shepherd's Bush. Sets were designed by art director Alfred Junge. Although versions of \"King Solomon's Mines\" were released in 1950 and 1985, this film offering is considered to be the most faithful to the book.", "title": "" }, { "docid": "36141970", "text": "Child of Storm is a 1913 novel by H. Rider Haggard featuring Allan Quatermain. The plot is set in 1854-56 and concerns Quatermain hunting in Zululand and getting involved with Mameema, a beautiful African girl who causes great turmoil in the Zulu kingdom.", "title": "" }, { "docid": "52781918", "text": "Stuart Allan (born 1999 in Northern Virginia) is an American actor and voice actor. He is known for voicing the titular character of Damian Wayne in \"Son of Batman\", \"Batman vs. Robin\", \"\", \"Justice League vs. Teen Titans\" and \"\" and Russell Clay in \"\".", "title": "" }, { "docid": "7764053", "text": "The Librarian: Return to King Solomon's Mines is the second in \"The Librarian\" franchise of movies starring Noah Wyle as a librarian who protects a secret collection of artifacts. Gabrielle Anwar, Bob Newhart, Jane Curtin and Olympia Dukakis co-star. It is a sequel to 2004's \"\". The third film in the trilogy, \"\", was released in 2008.", "title": "" }, { "docid": "9467480", "text": "King Solomon's Mines is a 1950 Technicolor adventure film, the second of five film adaptations of the 1885 novel of the same name by Henry Rider Haggard. It stars Deborah Kerr, Stewart Granger and Richard Carlson. It was adapted by Helen Deutsch, directed by Compton Bennett and Andrew Marton and released by Metro-Goldwyn-Mayer.", "title": "" }, { "docid": "41416458", "text": "The Ivory Child is a novel by H. Rider Haggard featuring Allan Quatermain.", "title": "" }, { "docid": "41424019", "text": "The Treasure of the Lake is a novel by H Rider Haggard featuring Allan Quatermain.", "title": "" }, { "docid": "3038576", "text": "\"What You Leave Behind\" is the series finale of the television show \"\", the 175th and 176th overall episodes, and the 25th and 26th episodes of the . The episode was written by showrunner Ira Steven Behr and Hans Beimler and directed by Allan Kroeker. It originally aired on June 2, 1999.", "title": "" }, { "docid": "41416804", "text": "Heu Heu, or the Monster is a novel by H. Rider Haggard. Allan Quatermain tells the story of a monster in Rhodesia.", "title": "" }, { "docid": "32072084", "text": "Charles Quatermaine (30 December 1877 in Richmond, Surrey – August 1958 in Sussex) was a British stage and film actor. He appeared on Broadway and was the brother of Leon Quartermaine.", "title": "" } ]
1068	ScPif1p has reduced binding ability to G-rich ssDNA compared to non-G-rich ssDNA.	[ { "docid": "4429668", "text": "The Saccharomyces cerevisiae Pif1 helicase is the prototypical member of the Pif1 DNA helicase family, which is conserved from bacteria to humans. Here we show that exceptionally potent G-quadruplex unwinding is conserved among Pif1 helicases. Moreover, Pif1 helicases from organisms separated by more than 3 billion years of evolution suppressed DNA damage at G-quadruplex motifs in yeast. The G-quadruplex-induced damage generated in the absence of Pif1 helicases led to new genetic and epigenetic changes. Furthermore, when expressed in yeast, human PIF1 suppressed both G-quadruplex-associated DNA damage and telomere lengthening.", "title": "Pif1 family helicases suppress genome instability at G-quadruplex motifs" } ]	[ { "docid": "16217855", "text": "The product of the gene mutated in Bloom's syndrome, BLM, is a 3′–5′ DNA helicase belonging to the highly conserved RecQ family. In addition to a conventional DNA strand separation activity, BLM catalyzes both the disruption of non-B-form DNA, such as G-quadruplexes, and the branch migration of Holliday junctions. Here, we have characterized a new activity for BLM: the promotion of single-stranded DNA (ssDNA) annealing. This activity does not require Mg2+, is inhibited by ssDNA binding proteins and ATP, and is dependent on DNA length. Through analysis of various truncation mutants of BLM, we show that the C-terminal domain is essential for strand annealing and identify a 60 amino acid stretch of this domain as being important for both ssDNA binding and strand annealing. We present a model in which the ssDNA annealing activity of BLM facilitates its role in the processing of DNA intermediates that arise during repair of damaged replication forks.", "title": "The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA" }, { "docid": "15659108", "text": "Rad52 promotes the annealing of complementary strands of DNA bound by replication protein A (RPA) during discrete repair pathways. Here, we used a fluorescence resonance energy transfer (FRET) between two fluorescent dyes incorporated into DNA substrates to probe the mechanism by which human Rad52 (hRad52) interacts with and mediates annealing of ssDNA-hRPA complexes. Human Rad52 bound ssDNA or ssDNA-hRPA complex in two, concentration-dependent modes. At low hRad52 concentrations, ssDNA was wrapped around the circumference of the protein ring, while at higher protein concentrations, ssDNA was stretched between multiple hRad52 rings. Annealing by hRad52 occurred most efficiently when each complementary DNA strand or each ssDNA-hRPA complex was bound by hRad52 in a wrapped configuration, suggesting homology search and annealing occur via two hRad52-ssDNA complexes. In contrast to the wild type protein, hRad52(RQK/AAA) and hRad52(1-212) mutants with impaired ability to bind hRPA protein competed with hRPA for binding to ssDNA and failed to counteract hRPA-mediated duplex destabilization highlighting the importance of hRad52-hRPA interactions in promoting efficient DNA annealing.", "title": "Human Rad52 binds and wraps single-stranded DNA and mediates annealing via two hRad52–ssDNA complexes" }, { "docid": "799586", "text": "Bacteria encode a single-stranded DNA (ssDNA) binding protein (SSB) crucial for genome maintenance. In Bacillus subtilis and Streptococcus pneumoniae, an alternative SSB, SsbB, is expressed uniquely during competence for genetic transformation, but its precise role has been disappointingly obscure. Here, we report our investigations involving comparison of a null mutant (ssbB(-)) and a C-ter truncation (ssbBΔ7) of SsbB of S. pneumoniae, the latter constructed because SSBs' acidic tail has emerged as a key site for interactions with partner proteins. We provide evidence that SsbB directly protects internalized ssDNA. We show that SsbB is highly abundant, potentially allowing the binding of ~1.15 Mb ssDNA (half a genome equivalent); that it participates in the processing of ssDNA into recombinants; and that, at high DNA concentration, it is of crucial importance for chromosomal transformation whilst antagonizing plasmid transformation. While the latter observation explains a long-standing observation that plasmid transformation is very inefficient in S. pneumoniae (compared to chromosomal transformation), the former supports our previous suggestion that SsbB creates a reservoir of ssDNA, allowing successive recombination cycles. SsbBΔ7 fulfils the reservoir function, suggesting that SsbB C-ter is not necessary for processing protein(s) to access stored ssDNA. We propose that the evolutionary raison d'être of SsbB and its abundance is maintenance of this reservoir, which contributes to the genetic plasticity of S. pneumoniae by increasing the likelihood of multiple transformation events in the same cell.", "title": "Role of the Single-Stranded DNA–Binding Protein SsbB in Pneumococcal Transformation: Maintenance of a Reservoir for Genetic Plasticity" }, { "docid": "6386930", "text": "Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex-protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.", "title": "Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex." }, { "docid": "15305881", "text": "Deinococcus spp. are renowned for their amazing ability to recover rapidly from severe genomic fragmentation as a result of exposure to extreme levels of ionizing radiation or desiccation. Despite having been originally characterized over 50 years ago, the mechanism underlying this remarkable repair process is still poorly understood. Here, we report the 2.8 A structure of DdrB, a single-stranded DNA (ssDNA) binding protein unique to Deinococcus spp. that is crucial for recovery following DNA damage. DdrB forms a pentameric ring capable of binding single-stranded but not double-stranded DNA. Unexpectedly, the crystal structure reveals that DdrB comprises a novel fold that is structurally and topologically distinct from all other single-stranded binding (SSB) proteins characterized to date. The need for a unique ssDNA binding function in response to severe damage, suggests a distinct role for DdrB which may encompass not only standard SSB protein function in protection of ssDNA, but also more specialized roles in protein recruitment or DNA architecture maintenance. Possible mechanisms of DdrB action in damage recovery are discussed.", "title": "The structure of DdrB from Deinococcus: a new fold for single-stranded DNA binding proteins" }, { "docid": "2758012", "text": "Based on its in vitro unwinding activity on G-quadruplex (G4) DNA, the Bloom syndrome-associated helicase BLM is proposed to participate in telomere replication by aiding fork progression through G-rich telomeric DNA. Single molecule analysis of replicated DNA (SMARD) was used to determine the contribution of BLM helicase to telomere replication. In BLM-deficient cells, replication forks initiating from origins within the telomere, which copy the G-rich strand by leading strand synthesis, moved slower through the telomere compared with the adjacent subtelomere. Fork progression through the telomere was further slowed in the presence of a G4 stabilizer. Using a G4-specific antibody, we found that deficiency of BLM, or another G4-unwinding helicase, the Werner syndrome-associated helicase WRN, resulted in increased G4 structures in cells. Importantly, deficiency of either helicase led to greater increases in G4 DNA detected in the telomere compared with G4 seen genome-wide. Collectively, our findings are consistent with BLM helicase facilitating telomere replication by resolving G4 structures formed during copying of the G-rich strand by leading strand synthesis.", "title": "BLM helicase facilitates telomere replication during leading strand synthesis of telomeres" }, { "docid": "29098525", "text": "PriB is a primosomal protein required for re-initiation of replication in bacteria. We characterized and compared the DNA-binding properties of PriB from Salmonella enterica serovar Typhimurium LT2 (StPriB) and Escherichia coli (EcPriB). Only one residue of EcPriB, V6, was different in StPriB (replaced by A6). Previous structural information revealed that this residue is located on the putative dimer-dimer interface of PriB and is not involved in single-stranded DNA (ssDNA) binding. The cooperative binding mechanism of StPriB to DNA is, however, very different from that of EcPriB. Unlike EcPriB, which forms a single complex with ssDNAs of various lengths, StPriB forms two or more distinct complexes. Based on these results, as well as information on structure, binding modes for forming a stable complex of PriB with ssDNA of 25 nucleotides (nt), (EcPriB)25, and (StPriB)25 are proposed.", "title": "A single residue determines the cooperative binding property of a primosomal DNA replication protein, PriB, to single-stranded DNA." }, { "docid": "10486817", "text": "BACKGROUND Cellular nucleic acid binding protein (CNBP) has been implicated in vertebrate craniofacial development and in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human diseases by controlling cell proliferation and survival to mediate neural crest expansion. CNBP has been found to bind single-stranded nucleic acid and promote rearrangements of nucleic acid secondary structure in an ATP-independent manner, acting as a nucleic acid chaperone. METHODS A variety of methods were used, including cell viability assays, wound-scratch assays, chemotaxis assays, invasion assays, circular dichroic (CD) spectroscopy, NMR spectroscopy, chromatin immunoprecipitation, expression and purification of recombinant human CNBP, electrophoretic mobility shift assay (EMSA), surface plasmon resonance (SPR), fluorescence resonance energy transfer (FRET) analyses, luciferase reporter assay, Western blotting, and isothermal titration calorimetry (ITC). RESULTS Up-regulation of CNBP induced human fibrosarcoma cell death and suppressed fibrosarcoma cell motility and invasiveness. It was found that CNBP transcriptionally down-regulated the expression of heterogeneous ribonucleoprotein K (hnRNP K) through its conversion of a G-rich sequence into G-quadruplex in the promoter of hnRNP K. G-quadruplex stabilizing ligand tetra-(N-methyl-4-pyridyl) porphyrin (TMPyP4) could interact with and stabilize the G-quadruplex, resulting in downregulation of hnRNP K transcription. CONCLUSIONS CNBP overexpression caused increase of cell death and suppression of cell metastasis through its induction of G-quadruplex formation in the promoter of hnRNP K resulting in hnRNP K down-regulation. GENERAL SIGNIFICANCE The present result provided a new solution for controlling hnRNP K expression, which should shed light on new anticancer drug design and development.", "title": "Cellular nucleic acid binding protein suppresses tumor cell metastasis and induces tumor cell death by downregulating heterogeneous ribonucleoprotein K in fibrosarcoma cells." }, { "docid": "16472469", "text": "G-quadruplex (G4)-forming genomic sequences, including telomeres, represent natural replication fork barriers. Stalled replication forks can be stabilized and restarted by homologous recombination (HR), which also repairs DNA double-strand breaks (DSBs) arising at collapsed forks. We have previously shown that HR facilitates telomere replication. Here, we demonstrate that the replication efficiency of guanine-rich (G-rich) telomeric repeats is decreased significantly in cells lacking HR. Treatment with the G4-stabilizing compound pyridostatin (PDS) increases telomere fragility in BRCA2-deficient cells, suggesting that G4 formation drives telomere instability. Remarkably, PDS reduces proliferation of HR-defective cells by inducing DSB accumulation, checkpoint activation, and deregulated G2/M progression and by enhancing the replication defect intrinsic to HR deficiency. PDS toxicity extends to HR-defective cells that have acquired olaparib resistance through loss of 53BP1 or REV7. Altogether, these results highlight the therapeutic potential of G4-stabilizing drugs to selectively eliminate HR-compromised cells and tumors, including those resistant to PARP inhibition.", "title": "Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds" }, { "docid": "17897801", "text": "BACKGROUND Abciximab plus aspirin improves the TIMI 3 flow rate of the infarct-related artery in patients treated with either percutaneous coronary intervention or thrombolysis. The present study investigated whether the reperfusion efficacy of abciximab relates to modifications of clot architecture in patients admitted for acute myocardial infarction (AMI). METHODS AND RESULTS A total of 23 AMI patients in the Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long term follow-up (ADMIRAL) trial received, in a double-blind fashion, either abciximab (n=13) or placebo (n=10) before primary stenting. Viscoelastic (G' in dyne/cm(2)) and morphological (mean platelet aggregate surface area [SAG] in micrometer(2)) indexes of ex vivo platelet-rich clots (PRC) were assessed in a double-blind fashion before and after the bolus administration of abciximab or placebo. G' and SAG reflect the mechanical and morphological impact of activated platelets on the PRC fibrin network, respectively. Abciximab administration reduced G' by 63% (P=0.0001) and SAG by 65% (P=0.0007), and no effect was seen in the placebo group. These abciximab-related changes increased fibrin exposure as a consequence of the platelet-aggregate surface reduction and may have improved endogenous fibrinolysis. These effects were identified in all patients, independent of previous heparin administration. CONCLUSIONS Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.", "title": "Effects of Abciximab on the architecture of platelet-rich clots in patients with acute myocardial infarction undergoing primary coronary intervention." }, { "docid": "1914588", "text": "Single-stranded DNA-binding protein (SSB) plays an important role in DNA metabolism, such as in DNA replication, repair, and recombination, and is essential for cell survival. We characterized the single-stranded DNA (ssDNA)-binding properties of Pseudomonas aeruginosa PAO1 SSB (PaSSB) by using fluorescence quenching measurements and electrophoretic mobility shift analysis (EMSA). Analysis of purified PaSSB by gel filtration chromatography revealed a stable tetramer in solution. In fluorescence titrations, PaSSB bound 22-32 nucleotides (nt) per tetramer depending on salt concentration. Using EMSA, we characterized the stoichiometry of PaSSB complexed with a series of ssDNA homopolymers, and the size of the binding site was determined to be 29 ± 1 nt. Furthermore, EMSA results indicated that the dissociation constants of PaSSB for the first tetramer were less than those for the second tetramer. On the basis of these biophysical analyses, the ssDNA binding mode of PaSSB is expected to be noncooperative.", "title": "Characterization of a single-stranded DNA-binding protein from Pseudomonas aeruginosa PAO1." }, { "docid": "12207340", "text": "The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5'-terminated strands in a process termed end resection. End resection generates 3'-single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and DNA strand exchange, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5'-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3'-ssDNA-tailed intermediates. Initiation of resection commits a cell to repair a DSB by HR because long ssDNA overhangs are poor substrates for non-homologous end joining (NHEJ). Thus, the initiation of end resection has emerged as a critical control point for repair pathway choice. Here, I review recent studies on the mechanism of end resection and how this process is regulated to ensure the most appropriate repair outcome.", "title": "Mechanism and regulation of DNA end resection in eukaryotes." }, { "docid": "8698857", "text": "TNF expression of macrophages is under stringent translational control that depends on the p38 MAPK/MK2 pathway and the AU-rich element (ARE) in the TNF mRNA. Here, we elucidate the molecular mechanism of phosphorylation-regulated translation of TNF. We demonstrate that translation of the TNF-precursor at the ER requires expression of the ARE-binding and -stabilizing factor human antigen R (HuR) together with either activity of the p38 MAPK/MK2 pathway or the absence of the ARE-binding and -destabilizing factor tristetraprolin (TTP). We show that phosphorylation of TTP by MK2 decreases its affinity to the ARE, inhibits its ability to replace HuR, and permits HuR-mediated initiation of translation of TNF mRNA. Since translation of TTP's own mRNA is also regulated by this mechanism, an intrinsic feedback control of the inflammatory response is ensured. The phosphorylation-regulated TTP/HuR exchange at target mRNAs provides a reversible switch between unstable/non-translatable and stable/efficiently translated mRNAs.", "title": "The p38/MK2-Driven Exchange between Tristetraprolin and HuR Regulates AU–Rich Element–Dependent Translation" }, { "docid": "20083834", "text": "Background/Objective:To investigate the effect of soy protein containing isoflavones on homocysteine (Hcy), C-reactive protein (CRP), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1).Subject/Methods:In a randomized crossover design, 34 postmenopausal women consumed soy protein isolate (26±5 g protein containing 44±8 mg isoflavones per day) or milk protein isolate (26±5 g protein per day) for 6 weeks each. Fasting blood samples were collected at the end of each diet period and end points analyzed by enzyme-linked immunosorbent assay. Results:Concentrations of Hcy, CRP, sE-selectin, sVCAM-1 and sICAM-1 were not different between soy and milk diet treatments. Results did not differ by equol production status or by baseline lipid concentration. Adjustment for intake of folate and methionine did not alter the Hcy results. Conclusions:These data suggest that decreasing vascular inflammation and Hcy concentration are not likely mechanisms by which soy consumption reduces coronary heart disease risk.", "title": "Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women" }, { "docid": "13931771", "text": "Various specialized domains have been described in the cytosol and the nucleus; however, little is known about compartmentalization within the mitochondrial matrix. GRSF1 (G-rich sequence factor 1) is an RNA binding protein that was previously reported to localize in the cytosol. We found that an isoform of GRSF1 accumulates in discrete foci in the mitochondrial matrix. These foci are composed of nascent mitochondrial RNA and also contain RNase P, an enzyme that participates in mitochondrial RNA processing. GRSF1 was found to interact with RNase P and to be required for processing of both classical and tRNA-less RNA precursors. In its absence, cleavage of primary RNA transcripts is abnormal, leading to decreased expression of mitochondrially encoded proteins and mitochondrial dysfunction. Our findings suggest that the foci containing GRSF1 and RNase P correspond to sites where primary RNA transcripts converge to be processed. We have termed these large ribonucleoprotein structures \"mitochondrial RNA granules. \"", "title": "GRSF1 Regulates RNA Processing in Mitochondrial RNA Granules" }, { "docid": "20943272", "text": "ADAM13 is a member of the disintegrin and metalloprotease protein family that is expressed on cranial neural crest cells surface and is essential for their migration. ADAM13 is an active protease that can cleave fibronectin in vitro and remodel a fibronectin substrate in vivo. Using a recombinant secreted protein containing both disintegrin and cysteine-rich domains of ADAM13, we show that this \"adhesive\" region of the protein binds directly to fibronectin. Fibronectin fusion proteins corresponding to the various functional domains were used to define the second heparin-binding domain as the ADAM13 binding site. Mutation of the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of the recombinant disintegrin and cysteine-rich domains of ADAM13. We further show that the adhesive disintegrin and cysteine-rich domain of ADAM13 can promote cell adhesion via beta(1) integrins. This adhesion requires integrin activation and can be prevented by antibodies to the cysteine-rich domain of ADAM13 and beta(1) integrin. Finally, wild type, but not the E/A mutant of ADAM13 metalloprotease domain, can be shed from the cell surface, releasing the metalloprotease domain associated with the disintegrin and cysteine-rich domains. This suggests that ADAM13 shedding may involve its own metalloprotease activity and that the released protease may interact with both integrins and extracellular matrix proteins.", "title": "ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin." }, { "docid": "4422868", "text": "Intestinal cancer is initiated by Wnt-pathway-activating mutations in genes such as adenomatous polyposis coli (APC). As in most cancers, the cell of origin has remained elusive. In a previously established Lgr5 (leucine-rich-repeat containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen-inducible Cre recombinase is expressed in long-lived intestinal stem cells. Here we show that deletion of Apc in these stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fuelling a growing microadenoma. These microadenomas show unimpeded growth and develop into macroscopic adenomas within 3-5weeks. The distribution of Lgr5+ cells within stem-cell-derived adenomas indicates that a stem cell/progenitor cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in short-lived transit-amplifying cells using a different cre mouse, the growth of the induced microadenomas rapidly stalls. Even after 30weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia.", "title": "Crypt stem cells as the cells-of-origin of intestinal cancer" }, { "docid": "4442799", "text": "BACKGROUND Soy protein or its components may protect against the atherosclerotic cardiovascular disease (CVD) risk factors total homocysteine (tHcy), C-reactive protein (CRP), and excess body iron, which generally increase with menopause. OBJECTIVE The primary objective of this study was to determine the independent effect of the soy protein components isoflavones and phytate on CVD risk factors in postmenopausal women. The secondary objective was to identify factors [blood lipids, oxidative stress indexes, serum ferritin, plasma folate, plasma vitamin B-12, and body mass index (BMI)] contributing to tHcy and CRP concentrations. DESIGN In a double-blind, 6-wk study, 55 postmenopausal women aged 47-72 y were randomly assigned to 1 of 4 soy protein (40 g/d) isolate treatments: native phytate and native isoflavone (n = 14), native phytate and low isoflavone (n = 13), low phytate and native isoflavone (n = 14), or low phytate and low isoflavone (n = 14). We measured iron indexes, tHcy, CRP, and BMI. RESULTS Soy protein with native phytate significantly reduced tHcy (P = 0.017), transferrin saturation (P = 0.027), and ferritin (P = 0.029), whereas soy protein with native isoflavones had no effect on any variables. At baseline, BMI was highly correlated with tHcy (r = 0.39, P = 0.003) and CRP (r = 0.55, P < 0.0001), whereas HDL cholesterol was correlated with CRP (r = -0.30, P = 0.02). Multiple regression analysis showed that LDL cholesterol and BMI contributed significantly (R2= 19.9%, P = 0.003) to the overall variance in tHcy. CONCLUSION Consuming phytate-rich foods and maintaining a healthy weight may reduce atherosclerotic CVD risk factors in postmenopausal women.", "title": "Effects of soy isoflavones and phytate on homocysteine, C-reactive protein, and iron status in postmenopausal women." }, { "docid": "10874408", "text": "DNA double-strand breaks (DSBs), which are formed by the Spo11 protein, initiate meiotic recombination. Previous DSB-mapping studies have used rad50S or sae2Δ mutants, which are defective in break processing, to accumulate Spo11-linked DSBs, and report large (≥ 50 kb) “DSB-hot” regions that are separated by “DSB-cold” domains of similar size. Substantial recombination occurs in some DSB-cold regions, suggesting that DSB patterns are not normal in rad50S or sae2Δ mutants. We therefore developed a novel method to map genome-wide, single-strand DNA (ssDNA)–associated DSBs that accumulate in processing-capable, repair-defective dmc1Δ and dmc1Δ rad51Δ mutants. DSBs were observed at known hot spots, but also in most previously identified “DSB-cold” regions, including near centromeres and telomeres. Although approximately 40% of the genome is DSB-cold in rad50S mutants, analysis of meiotic ssDNA from dmc1Δ shows that most of these regions have substantial DSB activity. Southern blot assays of DSBs in selected regions in dmc1Δ, rad50S, and wild-type cells confirm these findings. Thus, DSBs are distributed much more uniformly than was previously believed. Comparisons of DSB signals in dmc1, dmc1 rad51, and dmc1 spo11 mutant strains identify Dmc1 as a critical strand-exchange activity genome-wide, and confirm previous conclusions that Spo11-induced lesions initiate all meiotic recombination.", "title": "Mapping Meiotic Single-Strand DNA Reveals a New Landscape of DNA Double-Strand Breaks in Saccharomyces cerevisiae" }, { "docid": "1583134", "text": "Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C→T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A→G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.", "title": "Positional cloning of the APECED gene" }, { "docid": "11742219", "text": "Galanin (GAL) is known to stimulate feeding behavior. This peptide has different properties and functions from other feeding stimulants, e.g., neuropeptide Y and agouti-related protein. Hypothalamic GAL is relatively unresponsive to food deprivation and to changes in corticosterone, glucose utilization, dietary carbohydrate and leptin. This indicates that this peptide is not essential under conditions when food is scarce or low-energy, high-carbohydrate diets are being consumed. In contrast, recent evidence suggests that GAL in the paraventricular nucleus (PVN) functions in close relation to dietary fat and alcohol. In particular, it mediates functions that allow animals to adapt to conditions of positive energy balance involving excess consumption of these nutrients. This peptide in the PVN is stimulated by a high-fat diet and also by alcohol. It is stimulated by an increase in circulating lipids caused by a fat-rich meal or alcohol consumption, and it rises during the middle of the active feeding cycle, when fat consumption and triglycerides naturally rise. When centrally injected, GAL in the PVN increases the consumption of food and alcohol. Moreover, it produces a significantly stronger feeding response in rats maintained on a fat-rich diet, which also promotes alcohol intake. This evidence supports the existence of non-homeostatic, positive feedback circuits between GAL and both dietary fat and alcohol. These circuits are believed to contribute to the large meal size, over-consumption of alcohol, and obesity which are generally associated with fat-rich foods.", "title": "Regulation and effects of hypothalamic galanin: relation to dietary fat, alcohol ingestion, circulating lipids and energy homeostasis." }, { "docid": "188911", "text": "Antigen-presenting, major histocompatibility complex (MHC) class II-rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II-negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent \"stroma. \" At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type.", "title": "Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor" }, { "docid": "15655418", "text": "Long-term memory and synaptic plasticity are thought to require the synthesis of new proteins at activated synapses. The CPEB family of RNA binding proteins, including Drosophila Orb2, has been implicated in this process. The precise mechanism by which these molecules regulate memory formation is however poorly understood. We used gene targeting and site-specific transgenesis to specifically modify the endogenous orb2 gene in order to investigate its role in long-term memory formation. We show that the Orb2A and Orb2B isoforms, while both essential, have distinct functions in memory formation. These two isoforms have common glutamine-rich and RNA-binding domains, yet Orb2A uniquely requires the former and Orb2B the latter. We further show that Orb2A induces Orb2 complexes in a manner dependent upon both its glutamine-rich region and neuronal activity. We propose that Orb2B acts as a conventional CPEB to regulate transport and/or translation of specific mRNAs, whereas Orb2A acts in an unconventional manner to form stable Orb2 complexes that are essential for memory to persist.", "title": "Drosophila CPEB Orb2A Mediates Memory Independent of Its RNA-Binding Domain" }, { "docid": "2014909", "text": "Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment.", "title": "Oncogenic mTOR signaling recruits myeloid-derived suppressor cells to promote tumor initiation" }, { "docid": "12922760", "text": "BACKGROUND G-quadruplexes (G4s) are stable non-canonical DNA secondary structures consisting of stacked arrays of four guanines, each held together by Hoogsteen hydrogen bonds. Sequences with the ability to form these structures in vitro, G4 motifs, are found throughout bacterial and eukaryotic genomes. The budding yeast Pif1 DNA helicase, as well as several bacterial Pif1 family helicases, unwind G4 structures robustly in vitro and suppress G4-induced DNA damage in S. cerevisiae in vivo. RESULTS We determined the genomic distribution and evolutionary conservation of G4 motifs in four fission yeast species and investigated the relationship between G4 motifs and Pfh1, the sole S. pombe Pif1 family helicase. Using chromatin immunoprecipitation combined with deep sequencing, we found that many G4 motifs in the S. pombe genome were associated with Pfh1. Cells depleted of Pfh1 had increased fork pausing and DNA damage near G4 motifs, as indicated by high DNA polymerase occupancy and phosphorylated histone H2A, respectively. In general, G4 motifs were underrepresented in genes. However, Pfh1-associated G4 motifs were located on the transcribed strand of highly transcribed genes significantly more often than expected, suggesting that Pfh1 has a function in replication or transcription at these sites. CONCLUSIONS In the absence of functional Pfh1, unresolved G4 structures cause fork pausing and DNA damage of the sort associated with human tumors.", "title": "The essential Schizosaccharomyces pombe Pfh1 DNA helicase promotes fork movement past G-quadruplex motifs to prevent DNA damage" }, { "docid": "432261", "text": "The generation of gene-edited animals using the CRISPRs/Cas9 system is based on microinjection into zygotes which is inefficient, time consuming and demands high technical skills. We report the optimization of an electroporation method for intact rat zygotes using sgRNAs and Cas9 protein in combination or not with ssODNs (~100 nt). This resulted in high frequency of knockouts, between 15 and 50% of analyzed animals. Importantly, using ssODNs as donor template resulted in precise knock-in mutations in 25-100% of analyzed animals, comparable to microinjection. Electroporation of long ssDNA or dsDNA donors successfully used in microinjection in the past did not allow generation of genome-edited animals despite dsDNA visualization within zygotes. Thus, simultaneous electroporation of a large number of intact rat zygotes is a rapid, simple, and efficient method for the generation of a variety of genome-edited rats.", "title": "Generation of gene-edited rats by delivery of CRISPR/Cas9 protein and donor DNA into intact zygotes using electroporation" }, { "docid": "42314147", "text": "Sp1-like proteins are characterized by three conserved C-terminal zinc finger motifs that bind GC-rich sequences found in promoters of numerous genes essential for mammalian cell homeostasis. These proteins behave as transcriptional activators or repressors. Although significant information has been reported on the molecular mechanisms by which Sp1-like activators function, relatively little is known about mechanisms for repressor proteins. Here we report the functional characterization of BTEB3, a ubiquitously expressed Sp1-like transcriptional repressor. GAL4 assays show that the N terminus of BTEB3 contains regions that can act as direct repressor domains. Immunoprecipitation assays reveal that BTEB3 interacts with the co-repressor mSin3A and the histone deacetylase protein HDAC-1. Gel shift assays demonstrate that BTEB3 specifically binds the BTE site, a well characterized GC-rich DNA element, with an affinity similar to that of Sp1. Reporter and gel shift assays in Chinese hamster ovary cells show that BTEB3 can also mediate repression by competing with Sp1 for BTE binding. Thus, the characterization of this protein expands the repertoire of BTEB-like members of the Sp1 family involved in transcriptional repression. Furthermore, our results suggest a mechanism of repression for BTEB3 involving direct repression by the N terminus via interaction with mSin3A and HDAC-1 and competition with Sp1 via the DNA-binding domain.", "title": "The Sp1-like protein BTEB3 inhibits transcription via the basic transcription element box by interacting with mSin3A and HDAC-1 co-repressors and competing with Sp1." }, { "docid": "2904102", "text": "RecQ family helicases function as safeguards of the genome. Unlike Escherichia coli, the Gram-positive Bacillus subtilis bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg(2+)-dependent DNA helicase activity with a 3' → 5' polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with E. coli RecQ. Surprisingly, RecQ[Bs] resembles the truncated Saccharomyces cerevisiae Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3'-overhang but is inactive on blunt-ended dsDNA and 5'-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5'-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.", "title": "Characterization of biochemical properties of Bacillus subtilis RecQ helicase." }, { "docid": "2679511", "text": "Werner's syndrome (WS) and Bloom's syndrome (BS) are cancer predisposition disorders caused by loss of function of the RecQ helicases WRN or BLM, respectively. BS and WS are characterized by replication defects, hyperrecombination events and chromosomal aberrations, which are hallmarks of cancer. Inefficient replication of the G-rich telomeric strand contributes to chromosome aberrations in WS cells, demonstrating a link between WRN, telomeres and genomic stability. Herein, we provide evidence that BLM also contributes to chromosome-end maintenance. Telomere defects (TDs) are observed in BLM-deficient cells at an elevated frequency, which is similar to cells lacking a functional WRN helicase. Loss of both helicases exacerbates TDs and chromosome aberrations, indicating that BLM and WRN function independently in telomere maintenance. BLM localization, particularly its recruitment to telomeres, changes in response to replication dysfunction, such as in WRN-deficient cells or after aphidicolin treatment. Exposure to replication challenge causes an increase in decatenated deoxyribonucleic acid (DNA) structures and late-replicating intermediates (LRIs), which are visible as BLM-covered ultra-fine bridges (UFBs) in anaphase. A subset of UFBs originates from telomeric DNA and their frequency correlates with telomere replication defects. We propose that the BLM complex contributes to telomere maintenance through its activity in resolving LRIs.", "title": "The BLM helicase contributes to telomere maintenance through processing of late-replicating intermediate structures" }, { "docid": "11360768", "text": "OBJECTIVE To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Major databases from inception to January 2012 without language restrictions. STUDY SELECTION Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. DATA SYNTHESIS Results summarised as relative risks for dichotomous data and mean differences for continuous data. RESULTS We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference -60 g, -120 to -10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. CONCLUSIONS Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.", "title": "Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence" } ]
947	What are useful indexes for rapid evaluation of country investment risk?	[ { "docid": "194682", "text": "Rather than using the Human Development Index or Ease of Doing Business, if you primary purpose is for investments, you need to consider the Country rating provided by various agencies like These would tell as to how good the country is for investment in general. Just to highlight a difference, China may not fare very high in Human Development Index, however right now from investment point of view its a pretty good market. once you have decided the countries, you can either invest in funds specalizing in these countries or if legally permitted invest directly into the leading stock index in such countries. If your intention is to start a business in these countries, then you need to look at some other indexes. http://www.standardandpoors.com/ratings/articles/en/us/?assetID=1245219962821 http://www.fitchratings.com/jsp/sector/Sector.faces?selectedTab=Overview&Ne=4293330737%2b11&N=0 http://v3.moodys.com/Pages/default.aspx", "title": "" } ]	[ { "docid": "425586", "text": "There is no typical return for an IRA. Understand that an IRA is not an investment type, it is just an account that gets special tax treatment by the Federal Government. The money in the IRA could be invested in almost anything including Gold, Stocks, Bonds, Cash, CDs, etc. So the question as phrased isn't exactly meaningful. It is kind of like asking what is the typical price of things if I use $10 bills. As for a 10.6% annualized return on your portfolio. That's not a bad return. At that rate you will double your investment (with compounding) every 7.2 years. Again, however, some context is needed. You can really only evaluate investment returns with your risk profile in mind. If you are invested in super safe investments like CDs, that is an absolutely incredible return. You compare it to several indexes, which is a good way to do it if you are investing in the types of investments tracked by those indexes.", "title": "" }, { "docid": "469599", "text": "The Investopedia article you linked to is a good start. Its key takeaway is that you should always consider risk-adjusted return when evaluating your portfolio. In general, investors seeking a higher level of return must face a higher likelihood of taking a loss (risk). Different types of stocks (large vs small; international vs US; different industry sectors) have different levels of historical risk and return. Not to mention stocks vs bonds or other financial instruments... So, it's key to make an apples-to-apples comparison against an appropriate benchmark. A benchmark will tell you how your portfolio is doing versus a comparable portfolio. An index, such as the S&P 500, is often used, because it tells you how your portfolio is doing compared against simply passively investing in a diversified basket of securities. First, I would start with analyzing your portfolio to understand its asset allocation. You can use a tool like the Morningstar X-Ray to do this. You may be happy with the asset allocation, or this tool may inform you to adjust your portfolio to meet your long-term goals. The next step will be to choose a benchmark. Given that you are investing primarily in non-US securities, you may want to pick a globally diversified index such as the Dow Jones Global Index. Depending on the region and stock characteristics you are investing in, you may want to pick a more specialized index, such as the ones listed here in this WSJ list. With your benchmark set, you can then see how your portfolio's returns compare to the index over time. IRR and ROI are helpful metrics in general, especially for corporate finance, but the comparison-based approach gives you a better picture of your portfolio's performance. You can still calculate your personal IRR, and make sure to include factors such as tax treatment and investment expenses that may not be fully reflected by just looking at benchmarks. Also, you can calculate the metrics listed in the Investopedia article, such as the Sharpe ratio, to give you another view on the risk-adjusted return.", "title": "" }, { "docid": "98461", "text": "There are some ETF's on the Indian market that invest in broad indexes in other countries Here's an article discussing this Be aware that such investments carry an additional risk you do not have when investing in your local market, which is 'currency risk' If for example you invest in a ETF that represents the US S&P500 index, and the US dollar weakens relative to the indian rupee, you could see the value if your investment in the US market go down, even if the index itself is 'up' (but not as much as the change in currency values). A lot of investment advisors recommend that you have at least 75% of your investments in things which are denominated in your local currency (well technically, the same currency as your liabilities), and no more than 25% invested internationally. In large part the reason for this advice is to reduce your exposure to currency risk.", "title": "" }, { "docid": "135879", "text": "If you are younger, and you not under undue pressure to buy a home at any particular time, investing in the market is a reasonable way to prepare. Your risk tolerance should be high. Understand that this means you may buy in 3-4 years instead of 1-2 if the market takes a down turn. It took ~3-4 years for the S&P 500 to recover from the 2008 crash. I doubt anything that severe is in the making, but there is always an element of risk involved in investing. If you and your family will be busting at the seams of your current rental in a year, then maybe the bond fund advice others have provided is a better option. If you are willing to be flexible, a more aggressive strategy might be appropriate. Likely, you want something along the lines of the Vanguard S&P 500 mutual fund - something that is diversified (a large number of stocks), in relatively safe companies (in this case the 500 companies that Standard and Poor's think are most likely to repay corporate bonds), and 'indexed' vice 'actively managed' (indexed funds have lower fees because they are using 'rules' to pick the stocks rather than paying a person to evaluate them.) It's going to depend on you and your situation - and regardless of what you choose consistency will be key: put your investment on automatic so it happens every month without your input.", "title": "" }, { "docid": "59468", "text": "First thing to know about investing is that you make money by taking risks. That means the possibility of losing money as well as making it. There are low risk investments that pretty much always pay out but they don't earn much. Making $200 a month on $10,000 is about 26% per year. That's vastly more than you are going to earn on low risk assets. If you want that kind of return, you can invest in a diversified portfolio of equities through an equity index fund. Some years you may make 26% or more. Other years you may make nothing or lose that much or more. On average you may earn maybe 7%-10% hopefully. Overall, investing is a game of making money over long horizons. It's very useful for putting away your $10k now and having hopefully more than that when it comes time to buy a house or retire or something some years into the future. You have to accept that you might also end up with less than $10K in the end, but you are more likely to make money than to use it. What you describe doesn't seem like a possible situation. In developed markets, you can't reliably expect anything close to the return you desire from assets that are unlikely to lose you money. It might be time to re-evaluate your financial goals. Do you want spending money now, or do you want to invest for use down the road?", "title": "" }, { "docid": "231863", "text": "\"The \"\"ideal world\"\" index fund of any asset class is a perfect percentage holding of all underlying assets with immediate rebalancing that aligns to every change in the index weighting while trading in a fully liquid market with zero transaction costs. One finance text book that describes this is Introduction to Finance: Markets, Investments, and Financial Management, see chapter 11. Practically, the transaction costs and liquidity make this unworkable. There are several deviations between what the \"\"ideal world algorithm\"\" (\"\"the algorithm\"\") says you should do and what is actually done. Each of these items addresses a real-world solution to various costs of managing a passive index fund. (And they are good solutions.) However, any deviation from the ideal index fund will have a risk. An investor evaluating their choices is left to pick the lowest fees with the least deviation from the ideal index fund. (It is customary to ignore whether the results are in excess or deficit to the ideal). So your formula is: This is also described in the above book.\"", "title": "" }, { "docid": "146632", "text": "\"Yes. There are several downsides to this strategy: You aren't taking into account commissions. If you pay $5 each time you buy or sell a stock, you may greatly reduce or even eliminate any possible gains you would make from trading such small amounts. This next point sounds obvious, but remember that you pay a commission on every trade regardless of profit, so every trade you make that you make at a loss also costs you commissions. Even if you make trades that are profitable more often than not, if you make quite a few trades with small amounts like this, your commissions may eat away all of your profits. Commissions represent a fixed cost, so their effect on your gains decreases proportionally with the amount of money you place at risk in each trade. Since you're in the US, you're required to follow the SEC rules on pattern day trading. From that link, \"\"FINRA rules define a “pattern day trader” as any customer who executes four or more “day trades” within five business days, provided that the number of day trades represents more than six percent of the customer’s total trades in the margin account for that same five business day period.\"\" If you trip this rule, you'll be required to maintain $25,000 in a margin brokerage account. If you can't maintain the balance, your account will be locked. Don't forget about capital gains taxes. Since you're holding these securities for less than a year, your gains will be taxed at your ordinary income tax rates. You can deduct your capital losses too (assuming you don't repurchase the same security within 30 days, because in that case, the wash sale rule prevents you from deducting the loss), but it's important to think about gains and losses in real terms, not nominal terms. The story is different if you make these trades in a tax-sheltered account like an IRA, but the other problems still apply. You're implicitly assuming that the stock's prices are skewed in the positive direction. Remember that you have limit orders placed at the upper and lower bounds of the range, so if the stock price decreases before it increases, your limit order at the lower bound will be triggered and you'll trade at a loss. If you're hoping to make a profit through buying low and selling high, you want a stock that hits its upper bound before hitting the lower bound the majority of the time. Unless you have data analysis (not just your intuition or a pattern you've talked yourself into from looking at a chart) to back this up, you're essentially gambling that more often than not, the stock price will increase before it decreases. It's dangerous to use any strategy that you haven't backtested extensively. Find several months or years of historical data, either intra-day or daily data, depending on the time frame you're using to trade, and simulate your strategy exactly. This helps you determine the potential profitability of your strategy, and it also forces you to decide on a plan for precisely when you want to invest. Do you invest as soon as the stock trades in a range (which algorithms can determine far better than intuition)? It also helps you figure out how to manage your risk and how much loss you're willing to accept. For risk management, using limit orders is a start, but see my point above about positively skewed prices. Limit orders aren't enough. In general, if an active investment strategy seems like a \"\"no-brainer\"\" or too good to be true, it's probably not viable. In general, as a retail investor, it's foolish to assume that no one else has thought of your simple active strategy to make easy money. I can promise you that someone has thought of it. Trading firms have quantitative researchers that are paid to think of and implement trading strategies all the time. If it's viable at any scale, they'll probably already have utilized it and arbitraged away the potential for small traders to make significant gains. Trust me, you're not the first person who thought of using limit orders to make \"\"easy money\"\" off volatile stocks. The fact that you're asking here and doing research before implementing this strategy, however, means that you're on the right track. It's always wise to research a strategy extensively before deploying it in the wild. To answer the question in your title, since it could be interpreted a little differently than the body of the question: No, there's nothing wrong with investing in volatile stocks, indexes, etc. I certainly do, and I'm sure many others on this site do as well. It's not the investing that gets you into trouble and costs you a lot of money; it's the rapid buying and selling and attempting to time the market that proves costly, which is what you're doing when you implicitly bet that the distribution of the stock's prices is positively skewed. To address the commission fee problem, assuming a fee of $8 per trade ... and a minimum of $100 profit per sale Commissions aren't your only problem, and counting on $100 profit per sale is a significant assumption. Look at point #4 above. Through your use of limit orders, you're making the implicit assumption that, more often than not, the price will trigger your upper limit order before your lower limit order. Here's a simple example; let's assume you have limit orders placed at +2 and -2 of your purchase price, and that triggering the limit order at +2 earns you $100 profit, while triggering the limit order at -2 incurs a loss of $100. Assume your commission is $5 on each trade. If your upper limit order is triggered, you earn a profit of 100 - 10 = 90, then set up the same set of limit orders again. If your lower limit order is triggered this time, you incur a loss of 100 + 10 = 110, so your net gain is 90 - 110 = -20. This is a perfect example of why, when taking into account transaction costs, even strategies that at first glance seem profitable mathematically can actually fail. If you set up the same situation again and incur a loss again (100 + 10 = 110), you're now down -20 - 110 = -130. To make a profit, you need to make two profitable trades, without incurring further losses. This is why point #4 is so important. Whenever you trade, it's critical to completely understand the risk you're taking and the bet you're actually making, not just the bet you think you're making. Also, according to my \"\"algorithm\"\" a sale only takes place once the stock rises by 1 or 2 points; otherwise the stock is held until it does. Does this mean you've removed the lower limit order? If yes, then you expose yourself to downside risk. What if the stock has traded within a range, then suddenly starts declining because of bad earnings reports or systemic risks (to name a few)? If you haven't removed the lower limit order, then point #4 still stands. However, I never specified that the trades have to be done within the same day. Let the investor open up 5 brokerage accounts at 5 different firms (for safeguarding against being labeled a \"\"Pattern Day Trader\"\"). Each account may only hold 1 security at any time, for the span of 1 business week. How do you control how long the security is held? You're using limit orders, which will be triggered when the stock price hits a certain level, regardless of when that happens. Maybe that will happen within a week, or maybe it will happen within the same day. Once again, the bet you're actually making is different from the bet you think you're making. Can you provide some algorithms or methods that do work for generating some extra cash on the side, aside from purchasing S&P 500 type index funds and waiting? When I purchase index funds, it's not to generate extra liquid cash on the side. I don't invest nearly enough to be able to purchase an index fund and earn substantial dividends. I don't want to get into any specific strategies because I'm not in the business of making investment recommendations, and I don't want to start. Furthermore, I don't think explicit investment recommendations are welcome here (unless it's describing why something is a bad idea), and I agree with that policy. I will make a couple of points, however. Understand your goals. Are you investing for retirement or a shorter horizon, e.g. some side income? You seem to know this already, but I include it for future readers. If a strategy seems too good to be true, it probably is. Educate yourself before designing a strategy. Research fundamental analysis, different types of orders (e.g., so you fully understand that you don't have control over when limit orders are executed), different sectors of the market if that's where your interests lie, etc. Personally, I find some sectors fascinating, so researching them thoroughly allows me to make informed investment decisions as well as learn about something that interests me. Understand your limits. How much money are you willing to risk and possibly lose? Do you have a risk management strategy in place to prevent unexpected losses? What are the costs of the risk management itself? Backtest, backtest, backtest. Ideally your backtesting and simulating should be identical to actual market conditions and incorporate all transaction costs and a wide range of historical data. Get other opinions. Evaluate those opinions with the same critical eye as I and others have evaluated your proposed strategy.\"", "title": "" }, { "docid": "188497", "text": "The idea of an index is that it is representative of the market (or a specific market segment) as a whole, so it will move as the market does. Thus, past performance is not really relevant, unless you want to bank on relative differences between different countries' economies. But that's not the point. By far the most important aspect when choosing index funds is the ongoing cost, usually expressed as Total Expense Ratio (TER), which tells you how much of your investment will be eaten up by trading fees and to pay the funds' operating costs (and profits). This is where index funds beat traditional actively managed funds - it should be below 0.5% The next question is how buying and selling the funds works and what costs it incurs. Do you have to open a dedicated account or can you use a brokerage account at your bank? Is there an account management fee? Do you have to buy the funds at a markup (can you get a discount on it)? Are there flat trading fees? Is there a minimum investment? What lot sizes are possible? Can you set up a monthly payment plan? Can you automatically reinvest dividends/coupons? Then of course you have to decide which index, i.e. which market you want to buy into. My answer in the other question apparently didn't make it clear, but I was talking only about stock indices. You should generally stick to broad, established indices like the MSCI World, S&P 500, Euro Stoxx, or in Australia the All Ordinaries. Among those, it makes some sense to just choose your home country's main index, because that eliminates currency risk and is also often cheaper. Alternatively, you might want to use the opportunity to diversify internationally so that if your country's economy tanks, you won't lose your job and see your investment take a dive. Finally, you should of course choose a well-established, reputable issuer. But this isn't really a business for startups (neither shady nor disruptively consumer-friendly) anyway.", "title": "" }, { "docid": "477646", "text": "\"Diversification is spreading your investments around so that one point of risk doesn't sink your whole portfolio. The effect of having a diversified portfolio is that you've always got something that's going up (though, the corollary is that you've also always got something going down... winning overall comes by picking investments worth investing in (not to state the obvious or anything :-) )) It's worth looking at the different types of risk you can mitigate with diversification: Company risk This is the risk that the company you bought actually sucks. For instance, you thought gold was going to go up, and so you bought a gold miner. Say there are only two -- ABC and XYZ. You buy XYZ. Then the CEO reveals their gold mine is played out, and the stock goes splat. You're wiped out. But gold does go up, and ABC does gangbusters, especially now they've got no competition. If you'd bought both XYZ and ABC, you would have diversified your company risk, and you would have been much better off. Say you invested $10K, $5K in each. XYZ goes to zero, and you lose that $5K. ABC goes up 120%, and is now worth $11K. So despite XYZ bankrupting, you're up 10% on your overall position. Sector risk You can categorize stocks by what \"\"sector\"\" they're in. We've already talked about one: gold miners. But there are many more, like utilities, bio-tech, transportation, banks, etc. Stocks in a sector will tend to move together, so you can be right about the company, but if the sector is out of favor, it's going to have a hard time going up. Lets extend the above example. What if you were wrong about gold going up? Then XYZ would still be bankrupt, and ABC would be making less money so they went down as well; say, 20%. At that point, you've only got $4K left. But say that besides gold, you also thought that banks were cheap. So, you split your investment between the gold miners and a couple of banks -- lets call them LMN and OP -- for $2500 each in XYZ, ABC, LMN, and OP. Say you were wrong about gold, but right about banks; LMN goes up 15%, and OP goes up 40%. At that point, your portfolio looks like this: XYZ start $2500 -100% end $0 ABC start $2500 +120% end $5500 LMN start $2500 +15% end $2875 OP start $2500 +40% end $3500 For a portfolio total of: $11,875, or a total gain of 18.75%. See how that works? Region/Country/Currency risk So, now what if everything's been going up in the USA, and everything seems so overpriced? Well, odds are, some area of the world is not over-bought. Like Brazil or England. So, you can buy some Brazilian or English companies, and diversify away from the USA. That way, if the market tanks here, those foreign companies aren't caught in it, and could still go up. This is the same idea as the sector risk, except it's location based, instead of business type based. There is an additional twist to this -- currencies. The Brits use the pound, and the Brazilians use the real. Most small investors don't think about this much, but the value of currencies, including our dollar, fluctuates. If the dollar has been strong, and the pound weak (as it has been, lately), then what happens if that changes? Say you own a British bank, and the dollar weakens and the pound strengthens. Even if that bank doesn't move at all, you would still make a gain. Example: You buy British bank BBB for 40 pounds a share, when each pound costs $1.20. Say after a while, BBB is still 40 pounds/share, but the dollar weakened and the pound strengthened, such that each pound is now worth $1.50. You could sell BBB, and because of the currency exchange once you've got it converted back to dollars you'd have a 25% gain. Market cap risk Sometimes big companies do well, sometimes it's small companies. The small caps are riskier but higher returning. When you think about it, small and mid cap stocks have much more \"\"room to run\"\" than large caps do. It's much easier to double a company worth $1 billion than it is to double a company worth $100 billion. Investment types Stocks aren't the only thing you can invest in. There's also bonds, convertible bonds, CDs, preferred stocks, options and futures. It can get pretty complicated, especially the last two. But each of these investment behaves differently; and again the idea is to have something going up all the time. The classical mix is stocks and bonds. The idea here is that when times are good, the stocks go up; when times are bad, the bonds go up (because they're safer, so more people want them), but mostly they're there to providing steady income and help keep your portfolio from cratering along with the stocks. Currently, this may not work out so well; stocks and bonds have been moving in sync for several years, and with interest rates so low they don't provide much income. So what does this mean to you? I'm going make some assumptions here based on your post. You said single index, self-managed, and don't lower overall risk (and return). I'm going to assume you're a small investor, young, you invest in ETFs, and the single index is the S&P 500 index ETF -- SPY. S&P 500 is, roughly, the 500 biggest companies in the USA. Further, it's weighted -- how much of each stock is in the index -- such that the bigger the company is, the bigger a percentage of the index it is. If slickcharts is right, the top 5 companies combined are already 11% of the index! (Apple, Microsoft, Exxon, Amazon, and Johnson & Johnson). The smallest, News Corp, is a measly 0.008% of the index. In other words, if all you're invested in is SPY, you're invested in a handfull of giant american companies, and a little bit of other stuff besides. To diversify: Company risk and sector risk aren't really relevant to you, since you want broad market ETFs; they've already got that covered. The first thing I would do is add some smaller companies -- get some ETFs for mid cap, and small cap value (not small cap growth; it sucks for structural reasons). Examples are IWR for mid-cap and VBR for small-cap value. After you've done that, and are comfortable with what you have, it may be time to branch out internationally. You can get ETFs for regions (such as the EU - check out IEV), or countries (like Japan - see EWJ). But you'd probably want to start with one that's \"\"all major countries that aren't the USA\"\" - check out EFA. In any case, don't go too crazy with it. As index investing goes, the S&P 500 is not a bad way to go. Feed in anything else a little bit at a time, and take the time to really understand what it is you're investing in. So for example, using the ETFs I mentioned, add in 10% each IWR and VBR. Then after you're comfortable, maybe add 10% EFA, and raise IWR to 20%. What the ultimate percentages are, of course, is something you have to decide for yourself. Or, you could just chuck it all and buy a single Target Date Retirement fund from, say, Vanguard or T. Rowe Price and just not worry about it.\"", "title": "" }, { "docid": "231195", "text": "I am not interested in watching stock exchange rates all day long. I just want to place it somewhere and let it grow Your intuition is spot on! To buy & hold is the sensible thing to do. There is no need to constantly monitor the stock market. To invest successfully you only need some basic pointers. People make it look like it's more complicated than it actually is for individual investors. You might find useful some wisdom pearls I wish I had learned even earlier. Stocks & Bonds are the best passive investment available. Stocks offer the best return, while bonds are reduce risk. The stock/bond allocation depends of your risk tolerance. Since you're as young as it gets, I would forget about bonds until later and go with a full stock portfolio. Banks are glorified money mausoleums; the interest you can get from them is rarely noticeable. Index investing is the best alternative. How so? Because 'you can't beat the market'. Nobody can; but people like to try and fail. So instead of trying, some fund managers simply track a market index (always successfully) while others try to beat it (consistently failing). Actively managed mutual funds have higher costs for the extra work involved. Avoid them like the plague. Look for a diversified index fund with low TER (Total Expense Ratio). These are the most important factors. Diversification will increase safety, while low costs guarantee that you get the most out of your money. Vanguard has truly good index funds, as well as Blackrock (iShares). Since you can't simply buy equity by yourself, you need a broker to buy and sell. Luckily, there are many good online brokers in Europe. What we're looking for in a broker is safety (run background checks, ask other wise individual investors that have taken time out of their schedules to read the small print) and that charges us with low fees. You probably can do this through the bank, but... well, it defeats its own purpose. US citizens have their 401(k) accounts. Very neat stuff. Check your country's law to see if you can make use of something similar to reduce the tax cost of investing. Your government will want a slice of those juicy dividends. An alternative is to buy an index fund on which dividends are not distributed, but are automatically reinvested instead. Some links for further reference: Investment 101, and why index investment rocks: However the author is based in the US, so you might find the next link useful. Investment for Europeans: Very useful to check specific information regarding European investing. Portfolio Ideas: You'll realise you don't actually need many equities, since the diversification is built-in the index funds. I hope this helps! There's not much more, but it's all condensed in a handful of blogs.", "title": "" }, { "docid": "200477", "text": "Firstly, sorry about the accident. I am afraid you will need to do your own legwork, because you cannot trust other people with your money. It's a good thing you do not need to rush. Take your time to learn things. One thing is certain, you cannot let your money sit in a bank - inflation will digest them. You need to learn about investing yourself, or you run a risk of someone taking advantage of you. And there are people who specialise in exploiting people who have money and no idea what to do with them. There is no other way, if you have money, you need to know how to deal with it, or you are likely to lose it all. Since you need to have monthly income and also income that makes more money to make further investments, you need to look at two most common investments that are safe enough and also give good returns on investment: Property and index funds. You might also have a look at National bonds as this is considered safest investment possible (country has to go bust for you to lose money), but you are too young for that. Young = you can take more risk so Property and shares (indexes). You want to have your property investments in a country that is stable and has a good ROI (like Netherlands or Lithuania). Listen to some audio lectures: https://www.audible.co.uk/pd/Health-Personal-Development/Investing-in-Real-Estate-6th-Edition-Audiobook/B008SEH1R0 https://www.audible.co.uk/pd/Business/The-Secrets-of-Buy-to-Let-Success-Audiobook/B00UVVM222 https://www.audible.co.uk/pd/Non-fiction/Economics-3rd-Edition-Audiobook/B00D8J7VUC https://www.audible.co.uk/pd/Advanced-Investments-Part-1-Audiobook/B00HU81B80 After you sorted your investment strategy, you might want to move to a country that is Expat friendly and has lower living costs than US and you should be able to live like a king... best of luck.", "title": "" }, { "docid": "568624", "text": "Index funds are well-known to give the best long-term investment. Are they? Maybe not all the time! If you had invested in an index fund tracking the S&P500 at the start of 2000 you would still be behind in terms of capital appreciation when taking inflation into considerations. Your only returns in 13.5 years would have been any dividends you may have received. See the monthly chart of the S&P500 below. Diversification can be good for your overall returns, but diversification simply for diversification sake is as you said, a way of reducing your overall returns in order of smoothing out your equity curve. After looking up indexes for various countries the only one that had made decent returns over a 13.5 year period was the Indian BSE 30 index, almost 400% over 13.5 years, although it also has gone nowhere since the end of 2007 (5.5 years). See monthly chart below. So investing internationally (especially in developing countries when developed nations are stagnating) can improve your returns, but I would learn about the various international markets first before plunging straight in. Regarding investing in an Index fund vs direct investment in a select group of shares, I did a search on the US markets with the following criteria on the 3rd January 2000: If the resulting top 10 from the search were bought on 3rd January 2000 and held up until the close of the market on the 19th June 2013, the results would be as per the table below: The result, almost 250% return in 13.5 years compared to almost no return if you had invested into the whole S&P 500 Index. Note, this table lists only the top ten from the search without screening through the charts, and no risk management was applied (if risk management was applied the 4 losses of 40%+ would have been limited to a maximum of 20%, but possibly much smaller losses or even for gains, as they might have gone into positive territory before coming back down - as I have not looked at any of the charts I cannot confirm this). This is one simple example how selecting good shares can result in much better returns than investing into a whole Index, as you are not pulled down by the bad stocks.", "title": "" }, { "docid": "306232", "text": "\"General advice is to keep 6 months worth of income liquid -- in your case, you might want to leave 1 year liquid since, even though your income is stable now, it is not static (i.e., you're not drawing salary from an employer). The rest of it? If you don't plan on using it for any big purchases in the next 5 or so years, invest it. If you don't, you will probably lose money in the long term due to inflation (how's that for a risk? :). There are plenty of options for the risk averse, many of which handily beat inflation, though without knowing your country of residence, it's hard to say. In all likelihood, though, you'll want to invest in index funds -- such as ETFs -- that basically track industries, rather than individual companies. This is basically free portfolio diversity -- they lose money only when an entire sector loses value. Though even with funds of this type, you still want to ensure you purchase multiple different funds that track different industries. Don't just toss all of your funds into an IT index, for example. Before buying, just look at the history of the fund and make sure it has had a general upward trajectory since 2008 (I've bought a few ETFs that remained static...not what we're looking for in an investment!). If the brokerage account you choose doesn't offer commission free trades on any of the funds you want (personally, I use Schwab and their ETF portfolio), try to \"\"buy in bulk.\"\" That way you're not spending so much on trades. There are other considerations (many indexed funds have high management costs, but if you go with ETFs, they don't, and there's the question of dividends, etc), but that is getting into the weeds as far as investing knowledge is concerned. Beyond that, just keep in mind it'll take 1-2 weeks for you to see that money if you need it, and there's obviously no guarantee it'll be there if you do need it for an emergency.\"", "title": "" }, { "docid": "60032", "text": "\"This turned out be a lot longer than I expected. So, here's the overview. Despite the presence of asset allocation calculators and what not, this is a subjective matter. Only you know how much risk you are willing to take. You seem to be aware of one rule of thumb, namely that with a longer investing horizon you can stand to take on more risk. However, how much risk you should take is subject to your own risk aversion. Honestly, the best way to answer your questions is to educate yourself about the individual topics. There are just too many variables to provide neat, concise answers to such a broad question. There are no easy ways around this. You should not blindly rely on the opinions of others, but rather use your own judgment to asses their advice. Some of the links I provide in the main text: S&P 500: Total and Inflation-Adjusted Historical Returns 10-year index fund returns The Motley Fool Risk aversion Disclaimer: These are the opinions of an enthusiastic amateur. Why should I invest 20% in domestic large cap and 10% in developing markets instead of 10% in domestic large cap and 20% in developing markets? Should I invest in REITs? Why or why not? Simply put, developing markets are very risky. Even if you have a long investment horizon, you should pace yourself and not take on too much risk. How much is \"\"too much\"\" is ultimately subjective. Specific to why 10% in developing vs 20% in large cap, it is probably because 10% seems like a reasonable amount of your total portfolio to gamble. Another way to look at this is to consider that 10% as gone, because it is invested in very risky markets. So, if you're willing to take a 20% haircut, then by all means do that. However, realize that you may be throwing 1/5 of your money out the window. Meanwhile, REITs can be quite risky as investing in the real estate market itself can be quite risky. One reason is that the assets are very much fixed in place and thus can not be liquidated in the same way as other assets. Thus, you are subject to the vicissitudes of a relatively small market. Another issue is the large capital outlays required for most commercial building projects, thus typically requiring quite a bit of credit and risk. Another way to put it: Donald Trump made his name in real estate, but it was (and still is) a very bumpy ride. Yet another way to put it: you have to build it before they will come and there is no guarantee that they will like what you built. What mutual funds or index funds should I investigate to implement these strategies? I would generally avoid actively managed mutual funds, due to the expenses. They can seriously eat into the returns. There is a reason that the most mutual funds compare themselves to the Lipper average instead of something like the S&P 500. All of those costs involved in managing a mutual fund (teams of people and trading costs) tend to weigh down on them quite heavily. As the Motley Fool expounded on years ago, if you can not do better than the S&P 500, you should save yourself the headaches and simply invest in an S&P 500 index fund. That said, depending on your skill (and luck) picking stocks (or even funds), you may very well have been able to beat the S&P 500 over the past 10 years. Of course, you may have also done a whole lot worse. This article discusses the performance of the S&P 500 over the past 60 years. As you can see, the past 10 years have been a very bumpy ride yielding in a negative return. Again, keep in mind that you could have done much worse with other investments. That site, Simple Stock Investing may be a good place to start educating yourself. I am not familiar with the site, so do not take this as an endorsement. A quick once-over of the material on the site leads me to believe that it may provide a good bit of information in readily digestible forms. The Motley Fool was a favorite site of mine in the past for the individual investor. However, they seem to have turned to the dark side, charging for much of their advice. That said, it may still be a good place to get started. You may also decide that it is worth paying for their advice. This blog post, though dated, compares some Vanguard index funds and is a light introduction into the contrarian view of investing. Simply put, this view holds that one should not be a lemming following the crowd, rather one should do the opposite of what everyone else is doing. One strong argument in favor of this view is the fact that as more people pile onto an investing strategy or into a particular market, the yields thin out and the risk of a correction (i.e. a downturn) increases. In the worst case, this leads to a bubble, which corrects itself suddenly (or \"\"pops\"\" thus the term \"\"bubble\"\") leading to quite a bit of pain for the unprepared participants. An unprepared participant is one who is not hedged properly. Basically, this means they were not invested in other markets/strategies that would increase in yield as a result of the event that caused the bubble to pop. Note that the recent housing bubble and resulting credit crunch beat quite heavily on the both the stock and bond markets. So, the easy hedge for stocks being bonds did not necessarily work out so well. This makes sense, as the housing bubble burst due to concerns over easy credit. Unfortunately, I don't have any good resources on hand that may provide starting points or discuss the various investing strategies. I must admit that I am turning my interests back to investing after a hiatus. As I stated, I used to really like the Motley Fool, but now I am somewhat suspicious of them. The main reason is the fact that as they were exploring alternatives to advertising driven revenue for their site, they promised to always have free resources available for those unwilling to pay for their advice. A cursory review of their site does show a decent amount of general investing information, so take these words with a grain of salt. (Another reason I am suspicious of them is the fact that they \"\"spammed\"\" me with lots of enticements to pay for their advice which seemed just like the type of advice they spoke against.) Anyway, time to put the soapbox away. As I do that though, I should explain the reason for this soapboxing. Simply put, investing is a risky endeavor, any way you slice it. You can never eliminate risk, you can only hope to reduce it to an acceptable level. What is acceptable is subject to your situation and to the magnitude of your risk aversion. Ultimately, it is rather subjective and you should not blindly follow someone else's opinion (professional or otherwise). Point being, use your judgment to evaluate anything you read about investing. If it sounds too good to be true, it probably is. If someone purports to have some strategy for guaranteed (steady) returns, be very suspicious of it. (Read up on the Bernard Madoff scandal.) If someone is putting on a heavy sales pitch, be weary. Be especially suspicious of anyone asking you to pay for their advice before giving you any solid understanding of their strategy. Sure, many people want to get paid for their advice in some way (in fact, I am getting \"\"paid\"\" with reputation on this site). However, if they take the sketchy approach of a slimy salesmen, they are likely making more money from selling their strategy, than they are from the advice itself. Most likely, if they were getting outsized returns from their strategy they would keep quiet about it and continue using it themselves. As stated before, the more people pile onto a strategy, the smaller the returns. The typical model for selling is to make money from the sale. When the item being sold is an intangible good, your risk as a buyer increases. You may wonder why I have written at length without much discussion of asset allocation. One reason is that I am still a relative neophyte and have a mostly high level understanding of the various strategies. While I feel confident enough in my understanding for my own purposes, I do not necessarily feel confident creating an asset allocation strategy for someone else. The more important reason is that this is a subjective matter with a lot of variables to consider. If you want a quick and simple answer, I am afraid you will be disappointed. The best approach is to educate yourself and make these decisions for yourself. Hence, my attempt to educate you as best as I can at this point in time. Personally, I suggest you do what I did. Start reading the Wall Street Journal every day. (An acceptable substitute may be the business section of the New York Times.) At first you will be overwhelmed with information, but in the long run it will pay off. Another good piece of advice is to be patient and not rush into investing. If you are in a hurry to determine how you should invest in a 401(k) or other such investment vehicle due to a desire to take advantage of an employer's matching funds, then I would place my money in an S&P 500 index fund. I would also explore placing some of that money into broad index funds from other regions of the globe. The reason for broad index funds is to provide some protection from the normal fluctuations and to reduce the risk of a sudden downturn causing you a lot pain while you determine the best approach for yourself. In this scenario, think more about capital preservation and hedging against inflation then about \"\"beating\"\" the market.\"", "title": "" }, { "docid": "259145", "text": "\"Is evaluating stocks just a loss of time if the stock is traded very much? Not at all! Making sound investment decisions based on fundamental analysis of companies will help you to do decide whether a given company is right for you and your risk appetite. Investing is not a zero-sum game, and you can achieve a positive long-term (or short-term, depending on what you're after) outcome for yourself without compromising your ability to sleep at night if you take the time to become acquainted with the companies that you are investing in. How can you ensure that your evaluation is more precise than the market ones which consists of the evaluation of thousands of people and professionals? For the average individual, the answer is often simply \"\"you probably cannot\"\". But you don't have to set the bar that high - what you can do is ensure that your evaluation gives you a better understanding of your investment and allows you to better align it with your investment objectives. You don't have to beat the professionals, you just have to lose less money than you would by paying them to make the decision for you.\"", "title": "" }, { "docid": "144261", "text": "\"Index funds are well-known to give the best long-term investment. Not exactly. Indexes give the best long term performance when compared to actively managing investments directly in the underlying stocks. That is, if you compare an S&P500 index to trying to pick stocks that are part of it, you're more likely to succeed with blindly following the index than trying to actively beat it. That said, no-one promises that investing in S&P500 is better than investing in DJIA, for example. These are two different indexes tracking different stocks and areas. So when advisers say \"\"diversify\"\" they don't mean it that you should diversify between different stocks that build up the S&P500 index. They mean that you should diversify your investments in different areas. Some in S&P500, some in DJIA, some in international indexes, some in bond indexes, etc. Still, investing in various indexes will likely yield better results than actively managing the investments trying to beat those indexes, but you should not invest in only one, and that is the meaning of diversification. In the comments you asked \"\"why diversify at all?\"\", and that is entirely a different question from your original \"\"what diversification is?\"\". You diversify to reduce the risk of loss from one side, and widen the net for gains from another. The thing is that any single investment can eventually fail, regardless of how it performed before. You can see that the S&P500 index lost 50% of its value twice within ten years, whereas before it was doubling itself every several years. Many people who were only invested in that index (or what's underlying to it) lost a lot of money. But consider you've diversified, and in the last 20 years you've invested in a blend of indexes that include the S&P500, but also other investments like S&P BSE SENSEX mentioned by Victor below. You would reduce your risk of loss on the American market by increasing your gains on the Indian market. Add to the mix soaring Chinese Real Estate market during the time of the collapse of the US real-estate, gains on the dollar losing its value by investing in other currencies (Canadian dollar, for example), etc. There are many risks, and by diversifying you mitigate them, and also have a chance to create other potential gains. Now, another question is why invest in indexes. That has been answered before on this site. It is my opinion that some methods of investing are just gambling by trying to catch the wave and they will almost always fail, and rarely will individual stock picking beat the market. Of course, after the fact its easy to be smart and pick the winning stocks. But the problem is to be able to predict those charts ahead of time.\"", "title": "" }, { "docid": "293679", "text": "Googling vanguard target asset allocation led me to this page on the Bogleheads wiki which has detailed breakdowns of the Target Retirement funds; that page in turn has a link to this Vanguard PDF which goes into a good level of detail on the construction of these funds' portfolios. I excerpt: (To the question of why so much weight in equities:) In our view, two important considerations justify an expectation of an equity risk premium. The first is the historical record: In the past, and in many countries, stock market investors have been rewarded with such a premium. ... Historically, bond returns have lagged equity returns by about 5–6 percentage points, annualized—amounting to an enormous return differential in most circumstances over longer time periods. Consequently, retirement savers investing only in “safe” assets must dramatically increase their savings rates to compensate for the lower expected returns those investments offer. ... The second strategic principle underlying our glidepath construction—that younger investors are better able to withstand risk—recognizes that an individual’s total net worth consists of both their current financial holdings and their future work earnings. For younger individuals, the majority of their ultimate retirement wealth is in the form of what they will earn in the future, or their “human capital.” Therefore, a large commitment to stocks in a younger person’s portfolio may be appropriate to balance and diversify risk exposure to work-related earnings (To the question of how the exact allocations were decided:) As part of the process of evaluating and identifying an appropriate glide path given this theoretical framework, we ran various financial simulations using the Vanguard Capital Markets Model. We examined different risk-reward scenarios and the potential implications of different glide paths and TDF approaches. The PDF is highly readable, I would say, and includes references to quant articles, for those that like that sort of thing.", "title": "" }, { "docid": "501395", "text": "\"Those who say a person should invest in riskier assets when young are those who equate higher returns with higher risk. I would argue that any investment you do not understand is risky and allows you to lose money at a more rapid rate than someone who understands the investment. The way to reduce risk is to learn about what you want to invest in before you invest in it. Learning afterward can be a very expensive proposition, possibly costing you your retirement. Warren Buffet told the story on Bloomberg Radio in late 2013 of how he read everything in his local library on investing as a teenager and when his family moved to Washington he realized he had the entire Library of Congress at his disposal. One of Mr. Buffett's famous quotes when asked why he doesn't invest in the tech sector was: \"\"I don't invest in what I do not understand.\"\". There are several major asset classes: Paper (stocks, bonds, mutual funds, currency), Commodities (silver, gold, oil), Businesses (creation, purchase or partnership as opposed to common stock ownership) and Real Estate (rental properties, flips, land development). Pick one that interests you and learn everything about it that you can before investing. This will allow you to minimize and mitigate risks while increasing the rewards.\"", "title": "" }, { "docid": "349417", "text": "Your definition of 'outside your country' might need some redefinition, as there are three different things going on here . . . Your financial adviser appears to be highlighting the currency risk associated with point three. However, consider these risk scenarios . . . A) Your country enters a period of severe financial difficulty, and money markets shut down. Your brokerage becomes insolvent, and your investments are lost. In this scenario the fact of whether your investments were in an overseas index such as the S&P, or were purchased from an account denominated in a different currency, would be irrelevant. The only thing that would have mitigated this scenario is an account with an overseas broker. B) Your country's stock market enters a sustained and deep bear market, decimating the value of shares in its companies. In this scenario the fact of whether your investments were made in from a brokerage overseas, or were purchased from an account denominated in a different currency, would be irrelevant. The only thing that would have mitigate this scenario is investment in shares and indices outside your home country. Your adviser has a good point; as long as you intend to enjoy your retirement in your home country then it might be advisable to remove currency risk by holding an account in Rupees. However, you might like to consider reducing the other forms of risk by holding non-Indian securities to create a globally diversified portfolio, and also placing some of your capital in an account with a broker outside your home country (this may be very difficult to do in practice).", "title": "" }, { "docid": "476517", "text": "Your idea is a good one, but, as usual, the devil is in the details, and implementation might not be as easy as you think. The comments on the question have pointed out your Steps 2 and 4 are not necessarily the best way of doing things, and that perhaps keeping the principal amount invested in the same fund instead of taking it all out and re-investing it in a similar, but different, fund might be better. The other points for you to consider are as follows. How do you identify which of the thousands of conventional mutual funds and ETFs is the average-risk / high-gain mutual fund into which you will place your initial investment? Broadly speaking, most actively managed mutual fund with average risk are likely to give you less-than-average gains over long periods of time. The unfortunate truth, to which many pay only Lipper service, is that X% of actively managed mutual funds in a specific category failed to beat the average gain of all funds in that category, or the corresponding index, e.g. S&P 500 Index for large-stock mutual funds, over the past N years, where X is generally between 70 and 100, and N is 5, 10, 15 etc. Indeed, one of the arguments in favor of investing in a very low-cost index fund is that you are effectively guaranteed the average gain (or loss :-(, don't forget the possibility of loss). This, of course, is also the argument used against investing in index funds. Why invest in boring index funds and settle for average gains (at essentially no risk of not getting the average performance: average performance is close to guaranteed) when you can get much more out of your investments by investing in a fund that is among the (100-X)% funds that had better than average returns? The difficulty is that which funds are X-rated and which non-X-rated (i.e. rated G = good or PG = pretty good), is known only in hindsight whereas what you need is foresight. As everyone will tell you, past performance does not guarantee future results. As someone (John Bogle?) said, when you invest in a mutual fund, you are in the position of a rower in rowboat: you can see where you have been but not where you are going. In summary, implementation of your strategy needs a good crystal ball to look into the future. There is no such things as a guaranteed bond fund. They also have risks though not necessarily the same as in a stock mutual fund. You need to have a Plan B in mind in case your chosen mutual fund takes a longer time than expected to return the 10% gain that you want to use to trigger profit-taking and investment of the gain into a low-risk bond fund, and also maybe a Plan C in case the vagaries of the market cause your chosen mutual fund to have negative return for some time. What is the exit strategy?", "title": "" }, { "docid": "113786", "text": "\"There are two umbrellas in investing: active management and passive management. Passive management is based on the idea \"\"you can't beat the market.\"\" Passive investors believe in the efficient markets hypothesis: \"\"the market interprets all information about an asset, so price is equal to underlying value\"\". Another idea in this field is that there's a minimum risk associated with any given return. You can't increase your expected return without assuming more risk. To see it graphically: As expected return goes up, so does risk. If we stat with a portfolio of 100 bonds, then remove 30 bonds and add 30 stocks, we'll have a portfolio that's 70% bonds/30% stocks. Turns out that this makes expected return increase and lower risk because of diversification. Markowitz showed that you could reduce the overall portfolio risk by adding a riskier, but uncorrelated, asset! Basically, if your entire portfolio is US stocks, then you'll lose money whenever US stocks fall. But, if you have half US stocks, quarter US bonds, and quarter European stocks, then even if the US market tanks, half your portfolio will be unaffected (theoretically). Adding different types of uncorrelated assets can reduce risk and increase returns. Let's tie this all together. We should get a variety of stocks to reduce our risk, and we can't beat the market by security selection. Ideally, we ought to buy nearly every stock in the market so that So what's our solution? Why, the exchange traded fund (ETF) of course! An ETF is basically a bunch of stocks that trade as a single ticker symbol. For example, consider the SPDR S&P 500 (SPY). You can purchase a unit of \"\"SPY\"\" and it will move up/down proportional to the S&P 500. This gives us diversification among stocks, to prevent any significant downside while limiting our upside. How do we diversify across asset classes? Luckily, we can purchase ETF's for almost anything: Gold ETF's (commodities), US bond ETF's (domestic bonds), International stock ETFs, Intl. bonds ETFs, etc. So, we can buy ETF's to give us exposure to various asset classes, thus diversifying among asset classes and within each asset class. Determining what % of our portfolio to put in any given asset class is known as asset allocation and some people say up to 90% of portfolio returns can be determined by asset allocation. That pretty much sums up passive management. The idea is to buy ETFs across asset classes and just leave them. You can readjust your portfolio holdings periodically, but otherwise there is no rapid trading. Now the other umbrella is active management. The unifying idea is that you can generate superior returns by stock selection. Active investors reject the idea of efficient markets. A classic and time proven strategy is value investing. After the collapse of 07/08, bank stocks greatly fell, but all the other stocks fell with them. Some stocks worth $100 were selling for $50. Value investors quickly snapped up these stocks because they had a margin of safety. Even if the stock didn't go back to 100, it could go up to $80 or $90 eventually, and investors profit. The main ideas in value investing are: have a big margin of safety, look at a company's fundamentals (earnings, book value, etc), and see if it promises adequate return. Coke has tremendous earnings and it's a great company, but it's so large that you're never going to make 20% profits on it annually, because it just can't grow that fast. Another field of active investing is technical analysis. As opposed to the \"\"fundamental analysis\"\" of value investing, technical analysis involves looking at charts for patterns, and looking at stock history to determine future paths. Things like resistance points and trend lines also play a role. Technical analysts believe that stocks are just ticker symbols and that you can use guidelines to predict where they're headed. Another type of active investing is day trading. This basically involves buying and selling stocks every hour or every minute or just at a rapid pace. Day traders don't hold onto investments for very long, and are always trying to predict the market in the short term and take advantage of it. Many individual investors are also day traders. The other question is, how do you choose a strategy? The short answer is: pick whatever works for you. The long answer is: Day trading and technical analysis is a lot of luck. If there are consistent systems for trading , then people are keeping them secret, because there is no book that you can read and become a consistent trader. High frequency trading (HFT) is an area where people basically mint money, but it s more technology and less actual investing, and would not be categorized as day trading. Benjamin Graham once said: In the short run, the market is a voting machine but in the long run it is a weighing machine. Value investing will work because there's evidence for it throughout history, but you need a certain temperament for it and most people don't have that. Furthermore, it takes a lot of time to adequately study stocks, and people with day jobs can't devote that kind of time. So there you have it. This is my opinion and by no means definitive, but I hope you have a starting point to continue your study. I included the theory in the beginning because there are too many monkeys on CNBC and the news who just don't understand fundamental economics and finance, and there's no sense in applying a theory until you can understand why it works and when it doesn't.\"", "title": "" }, { "docid": "205685", "text": "In general, to someone in a similar circumstance I might suggest that the lowest-risk option is to immediately convert your excess currency into the currency you will be spending. Note that 'risk' here refers only to the variance in possible outcomes. By converting to EUR now (assuming you are moving to an EU country using the EUR), you eliminate the chance that the GBP will weaken. But you also eliminate the chance that the GBP will strengthen. Thus, you have reduced the variance in possible outcomes so that you have a 'known' amount of EUR. To put money in a different currency than what you will be using is a form of investing, and it is one that can be considered high risk. Invest in a UK company while you plan on staying in the UK, and you take on the risk of stock ownership only. But invest in a German company while you plan on staying in the UK, you take on the risk of stock ownership + the risk of currency volatility. If you are prepared for this type of risk and understand it, you may want to take on this type of risk - but you really must understand what you're getting into before you do this. For most people, I think it's fair to say that fx investing is more accurately called gambling [See more comments on the risk of fx trading here: https://money.stackexchange.com/a/76482/44232]. However, this risk reduction only truly applies if you are certain that you will be moving to an EUR country. If you invest in EUR but then move to the US, you have not 'solved' your currency volatility problem, you have simply replaced your GBP risk with EUR risk. If you had your plane ticket in hand and nothing could stop you, then you know what your currency needs will be in 2 years. But if you have any doubt, then exchanging currency now may not be reducing your risk at all. What if you exchange for EUR today, and in a year you decide (for all the various reasons that circumstances in life may change) that you will stay in the UK after all. And during that time, what if the GBP strengthened again? You will have taken on risk unnecessarily. So, if you lack full confidence in your move, you may want to avoid fully trading your GBP today. Perhaps you could put away some amount every month into EUR (if you plan on moving to an EUR country), and leave some/most in GBP. This would not fully eliminate your currency risk if you move, but it would also not fully expose yourself to risk if you end up not moving. Just remember that doing this is not a guarantee that the EUR will strengthen and the GBP will weaken.", "title": "" }, { "docid": "285560", "text": "\"If I invest in index funds or other long term stocks that pay dividend which I reinvest, they don't need to be worth more per share for me to make a profit, right? That is, if I sell part of the stocks, it's GOOD if they're worth more than I bought them at, but the real money comes from the QUANTITY of stocks that you get by reinvesting your dividends, right? I would say it is more the other way around. It is nice to get dividends and reinvest them, but overall the main gain comes from the stocks going up in value. The idea with index funds, however, is that you don't rely on any particular stock going up in value; instead you just rely on the aggregate of all the funds in the index going up. By buying lots of stocks bundled in an index fund, you avoid being too reliant on any one company's performance. Can I invest \"\"small amounts\"\" (part of paycheck) into index funds on a monthly basis, like €500, without taking major \"\"transaction fees\"\"? (Likely to be index fund specific... general answers or specific answers using popular stocks welcomed). Yes, you can. At least in the US, whether you can do this automatically from your paycheck depends on whether you employer has that set up. I don't know that work in the Netherlands. However, at the least, you can almost certainly set up an auto-invest program that takes $X out of your bank account every month and buys shares of some index fund(s). Is this plan market-crash proof? My parents keep saying that \"\"Look at 2008 and think about what such a thing would do to your plan\"\", and I just see that it will be a setback, but ultimately irrelevant, unless it happens when I need the money. And even then I'm wondering whether I'll really need ALL of my money in one go. Doesn't the index fund go back up eventually? Does a crash even matter if you plan on holding stocks for 10 or more years? Crashes always matter, because as you say, there's always the possibility that the crash will occur at a time you need the money. In general, it is historically true that the market recovers after crashes, so yes, if you have the financial and psychological fortitude to not pull your money out during the crash, and to ride it out, your net worth will probably go back up after a rough interlude. No one can predict the future, so it's possible for some unprecedented crisis to cause an unprecedented crash. However, the interconnectedness of stock markets and financial systems around the world is now so great that, were such a no-return crash to occur, it would probably be accompanied by the total collapse of the whole economic system. In other words, if the stock market dies suddenly once and for all, the entire way of life of \"\"developed countries\"\" will probably die with it. As long as you live in such a society, you can't really avoid \"\"gambling\"\" that it will continue to exist, so gambling on there not being a cataclysmic market crash isn't much more of a gamble. Does what I'm planning have similarities with some financial concept or product (to allow me to research better by looking at the risks of that concept/product)? Maybe like a mortgage investment plan without the bank eating your money in between? I'm not sure what you mean by \"\"what you're planning\"\". The main financial products relevant to what you're describing are index funds (which you already mentioned) and index ETFs (which are basically similar with regard to the questions you're asking here). As far as concepts, the philosophy of buying low-fee index funds, holding them for a long time, and not selling during crashes, is essentially that espoused by Jack Bogle (not quite the inventor of the index fund, but more or less its spiritual father) and the community of \"\"Bogleheads\"\" that has formed around his ideas. There is a Bogleheads wiki with lots of information about the details of this approach to investing. If this strategy appeals to you, you may find it useful to read through some of the pages on that site.\"", "title": "" }, { "docid": "98920", "text": "What you're getting at is the same as investing with leverage. Usually this comes in the form in a margin account, which an investor uses to borrow money at a low interest rate, invest the money, and (hopefully!) beat the interest rate. is this approach unwise? That completely depends on how your investments perform and how high your loan's interest rate is. The higher your loan's interest rate, the more risky your investments will have to be in order to beat the interest rate. If you can get a return which beats the interest rates of your loan then congratulations! You have come out ahead and made a profit. If you can keep it up you should make the minimum payment on your loan to maximize the amount of capital you can invest. If not, then it would be better to just use your extra cash to pay down the loan. [are] there really are investments (aside from stocks and such) that I can try to use to my advantage? With interest rates as low as they are right now (at least in the US) you'll probably be hard-pressed to find a savings account or CD that will return a higher interest rate than your loan's. If you're nervous about the risk associated with investing in stocks and bonds (as is healthy!), then know that they come in a wide spectrum of risk. It's up to you to evaluate how much risk you're willing to take on to achieve a higher return.", "title": "" }, { "docid": "483123", "text": "\"The question is: how do you quantify investment risk? As Michael S says, one approach is to treat investment returns as a random variable. Bill Goetzmann (Yale finance professor) told me that if you accept that markets are efficient or that the price of an asset reflects it's underlying value, then changes in price represent changes in value, so standard deviation naturally becomes the appropriate measure for riskiness of an asset. Essentially, the more volatile an asset, the riskier it is. There is another school of thought that comes from Ben Graham and Warren Buffett, which says that volatility is not inherently risky. Rather, risk should be defined as the permanent loss of capital, so the riskiness of an asset is the probability of a permanent loss of capital invested. This is easy to do in casino games, based on basic probability such as roulette or slots. But what has been done with the various kinds of investment risks? My point is saying that certain bonds are \"\"low risk\"\" isn't good enough; I'd like some numbers--or at least a range of numbers--and therefore one could calculate expected payoff (in the statistics sense). Or can it not be done--and if not, why not? Investing is more art than science. In theory, a Triple-A bond rating means the asset is riskless or nearly riskless, but we saw that this was obviously wrong since several of the AAA mortgage backed securities (MBS) went under prior to the recent US recession. More recently, the current threat of default suggests that bond ratings are not entirely accurate, since US Treasuries are considered riskless assets. Investors often use bond ratings to evaluate investments - a bond is considered investment grade if it's BBB- or higher. To adequately price bonds and evaluate risk, there are too many factors to simply refer to a chart because things like the issuer, credit quality, liquidity risk, systematic risk, and unsystematic risk all play a factor. Another factor you have to consider is the overall portfolio. Markowitz showed that adding a riskier asset can actually lower the overall risk of a portfolio because of diversification. This is all under the assumption that risk = variance, which I think is bunk. I'm aware that Wall Street is nothing like roulette, but then again there must be some math and heavy economics behind calculating risk for individual investors. This is, after all, what \"\"quants\"\" are paid to do, in part. Is it all voodoo? I suspect some of it is, but not all of it. Quants are often involved in high frequency trading as well, but that's another note. There are complicated risk management products, such as the Aladdin system by BlackRock, which incorporate modern portfolio theory (Markowitz, Fama, Sharpe, Samuelson, etc) and financial formulas to manage risk. Crouhy's Risk Management covers some of the concepts applied. I also tend to think that when people point to the last x number of years of stock market performance, that is of less value than they expect. Even going back to 1900 provides \"\"only\"\" 110 years of data, and in my view, complex systems need more data than those 40,500 data points. 10,000 years' worth of data, ok, but not 110. Any books or articles that address these issues, or your own informed views, would be helfpul. I fully agree with you here. A lot of work is done in the Santa Fe Institute to study \"\"complex adaptive systems,\"\" and we don't have any big, clear theory as of yet. Conventional risk management is based on the ideas of modern portfolio theory, but a lot of that is seen to be wrong. Behavioral finance is introducing new ideas on how investors behave and why the old models are wrong, which is why I cannot suggest you study risk management and risk models because I and many skilled investors consider them to be largely wrong. There are many good books on investing, the best of which is Benjamin Graham's The Intelligent Investor. Although not a book on risk solely, it provides a different viewpoint on how to invest and covers how to protect investments via a \"\"Margin of Safety.\"\" Lastly, I'd recommend Against the Gods by Peter Bernstein, which covers the history of risk and risk analysis. It's not solely a finance book but rather a fascinating historical view of risk, and it helps but many things in context. Hope it helps!\"", "title": "" }, { "docid": "592661", "text": "Google 'information ratio'. It is better suited to what you want than the Sharpe or Sortino ratios because it only evaluates the excess return you get from your investment, ie. return from your investment minus the return from a benchmark investment. The benchmark here could be an index like the S&P500.", "title": "" }, { "docid": "549270", "text": "For most people, you don't want individual bonds. Unless you are investing very significant amounts of money, you are best off with bond funds (or ETFs). Here in Canada, I chose TDB909, a mutual fund which seeks to roughly track the DEX Universe Bond index. See the Canadian Couch Potato's recommended funds. Now, you live in the U.S. so would most likely want to look at a similar bond fund tracking U.S. bonds. You won't care much about Canadian bonds. In fact, you probably don't want to consider foreign bonds at all, due to currency risk. Most recommendations say you want to stick to your home country for your bond investments. Some people suggest investing in junk bonds, as these are likely to pay a higher rate of return, though with an increased risk of default. You could also do fancy stuff with bond maturities, too. But in general, if you are just looking at an 80/20 split, if you are just looking for fairly simple investments, you really shouldn't. Go for a bond fund that just mirrors a big, low-risk bond index in your home country. I mean, that's the implication when someone recommends a 60/40 split or an 80/20 split. Should you go with a bond mutual fund or with a bond ETF? That's a separate question, and the answer will likely be the same as for stock mutual funds vs stock ETFs, so I'll mostly ignore the question and just say stick with mutual funds unless you are investing at least $50,000 in bonds.", "title": "" }, { "docid": "317533", "text": "\"You are your own worst enemy when it comes to investing. You might think that you can handle a lot of risk but when the market plummets you don't know exactly how you'll react. Many people panic and sell at the worst possible time, and that kills their returns. Will that be you? It's impossible to tell until it happens. Don't just invest in stocks. Put some of your money in bonds. For example TIPS, which are inflation adjusted treasury bonds (very safe, and the return is tied to the rate of inflation). That way, when the stock market falls, you'll have a back-stop and you'll be less likely to sell at the wrong time. A 50/50 stock/bond mix is probably reasonable. Some recommend your age in bonds, which for you means 20% or so. Personally I think 50/50 is better even at your young age. Invest in broad market indexes, such as the S&P 500. Steer clear of individual stocks except for maybe 5-10% of your total. Individual stocks carry the risk of going out of business, such as Enron. Follow Warren Buffet's two rules of investing: a) Don't lose money b) See rule a). Ignore the \"\"investment porn\"\" that is all around you in the form of TV shows and ads. Don't chase hot companies, sectors or countries. Try to estimate what you'll need for retirement (if that's what your investing for) and don't take more risk than you need to. Try to maintain a very simple portfolio that you'll be able to sleep well with. For example, check into the coffeehouse investor Pay a visit to the Bogleheads Forum - you can ask for advice there and the advice will be excellent. Avoid investments with high fees. Get advice from a good fee-only investment advisor if needed. Don't forget to enjoy some of your money now as well. You might not make it to retirement. Read, read, read about investing and retirement. There are many excellent books out there, many of which you can pick up used (cheap) through amazon.com.\"", "title": "" }, { "docid": "352557", "text": "Use a currency ETF. there are many. Specific to your question there is WisdomTree Dreyfus Brazilian Real Fund (BZF) I don't happen to find a currency ETF for Thailand, so the closest you could come to a Thai currency fund would be something that's an Index fund ETF that is based on an index in the Thai Market such as: MSCI Thailand Investable Market Index Fund Because that fund is investing in an index of stocks that trade on the Thai market, you are in effect investing in something denominated in Baht. This is spelled out in the prospectus where it discusses 'currency risk'. The problem is that you are however not investing in just the currency, but rather a broad index of stocks denominated in that currency. Still to the extent the market holds fairly steady, you get much the same effect of investing in just the currency. to the extent the market is moving, you get the net effect of what the thai market does, plus how the bhat trades relative to the dollar.", "title": "" }, { "docid": "8012", "text": "It is worth noting first that interest and short-term dividends/capital gains are all taxed at the same rate. So all the investments below I mention (even savings accounts) will be taxed at the same rate. Also, even short-term capital losses can often be harvested to reduce your tax rate in many countries. While it is worth paying attention to the taxes when investing in the short term the more important factor is how much risk that you can take or want to take with the money. Most equity portfolios like the S&P index give a much higher risk that there will be much less in the account when you need to buy. You generally have a higher expected return with equity but as you mention that return is very random over such a short period. Over such a short variable period many people will invest in short term bond-index funds or just keep the fund in a high-yielding savings account. With the savings account your money is guaranteed. Short term bond funds will have generally higher yields but a small chance you may lose money in the short term. Some people can trade short-term bond indices for free with their broker but if you can't be sure to include the trading costs when thinking about which investment to use as with how low yields are currently the fees may eat up any advantage you gain.", "title": "" } ]
PLAIN-1045	Dr. Benjamin Feingold	[ { "docid": "MED-5062", "text": "BACKGROUND: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. METHODS: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. FINDINGS: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. INTERPRETATION: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.", "title": "Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled..." }, { "docid": "MED-5063", "text": "Evidence supports a trial period of eliminating colourings and preservatives from the diet", "title": "Food additives and hyperactivity" } ]	[ { "docid": "MED-3380", "text": "Attention deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in children. Symptoms of ADHD include hyperactivity, low frustration tolerance, impulsivity, and inattention. While the biological pathways leading to ADHD are not clearly delineated, a number of genetic and environmental risk factors for the disorder are recognized. In the early 1970s, research conducted by Dr. Benjamin Feingold found that when hyperactive children were given a diet free of artificial food additives and dyes, symptoms of hyperactivity were reduced. While some clinical studies supported these findings, more rigorous empirical studies conducted over the next 20 years were less positive. As a result, research on the role of food additives in contributing to ADHD waned. In recent years, however, interest in this area has revived. In response to more recent research and public petitions, in December 2009 the British government requested that food manufacturers remove most artificial food dyes from their products. While these strictures could have positive effects on behavior, the removal of food dyes is not a panacea for ADHD, which is a multifaceted disorder with both biological and environmental underpinnings. © 2011 International Life Sciences Institute.", "title": "Artificial food dyes and attention deficit hyperactivity disorder." }, { "docid": "MED-1712", "text": "Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.", "title": "Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici..." }, { "docid": "MED-2510", "text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.", "title": "Comparative and meta-analytic insights into life extension via dietary restriction." }, { "docid": "MED-1021", "text": "CONTEXT: Diabetic retinopathy (DR) is the leading cause of blindness in the working-aged population in the United States. There are many new interventions for DR, but evidence to support their use is uncertain. OBJECTIVE: To review the best evidence for primary and secondary intervention in the management of DR, including diabetic macular edema. EVIDENCE ACQUISITION: Systematic review of all English-language articles, retrieved using a keyword search of MEDLINE (1966 through May 2007), EMBASE, Cochrane Collaboration, the Association for Research in Vision and Ophthalmology database, and the National Institutes of Health Clinical Trials Database, and followed by manual searches of reference lists of selected major review articles. All English-language randomized controlled trials (RCTs) with more than 12 months of follow-up and meta-analyses were included. Delphi consensus criteria were used to identify well-conducted studies. EVIDENCE SYNTHESIS: Forty-four studies (including 3 meta-analyses) met the inclusion criteria. Tight glycemic and blood pressure control reduces the incidence and progression of DR. Pan-retinal laser photocoagulation reduces the risk of moderate and severe visual loss by 50% in patients with severe nonproliferative and proliferative retinopathy. Focal laser photocoagulation reduces the risk of moderate visual loss by 50% to 70% in eyes with macular edema. Early vitrectomy improves visual recovery in patients with proliferative retinopathy and severe vitreous hemorrhage. Intravitreal injections of steroids may be considered in eyes with persistent loss of vision when conventional treatment has failed. There is insufficient evidence for the efficacy or safety of lipid-lowering therapy, medical interventions, or antivascular endothelial growth factors on the incidence or progression of DR. CONCLUSIONS: Tight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR. Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments.", "title": "Management of diabetic retinopathy: a systematic review." }, { "docid": "MED-2498", "text": "Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.", "title": "Dietary Restriction, Growth Factors and Aging: from yeast to humans" }, { "docid": "MED-3283", "text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.", "title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..." }, { "docid": "MED-2324", "text": "The level of food restriction that results in life extension and retarded aging in rodents also enhances their ability to cope with intense stressors. Moreover, this level of dietary restriction (DR) leads to a modest increase in the daily peak concentration of plasma free corticosterone, which strongly points to DR as a low-intensity stressor. These findings suggest that hormesis plays a role in the life-extending and anti-aging actions of DR. The evidence for and against this possibility is considered, and it is concluded that hormesis does have an important role.", "title": "The role of hormesis in life extension by dietary restriction." }, { "docid": "MED-2509", "text": "DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.", "title": "Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR" }, { "docid": "MED-2502", "text": "Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.", "title": "Macronutrient balance and lifespan" }, { "docid": "MED-2603", "text": "FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.", "title": "FADD: a regulator of life and death." }, { "docid": "MED-3381", "text": "Background: The proposition that synthetic food colors can induce adverse behavioral effects in children was first enunciated in 1975 by Feingold [Why Your Child Is Hyperactive. New York:Random House (1975)], who asserted that elevated sensitivity to food additives underlies the signs of hyperactivity observed in some children. Although the evidence suggested that some unknown proportion of children did respond to synthetic food colors, the U.S. Food and Drug Administration (FDA) interpreted the evidence as inconclusive. A study published in 2007 [McCann et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 370:1560–1567 (2007)] drew renewed attention to the hypothesis because of the study’s size and scope. It led the FDA to review the evidence, hold a public hearing, and seek the advice of its Food Advisory Committee. In preparation for the hearing, the FDA reviewed the available evidence and concluded that it did not warrant further agency action. Objectives: In this commentary I examine the basis of the FDA’s position, the elements of the review that led to its decision and that of the Food Advisory Committee, and the reasons that this is an environmental health issue. Discussion: The FDA review confined itself, in essence, to the clinical diagnosis of hyperactivity, as did the charge to the committee, rather than asking the broader environmental question of behavioral effects in the general population; it failed to recognize the significance of vulnerable subpopulations; and it misinterpreted the meaning of effect size as a criterion of risk. The FDA’s response would have benefited from adopting the viewpoints and perspectives common to environmental health research. At the same time, the food color debate offers a lesson to environmental health researchers; namely, too narrow a focus on a single outcome or criterion can be misleading.", "title": "Synthetic Food Colors and Neurobehavioral Hazards: The View from Environmental Health Research" }, { "docid": "MED-1116", "text": "Molecular mimicry is one of the pathological mechanisms proposed to explain the association between microorganisms and autoimmune diseases. This review deals with the association between bacteria and rheumatic diseases with a special emphasis on rheumatoid arthritis where upper urinary tract infection by Proteus mirabilis is the possible cause of this severe, arthritic condition. Prospective trials involving anti-Proteus therapy should be carried out.", "title": "Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity." }, { "docid": "MED-2763", "text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.", "title": "Facing the facelessness of public health: what's the public got to do with it?" }, { "docid": "MED-1709", "text": "In the preceding point narrative, Drs. Bray and Popkin provide their opinion and review data that suggest to them that we need to reconsider the consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative below, we argue that there is no clear or convincing evidence that any dietary or added sugar has a unique or detrimental impact relative to any other source of calories on the development of obesity or diabetes. Sugar is purely a highly palatable source of energy; because it has no other property that appears to contribute to our nutritional well-being, it is not an essential food for most of us. For those who wish to reduce energy consumption, ingesting less sugar is a good place to start. However, doing so does not automatically portend any clinical benefit.", "title": "Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: we have, but the pox on sugar is overwrought and ..." }, { "docid": "MED-2820", "text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.", "title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis" }, { "docid": "MED-1707", "text": "Sugar-sweetened drinks have been associated with several health problems. In the point narrative as presented below, we provide our opinion and review of the data to date that we need to reconsider consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative following our contribution, Drs. Kahn and Sievenpiper provide a defense and suggest that dietary sugar is not the culprit. Data from the National Health and Nutrition Examination Survey and U.S. Department of Agriculture dietary surveys along with commercial Homescan data on household purchases were used to understand changes in sugar and fructose consumption. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. About 75% of all foods and beverages contain added sugar in a large array of forms. Consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease. Drinking two 16-ounce SSBs per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized controlled trials in children and adults lasting 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Recent studies suggest a gene-SSB potential relationship. Consumption of calorie-sweetened beverages has continued to increase and plays a role in the epidemic of obesity, the metabolic syndrome, and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain.", "title": "Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: health be damned! Pour on the sugar." }, { "docid": "MED-2812", "text": "Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Molecular mechanisms of curcumin action: gene expression." }, { "docid": "MED-1711", "text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.", "title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer" }, { "docid": "MED-4909", "text": "Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of ~ 1 gm cheese containing 1.5 or 3% basic SALP resulted in oral Al bioavailability (F) of ~ 0.1 and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8 to 9 h. These Al bioavailability results were intermediate to previously reported results from drinking water (F ~ 0.3%) and acidic-SALP incorporated into a biscuit (F ~ 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human’s daily Al intake (~ 95 and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.", "title": "Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese" }, { "docid": "MED-1181", "text": "Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.", "title": "Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses" }, { "docid": "MED-3844", "text": "Low lignan status has been reported to be related to an elevated risk of breast cancer. Since lignan status is reduced by antibacterial medications, it is plausible to hypothesize that repeated use of antibiotics may also be a risk factor for breast cancer. History of treatment for urinary tract infection was studied for its prediction of breast cancer among 9461 Finnish women 19–89 years of age and initially cancer-free. During a follow-up in 1973–1991, a total of 157 breast cancer cases were diagnosed. Women reporting previous or present medication for urinary tract infection at baseline showed an elevated breast cancer risk in comparison with other women. The age-adjusted relative risk was 1.34 (95% confidence interval (CI) = 0.98–1.83). The association was concentrated to women under 50 years of age. The relative risk for these women was 1.74 (95% CI 1.13–2.68), whereas it was 0.97 (95% CI 0.59–1.58) for older women. The relative risk in the younger age-group was 1.47 (95% CI 0.73–2.97) during the first 10 years of follow-up, and 1.93 (95% CI 1.11–3.37) for follow-up times longer than 10 years. These data suggest that premenopausal women using long-term medication for urinary tract infections show a possible elevated risk of future breast cancer. The results are, however, still inconclusive and the hypothesis needs to be tested by other studies. © 2000 Cancer ResearchCampaign", "title": "Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?" }, { "docid": "MED-3656", "text": "The etiology of bacterial vaginosis is unknown, and there are no long-term therapies for preventing this frequently recurring condition. Vaginal douching has been reported to be associated with bacterial vaginosis in observational studies. However, this association may be due to confounding by indication—that is, confounding by women douching in response to vaginal symptoms associated with bacterial vaginosis. The authors used marginal structural modeling to estimate the causal effect of douching on bacterial vaginosis risk while controlling for this confounding effect. In 1999–2002, nonpregnant women (n = 3,620) were recruited into a prospective study when they visited one of 12 public health clinics in Birmingham, Alabama, for routine care. Participants were assessed quarterly for 1 year. Bacterial vaginosis was based on a Nugent's Gram stain score of 7 or higher. Thirty-two percent of participants douched in every study interval, and 43.0% never douched. Of the 12,349 study visits, 40.2% were classified as involving bacterial vaginosis. The relative risk for regular douching as compared with no douching was 1.21 (95% confidence interval: 1.08, 1.38). These findings indicate that douching confers increased risk of disruption of vaginal flora. In the absence of a large randomized trial, these findings provide the best evidence to date for a risk of bacterial vaginosis associated with douching.", "title": "A Longitudinal Study of Vaginal Douching and Bacterial Vaginosis—A Marginal Structural Modeling Analysis" }, { "docid": "MED-4609", "text": "Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.", "title": "The beriberi analogy to myocardial infarction." }, { "docid": "MED-851", "text": "Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Chemoprevention in Barrett's oesophagus." }, { "docid": "MED-1500", "text": "BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.", "title": "Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies." }, { "docid": "MED-3549", "text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.", "title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention." }, { "docid": "MED-5209", "text": "A 5-year-old boy with autism developed dry eye and xerophthalmia. Serum vitamin A was undetectable. Dietary history revealed a markedly altered intake consisting of only fried potatoes and rice balls for 2 years. Fried potatoes contain no vitamin A. Autism is a multifaceted developmental disorder infrequently accompanied by abnormal eating practices. To the authors' knowledge, most children with autism who develop dietary vitamin A deficiency have consumed an excess of fried potatoes. Attention to possible vitamin A deficiency is essential when fried potatoes are consumed exclusively.", "title": "Fried-potato diet causes vitamin A deficiency in an autistic child." }, { "docid": "MED-5045", "text": "Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.", "title": "Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells" }, { "docid": "MED-5161", "text": "Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990, 1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHD. However, a weak risk reduction for CHD death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk.", "title": "Dietary intakes of flavonols and flavones and coronary heart disease in US women." }, { "docid": "MED-3978", "text": "SUMMARY The aim of this study was to investigate the relationship between dog and cat ownership and gastroenteritis in young children. A diary study of 965 children aged 4–6 years living in rural or semi-rural South Australia was undertaken. Data were collected on pet ownership, drinking water and other risk factors for gastroenteritis. Overall 89% of households had pets and dog ownership was more common than cat ownership. The multivariable models for gastroenteritis and pet ownership indicated that living in a household with a dog or cat was associated with a reduced risk of gastroenteritis (adj. OR 0·71, 95% CI 0·55–0·92; OR 0·70, % CI 0·51–0·97 respectively). This paper adds to the evidence that pets are not a major source of gastroenteritis in the home and lends support to the health benefits of pet ownership. However, this must be weighed against the potential negative consequences, such as dog bites, particularly for this age group.", "title": "Does dog or cat ownership lead to increased gastroenteritis in young children in South Australia?" } ]
5ab7e4745542993667794036	What is similar of Shatranj and 18XX?	[ { "docid": "739675", "text": "18XX is the generic term for a series of board games that, with a few exceptions, recreate the building of railroad corporations during the 19th century; individual games within the series use particular years in the 19th century as their title (usually the date of the start of railway development in the area of the world they cover), or \"18\" plus a two-letter geographical designator (such as \"18EU\" for a game set in the European Union). The games \"2038\", set in the future, and \"Poseidon\" and \"Ur, 1830 BC\", both set in ancient history, are also regarded as 18XX titles as their game mechanics and titling nomenclature are similar despite variance from the common railroad/stock-market theme.", "title": "" }, { "docid": "76267", "text": "Shatranj (Hindi शतरंज , Urdu شطرنج , from Middle Persian \"chatrang چترنگ\"), is an old form of chess, which came to the Western world by the Persians and later Greeks, and ultimately from India (\"chaturaṅga)\" via the Persian Empire. Modern chess gradually developed from this game.", "title": "" } ]	[ { "docid": "5018924", "text": "\"Shatranj Ke Khiladi\" (\"The Chess Player\"s) is a 1924 Hindi short-story written by Munshi Premchand. Premchand also made the Urdu version titled \"Shatranj ki bazi\".", "title": "" }, { "docid": "48335641", "text": "Shatranj Ke Mohre is a 1974 Hindi film starring Neetu Singh in the lead role.", "title": "" }, { "docid": "4864470", "text": "1830: The Game of Railroads and Robber Barons is a railroad operations and share trading board game first published by Avalon Hill in 1986 based on an original design by Francis Tresham. The popularity of \"1830\" spawned an industry creating similar \"\"18XX\"\" games. \"1830\" was republished in 2011 through a partnership of Mayfair Games and Lookout Games.", "title": "" }, { "docid": "30033566", "text": "Jeevan Ki Shatranj is a 1993 Hindi-language Indian feature film directed by S. A. Chandrasekhar, starring Mithun Chakraborty, Shilpa Shirodkar, Farha Naaz and Charan Raj", "title": "" }, { "docid": "52179010", "text": "Shatranj (\"Chess\") is a 1969 Indian Hindi-language spy thriller film co-produced and directed by S. S. Vasan. It stars Rajendra Kumar, Waheeda Rehman, Mehmood, Shashikala, Helen, Achala Sachdev and Agha.", "title": "" }, { "docid": "5016748", "text": "1829 (South) is a railroad operations and share-trading board game in the \"18xx\" series, first published by Hartland Trefoil Ltd (UK) in 1974 from an original design by Francis Tresham, but is now out of print. \"1829 (South)\" is based on railroading in southern England and Wales and became the first game in the \"18xx\" series, with the basic game design now licensed to companies such as Mayfair Games and Hans im Glück. The game is also the inspiration for Sid Meier's \"Railroad Tycoon\" series.", "title": "" }, { "docid": "30033656", "text": "Shatranj (English: \"Chess\" ) is a 1993 Indian Hindi-language film directed by Aziz Sejawal, starring Mithun Chakraborty, Jackie Shroff, Kader Khan, Juhi Chawla and Divya Bharti in her last film appearance. Kader Khan's son Sarfaraz Khan appeared as the younger version of his character. The film was box office hit.", "title": "" }, { "docid": "1346542", "text": "Tamerlane Chess is a strategy board game related to chess and derived from chaturanga. It was developed in Persia during the reign of Timur, also called Tamerlane (1336–1405). Some sources attribute the game's invention to Timur (Timur's Chess), but this is by no means certain. Because Tamerlane Chess is a larger variant of chaturanga, it is also called \"Shatranj Kamil\" (Perfect Chess) or \"Shatranj Al-Kabir\" (Large Chess or Great Chess). It is distinctive in that there are varieties of pawn, each of which promotes in its own way.", "title": "" }, { "docid": "5078459", "text": "William R. \"Bill\" Dixon is an American board game designer, who has four 18XX games published:", "title": "" }, { "docid": "21888466", "text": "Shatar (Mongolian: ᠮᠣᠩᠭᠣᠯ ᠰᠢᠲᠠᠷ᠎ᠠ \"Monggol sitar-a\", \"Mongolian shatranj\"; a.k.a. shatar) and hiashatar are two chess variants played in Mongolia.", "title": "" }, { "docid": "13341129", "text": "What It Is is a slang phrase popularized in the 1970s as a greeting or as another way to ask an individual about their well-being or general perception of things (similar to \"How are you?\", \"How is it going?\" or \"What's Up?\") It is a shortening of the greeting, \"What it is, what it was, and what it shall be,\" popular in the 1960s among African Americans.", "title": "" }, { "docid": "180851", "text": "The exact location, time and method of the entry of chess, or rather its immediate precursor Shatranj, into western Europe is unknown, however linguistic evidence suggest that it was almost certainly transmitted via the Arab world.", "title": "" }, { "docid": "33852562", "text": "Norm Potter (18xx–1951) was an Australian professional rugby league footballer of the 1910s and 1920s . A Queensland state and Australia national representative front-row forward, he was one of Queensland's early stalwart star players making forty-four state appearances in an unbroken representative career between 1918 and 1927.", "title": "" }, { "docid": "24694", "text": "Philosophy of law is a branch of philosophy and jurisprudence that seeks to answer basic questions about law and legal systems, such as \"What is law?\", \"What are the criteria for legal validity?\", \"What is the relationship between law and morality?\", and many other similar questions.", "title": "" }, { "docid": "1449955", "text": "Maharajah and the Sepoys, originally called Shatranj Diwana Shah and also known as The Mad King's Game and Maharajah chess, is a popular chess variant with different armies for white and black. It was first played in the 19th century in India. It is a solved game with forced win for Black.", "title": "" }, { "docid": "1488363", "text": "The asor (Hebrew: עָשׂוֹר‎ ‎ \"ʿasor\"; from עשר \"eśer\", meaning \"ten\") was a musical instrument \"of ten strings\" mentioned in the Bible. There is little agreement on what sort of instrument it was or to what instruments it had similarities.", "title": "" }, { "docid": "15987387", "text": "William Cooper Nell (December 16, 1816 – May 25, 1874) was an African-American abolitionist, journalist, publisher, author, and civil servant of Boston, Massachusetts, who worked for integration of schools and public facilities in the state. Writing for abolitionist newspapers \"The Liberator\" and \"The North Star\", he helped publicize the anti-slavery cause. He published the \"North Star\" from 1847 to 18xx, moving temporarily to Rochester, New York.", "title": "" }, { "docid": "53897361", "text": "Henry Lawrence Southwick (18xx- January 1932) was the third president of Emerson College of Oratory (now Emerson College), located in the Back Bay, Boston, MA. In addition to teaching at the college, he was a noted international performer of Shakespeare. With his wife, Jessie Eldridge Southwick, he created and directed The Southwick Recital Series, looked forward to by contemporary literary audiences of Boston and continues as an Emerson College event, today.", "title": "" }, { "docid": "11524605", "text": "Saswati Sen (Hindi: शाश्वती सेन) is a leading Indian exponent of Kathak, an Indian classical dance form. She is a senior disciple of Pandit Birju Maharaj. She achieved early fame by dancing in Satyajit Ray's film, \"Shatranj Ke Khilari\" (1977), his invocation of Lucknow society at its \"Paris of India\" zenith.", "title": "" }, { "docid": "39836483", "text": "Codec Acceleration describes computer hardware that offloads the computationally intensive compression or decompression. This allows, for instance, a mobile phone to decode what would generally be a very difficult, and expensive video to decode it with no stuttering, and using less battery life than un-accelerated decoding would have taken, and similar acceleration is used on a broad variety of other appliances and computers for similar reasons. What could take a general purpose processor 100 Watts to decode on a general purpose processor, could take 10W on a general purpose GPU, and even less on a dedicated hardware CODEC.", "title": "" }, { "docid": "27739", "text": "Shogi (将棋 , shōgi ) ( , ] or ] ), also known as Japanese chess or the Generals' Game, is a two-player strategy board game in the same family as Western (international) chess, chaturanga, makruk, shatranj, janggi and xiangqi, and is the most popular of a family of chess variants native to Japan. \"Shōgi\" means general's (\"shō\" 将 ) board game (\"gi\" 棋 ).", "title": "" }, { "docid": "815983", "text": "¡Qué Locura! is a hidden camera-comedy television show from Venezuela. In English, \"¡Qué Locura!\" translates as \"What Madness!\" or \"What Insanity!\". The premise of the show involves concealed cameras filming pranks on celebrities, both local and international. It is similar to Punk'd on MTV in the United States.", "title": "" }, { "docid": "39695496", "text": "What We Almost Made is a 2008 mixtape by London-born entertainer Example. Similar to his previous full-length releases \"We Didn't Invent the Remix\" and \"What We Made\", all of the songs in \"What We Almost Made\" were mainly written by Example and produced by Rusher. As the title suggests, \"What We Almost Made\" was made as a follow-up to \"What We Made\" and contains unreleased tracks that weren't included in any of his previous releases (five of which feature various artists); three of the songs, although, were originally B-sides taken from the vinyl releases of the singles \"I Don't Want To\", \"So Many Roads\" and \"Me & Mandy\" (tracks 15, 5 and 6, respectively).", "title": "" }, { "docid": "29265700", "text": "The 26th Filmfare Awards were held in 1979. Raj Khosla's Main Tulsi Tere Aangan Ki was named the Best Film of the Year. Amitabh Bachchan won his second consecutive Best Actor Award for his double role in Don. Satyajit Ray won his sole Best Director Award for Shatranj Ke Khiladi.", "title": "" }, { "docid": "37948583", "text": "Saeed Jaffrey OBE (Punjabi: ਸਈਦ ਜਾਫ਼ਰੀ, ; Hindi: सईदजाफ़री ) 1929 - 2015) was an Indian-born British actor, who worked in numerous British and Indian movies. His film credits include \"The Man Who Would Be King\" (1975), \"Shatranj Ke Khiladi\" (The Chess Players) (1977), \"Gandhi\" (1982). His brief filmography is given below.", "title": "" }, { "docid": "4364374", "text": "TUXIS was a boys’ program similar to the Scouting movement promoted by Canadian Protestant churches. There are a number of variations of what the acronym \"TUXIS\" is said to stand for. Most commonly, it is said to stand for \"'you' ('U') and 'I' in 'T'raining and 'S'ervice with Christ ('X') in the centre.\" Another similar meaning was \"Training Under Christ In Service\".", "title": "" }, { "docid": "39684665", "text": "What's the Future of Business?: Changing the Way Businesses Create Experiences is a marketing and business book by the speaker, digital analyst, and author Brian Solis. The book uses infographics and illustrations as well as text to diagnose the changing landscape of business and the role shared experience will play in a new age of consumerism. Solis studied UX to create what he calls an \"analog app,\" basing the book on a virtual slider that helps readers navigate the contents of the book similar to the way an app works.", "title": "" }, { "docid": "39002918", "text": "Rajanadai is a 1989 Tamil crime film directed by S. A. Chandrasekhar. The film features Vijayakanth, Gouthami, Vidhyashree and Seetha in lead roles. The film, produced by Shoba Chandrasekhar, had musical score by M. S. Viswanathan and was released on 28 October 1989. This movie did well in the box office at the time of its release. The film was later remade in Hindi as \"Jeevan Ki Shatranj\".", "title": "" }, { "docid": "39109684", "text": "\"For sale: baby shoes, never worn.\" is the entirety of what has been described as a six-word novel, making it an extreme example of what is called flash fiction or sudden fiction. Although it is often attributed to Ernest Hemingway, the link to him is unsubstantiated and similar stories predate him.", "title": "" }, { "docid": "12776125", "text": "Epistemology (from Greek \"ἐπιστήμη\" – \"episteme\"-, \"knowledge, science\" + \"λόγος\", \"logos\") or theory of knowledge is the branch of philosophy concerned with the nature and scope (limitations) of knowledge. It addresses the questions \"What is knowledge?\", \"How is knowledge acquired?\", \"What do people know?\", \"How do we know what we know?\", and \"Why do we know what we know?\". Much of the debate in this field has focused on analyzing the nature of knowledge and how it relates to similar notions such as truth, belief, and justification. It also deals with the means of production of knowledge, as well as skepticism about different knowledge claims.", "title": "" } ]
5a7b2e995542995eb53be8c4	Which company is ranked first in ketchup in the United States and is distributed through Sun Mark?	[ { "docid": "13881", "text": "The H. J. Heinz Company, or Heinz, was an American food processing company with world headquarters in Pittsburgh, Pennsylvania. It was founded by Henry John Heinz in 1869. The H. J. Heinz Company manufactures thousands of food products in plants on six continents, and markets these products in more than 200 countries and territories. The company claims to have 150 number-one or number-two brands worldwide. Heinz ranked first in ketchup in the US with a market share in excess of 50%; Ore-Ida label held 46% of the frozen potato sector in 2003.", "title": "" }, { "docid": "46746226", "text": "Sun Mark was founded in 1995 by Rami Ranger and operates from its head office in Greenford, Middlesex. Sun Mark, in partnership with its sister company Sea Air & Land Forwarding Ltd, was founded with the purpose to provide customers an end to end service for marketing and distribution of FMCG products. Sun Mark focuses on approaching traditionally hard to reach markets around the world and provides both its own label and leading brands such as Heinz, Mondelez, Nestle and Unilever amongst others to certain territories worldwide. Sun Mark is also a leading member of the Landmark Wholesale group.", "title": "" } ]	[ { "docid": "50787626", "text": "Fruit ketchup is a condiment prepared using fruit as a primary ingredient. Various fruits are used in its preparation, and it is also used as a spread and marinade, among other uses. Banana ketchup is a type of fruit ketchup that is common in the Philippines. Some companies mass-produce fruit ketchup, such as Philippines-based Jufran, and Chups, a small company based in Washington, D.C., United States.", "title": "" }, { "docid": "43787551", "text": "Mushroom ketchup is a style of ketchup (also spelled \"catsup\") that is prepared with mushrooms as its primary ingredient. Originally, ketchup in the United Kingdom was prepared with mushrooms as a primary ingredient, instead of tomato, the main ingredient in contemporary preparations of ketchup. Historical preparations involved packing whole mushrooms into containers with salt. It is used as a condiment and may be used as an ingredient in the preparation of other sauces and other condiments. Several brands of mushroom ketchup were produced and marketed in the United Kingdom, some of which were exported to the United States, and Geo Watkins Mushroom Ketchup continues to exist in contemporary times as a commercially mass-produced product.", "title": "" }, { "docid": "18640854", "text": "The Motion Picture Distributing and Sales Company was a major, national motion picture distribution company which operated in the United States between May 31, 1910 and the end of June, 1912. The company distributed almost 2,200 silent era motion pictures during its two-year existence. Its product came from the majority of independent American film producers, which hitherto had distributed their product through states' rights franchisees, as well as a handful of small, independent national distributors, all of whom opposed the attempted monopoly of distribution by the General Film Company, which was a subsidiary of Edison's Motion Picture Patents Company.", "title": "" }, { "docid": "1018286", "text": "Capri Sun ( or ) is a brand of juice concentrate drink owned by the German Company WILD and sold in laminated foil pouches. It was introduced in 1969 and named after the Italian island of Capri. Capri Sun has been distributed in the United States since 1981. Kraft Foods is a licensed production partner for North America. In the Netherlands, France, the UK, Belgium and Ireland, it is distributed by Coca-Cola Enterprises. In 2014 Capri-Sun entered the ever-growing Indian market through a joint venture with Hyderabad-based SDU Beverages to produce and market its fruit juices for kids. As of 2015, 5 flavors are certified kosher by OK Kosher Certification.", "title": "" }, { "docid": "41985151", "text": "AMCON Distributing Company is an American retail and wholesale consumer commodities sales and distribution company. Their wholesale products, which include processed and perishable foods, as well health care and tobacco products, are distributed to stores, supermarkets, and outlets primarily in the Rocky Mountains and southern regions of North America. The company operates two segments including wholesale distribution segment and retail segment. The company also operated sixteen retail health food stores in Florida and the Midwest. The company operates 4,500 convenience stores and 16,000 different products. In October 2012, it was ranked as the ninth largest convenience store distributor in the United States based on its annual sales.", "title": "" }, { "docid": "17907888", "text": "Saia is an American trucking company, or a less than truckload (LTL) trucking company, that originated in Houma, Louisiana in 1924. With original operation occurring in Louisiana and Texas for the first fifty years, expansion came after 1980 when coverage began reaching into more states within the South. Further expansion happened through merges with other companies, which allowed Saia to provide service for thirty six states. Saia ranks within the top ten of LTL carriers in the United States, yielding $1.3 billion in 2014.", "title": "" }, { "docid": "312139", "text": "The Gongman (also known as the \"man-with-the-gong\") is a company trademark for the Rank Organisation. It was used as the introduction to all Rank films, many of which were shot at their Pinewood Studios, and included those which Rank distributed. The Gongman logo was first used on films distributed by General Film Distributors, which was established in 1935 by the British producer C. M. Woolf and J. Arthur Rank; it was C.M. Woolf's secretary who devised the man-with-a-gong trademark. When the Rank Organisation was established in 1937, with General Film Distributors as one of its cornerstones, the logo was adopted for the whole organisation.", "title": "" }, { "docid": "182138", "text": "Sunoco is an American petroleum and petrochemical manufacturer headquartered in Newtown Square, Pennsylvania, United States, formerly known as Sun Company Inc. (1886–1920 and 1976–1998) and Sun Oil Co. (1920–1976). Sunoco is one of the largest gasoline distribution companies in the United States, with Sunoco brand gasoline being sold in over 4,700 outlets spanning 26 states, just over a third hosting convenience stores. Since 2012, Sunoco has been a wholly owned subsidiary of Energy Transfer Partners, based in Dallas, Texas.", "title": "" }, { "docid": "49073140", "text": "Graze is a United Kingdom-based snack company which offers over 200 snack combinations through snack subscription boxes, an online shop and retailers. The company distributes thousands of snack boxes per day across the UK. Graze expanded operations to include the United States in 2013, launching snacks into US retailers in 2016.", "title": "" }, { "docid": "52895376", "text": "LuLaRoe is a United States-based designer and seller of women's clothing that uses a multi-level marketing model to distribute products. LuLaRoe was founded in 2012 by Deanne Brady and her husband Mark Stidham, and is based in Corona, California. As a multi-level marketing company, LuLaRoe recruits independent distributors (referred to by the firm as \"fashion consultants\") to sell products directly, often through social media. LuLaRoe reported sales of approximately US$1 billion in 2016, which would have made it one of the largest firms in the multilevel marketing industry at the time, and by 2017 there were approximately 80,000 independent distributors selling the company's clothing.", "title": "" }, { "docid": "24265000", "text": "Entertainment Studios is an independent television production and distribution company that was founded by comedian Byron Allen in 1993 under the name CF Entertainment. The company produces and distributes first-run television series for U.S. television syndication. It also operates six digital cable and satellite channels, which broadcast a mix of original program content and syndicated programs that the company distributes for broadcast television through its Entertainment Studios Networks subsidiary. It produces and distributes films through the company's Freestyle Releasing film studio subsidiary and also owns The Grio, a news content provider catering to African-Americans.", "title": "" }, { "docid": "5887441", "text": "Core-Mark Holding Company (NASDAQ: CORE ) distributes fresh, chilled and frozen merchandise mainly to convenience stores in the United States. It also provides associated business services such as category management and management of promotions.", "title": "" }, { "docid": "20747930", "text": "Sun Pictures is a film distribution and production studio unit of Chennai based Sun Network owned by Kalanidhi Maran. Founded in 2000, it started producing the TV film \"Siragugal\" and distributing Tamil-language films, \"Kadhalil Vizhunthen\" being the first.", "title": "" }, { "docid": "10160028", "text": "Heinz Tomato Ketchup is a brand of ketchup produced by the H. J. Heinz Company (now Kraft-Heinz).", "title": "" }, { "docid": "43871868", "text": "Raminder Singh Ranger {'1': \", '2': \", '3': \", '4': \"} is the founder of Sun Mark, an international marketing and distribution company. He is also chairman and managing director of Sea Air and Land Forwarding Ltd.", "title": "" }, { "docid": "2377609", "text": "Aquila, Inc. was an electricity and natural gas distribution network headquartered in Kansas City, Missouri in the United States. The company also owned and operated power generation assets. It previously operated under the name UtiliCorp United, Inc. The company at one time ranked #33 on the Fortune 500 list.", "title": "" }, { "docid": "46296318", "text": "WDY was an AM radio station located in Roselle Park, New Jersey, that was licensed to the Radio Corporation of America (RCA) from September 19, 1921 to February 20, 1923, although its broadcasting career only spanned the period from December 15, 1921 through February 17, 1922. Despite being short-lived, WDY was the first broadcasting station licensed in the state of New Jersey, and one of the first in the United States. It also marked RCA's entrance into the broadcasting field, which the company would dominate in the U.S. for the next half century.", "title": "" }, { "docid": "7370148", "text": "Southern Company Gas, formerly AGL Resources, is an American Fortune 500 energy services holding company headquartered in Atlanta, Georgia. The company’s operations consist of natural gas distribution, wholesale services, retail operations, and midstream operations. Southern Company Gas is one of the largest natural gas distribution companies in the United States. The company serves 4.5 million utility customers through its regulated distribution subsidiaries across seven states. Southern Company Gas made the Fortune 500 list in 2015, Forbes 2000 in 2006, and is a member of the S&P 500 Index. In 2016, Southern Company bought out AGL and renamed it Southern Company Gas.", "title": "" }, { "docid": "33891817", "text": "Joseph Christopher Reyes (born 1953) is the co-chairman, with his brother Jude Reyes, of Reyes Holdings, a beer and food distribution holding company, ranked by \"Forbes\" magazine in 2012 as the 14th largest privately held company in the United States.", "title": "" }, { "docid": "39745817", "text": "The Mark 39 torpedo was the first homing torpedo in United States Navy service to use a trailing wire for mid-course guidance through the submarine's fire control system. The Mark 39 was a Mark 27 Mod 4 torpedo converted for development of wire guidance techniques, which were eventually incorporated into the Mark 37 Mod 1 and the Mark 45. Due to this development, the Mark 39 was considered obsolete and the remaining inventory was scrapped.", "title": "" }, { "docid": "1650148", "text": "Reser's Fine Foods, Inc., a United States corporation based in Beaverton, Oregon, manufactures and distributes fresh and frozen prepared foods. Over 1,000 products are available in the 50 U.S. states, Canada, Guam, Mexico, and areas of the Far East. Its prepared foods are sold in national grocery chains, independent outlets, and convenience stores. Oregon State University's football stadium, Reser Stadium, is named after the company, which is one of its sponsors. As of 2010, annual revenue was approximately $700 million, ranking Reser's as the sixth-largest private company in Oregon by revenue.", "title": "" }, { "docid": "14063145", "text": "Shin Kyung Sun (born 1933) is a Korean master of judo and a pioneer of that art in the United States of America. He is ranked 8th \"dan\" in judo, and also holds \"dan\" ranking in karate.", "title": "" }, { "docid": "11756851", "text": "Kyknos S.A. (Greek: Κύκνος meaning swan) is a Greek tomato company and it is one of the major tomato paste brands in the country. It is headquartered in Athens in the Athens Industrial Area west of downtown. It manufactures tomato paste, purée, ketchup and tomato sauces, which are used on pasta, lasagna and other cuisines. It also produces tomato pastes to North America including the United States in cities that have a Greek population. The company's claim to fame is its use of the Santorini cultivar of the cherry tomato, an intensely flavorful variety.", "title": "" }, { "docid": "55217395", "text": "This is a list of films released by the British distribution company General Film Distributors. GFD was part of the Rank Organisation, and handled films produced by the various companies controlled by or linked to Rank including Gainsborough Pictures, Two Cities Films and Ealing Studios. The list also includes films released by Rank's other distribution outlet Eagle-Lion Films. Foreign films which were handled in Britain by GFD, such as imports from the Hollywood studio Universal Pictures, are not included. In 1955 GFD was abolished and replaced by Rank Film Distributors.", "title": "" }, { "docid": "9458419", "text": "The Laconia Daily Sun is a five-day (Tuesday through Saturday) free morning daily newspaper published in the city of Laconia, New Hampshire, United States, covering Belknap County and the Lakes Region. Each publication day, 18,000 copies of the paper are distributed by bulk drops at more than 300 locations. Home delivery is available for a fee. The paper also publishes a free online edition.", "title": "" }, { "docid": "1665223", "text": "SunGard was an American multinational company based in Wayne, Pennsylvania, which provided software and services to education, financial services, and public sector organizations. It was formed in 1983, as a spin-off of the computer services division of Sun Oil Company. The name of the company originally was an acronym which stood for Sun Guaranteed Access to Recovered Data, a reference to the disaster recovery business it helped pioneer. SunGard was ranked at 480th in the U.S. Fortune 500 list in the year 2012.", "title": "" }, { "docid": "10063629", "text": "Rank-size distribution is the distribution of size by rank, in decreasing order of size. For example, if a data set consists of items of sizes 5, 100, 5, and 8, the rank-size distribution is 100, 8, 5, 5 (ranks 1 through 4). This is also known as the rank-frequency distribution, when the source data are from a frequency distribution. These are particularly of interest when the data vary significantly in scale, such as city size or word frequency. These distributions frequently follow a power law distribution, or less well-known ones such as a stretched exponential function or parabolic fractal distribution, at least approximately for certain ranges of ranks; see below.", "title": "" }, { "docid": "38873222", "text": "Marked Tree High School is a comprehensive public high school for students in grades 7 through 12 in Marked Tree, Arkansas, United States. Marked Tree is one of five public high schools in Poinsett County and is the only high school in the Marked Tree School District. Marked Tree High School is nationally recognized as a Bronze Medalist in the U.S. News & World Report Best High Schools ranking report. The school is accredited by AdvancED since 1965.", "title": "" }, { "docid": "1193571", "text": "Turn of the Tide (1935) is a British drama film directed by Norman Walker and starring John Garrick, Geraldine Fitzgerald, and Wilfrid Lawson, and was the first feature film made by J. Arthur Rank. Lacking a distributor for his film, Rank set up his own distribution and production company which subsequently grew into his later empire.", "title": "" }, { "docid": "333058", "text": "Doubleday is an American publishing company founded as Doubleday & McClure Company in 1897 that by 1947 was the largest in the United States. It published the work of mostly U.S. authors under a number of imprints and distributed them through its own stores. In 2009 Doubleday was merged with Knopf Publishing Group to form the Knopf Doubleday Publishing Group, which is now part of Penguin Random House.", "title": "" } ]

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